The "RADIANCE-HTN" Study. A Study of the ReCor Medical Paradise System in Clinical Hypertension
Phase: NA
Conditions: Hypertension, Vascular Diseases
Sponsor: ReCor Medical, Inc.

Confidential 
RADIANCE-HTN Clinical Study Protocol 
 
                                    ReCor Medical Confidential 
CLN-0777(C) 
 
 
 
 
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CLINICAL STUDY PROTOCOL 
 
 
 
The “RADIANCE-HTN” Study 
A study of the ReCor Medical Paradise System in Clinical Hypertension 
 
  
Protocol Number:  
CLN 0777 
 
 
 
Sponsor:  
ReCor Medical Incorporation / ReCor Medical BV / ReCor Medical, Ltd. 
 
1049 Elwell Court 
 
 
Palo Alto, CA 94303  
 
USA  
 
 
 
 
 
 
 
 
 
Current Version:  
 
Version C 
Release Date:  
 
October 11, 2019 
 
NCT 02649426 
 
ReCor Medical Inc. 
1049 Elwell Court 
Palo Alto, CA 
94303 
USA 
CONFIDENTIAL – This document 
contains confidential information that is the 
property of ReCor Medical Inc.  It may not 
be reproduced or disclosed without the 
express written consent of ReCor Medical. 
ReCor Medical BV. 
Keizersgracht 482 
1017EG 
Amsterdam,  
The Netherlands 
ReCor Medical, Ltd. 
46 Innovation House 
Discovery Park, 
Innovation Way 
Sandwich, Kent CT13 9FF 
United Kingdom 

Confidential 
RADIANCE-HTN Clinical Study Protocol 
 
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CLN-0777(C) 
 
 
 
 
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Revision History 
Revision Number 
Release Date 
Description 
A  
September 21, 2015 
Initial Release 
A 
November 15, 2015 
Initial Release- editorial updates 
A 
December 11, 2015 
Initial Release- FDA updates 
B 
July 13, 2018 
Clarification regarding Cross-Over process; addition of revised 
treatment strategy; Study PI change 
C 
October 11, 2019 
• Addition of 3.5mm balloon size and update to renal artery 
diameter size eligible for treatment 
•  Clarification of treatment strategy with addition of treatment 
strategy example figures  
• Addition of 4 & 5 Year follow-up visits;  
• Addition of Observational Efficacy endpoints for evaluation of 
blood pressure at all follow-up timepoints; 
• Update of company contact information 
• Update the radiation exposure risk to include the potential 
teratogenic damage, if pregnant 
• Correction of typographical errors and minor clarifications. 
 
 
 

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Contact Information 
Role 
Contact 
Author 
Helen Reeve-Stoffer PhD 
VP, Clinical Affairs 
ReCor Medical Inc. 
1049 Elwell Court 
Palo Alto, CA 94303 
E-mail: hreeve-stoffer@recormedical.com 
Tel: +44 (0) 794 774 8006 
Medical Affairs and 
Regulatory Contact 
Leslie Coleman, DVM 
VP Regulatory and Medical Affairs 
ReCor Medical Inc. 
1049 Elwell Court 
Palo Alto, CA 94303 
E-mail: LColeman@recormedical.com  
Tel: +1 650-542-7702 
Scientific Advisor 
Neil Barman, MD 
Chief Scientific Officer 
ReCor Medical Inc. 
1049 Elwell Court 
Palo Alto, CA 94303 
E-mail: NBarman@recormedical.com  
Tel: +1 650- 
Coordinating 
Principal Investigator 
(US) 
Dr. Ajay Kirtane, MD SM 
Columbia University Medical Center/New York-Presbyterian Hospital and the 
Cardiovascular Research Foundation,  
New York, NY, USA 
Coordinating 
Principal Investigator 
(OUS) 
Professor Michel Azizi, MD PhD 
Professor of Vascular Medicine, Hypertension Dept. and Clinical Investigation Center  
Hôpital Européen Georges Pompidou  
20-40 rue Leblanc, 75015 Paris, France 
Steering Committee 
Dr Michael Weber, MD FACP, FACC, FAHA, 
Professor of Medicine, SUNY Downstate College of Medicine, Brooklyn, NY, USA 
Dr Jan Basile, MD FACP 
Professor of Medicine, MUSC, Charleston, SC, USA 
Dr Michael Bloch MD 
Hypertension Specialist. Renown Regional Medical Center, Reno, NV, USA 
Dr Joost Daemen, MD PhD  
Cardiologist, Erasmus Medical Center, Rotterdam, The Netherlands 
Dr. Andrew Sharp, MD 
Cardiologist, Royal Devon and Exeter Hospital, Exeter, UK 
Dr. Melvin Lobo, MD PhD 
Director Barts’ BP Centre of Excellence, Barts’ NIHR Biomedical Research Centre, 
London, UK 
Dr Felix Mahfoud, MD PhD  
Cardiologist, University Hospital Saarlandes, Homburg/Saar, Germany 
Professor Roland Schmieder, MD  
Professor of Internal Medicine, University Hospital Erlangen, Erlangen, Germany 

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ReCor Medical 
Authorized 
Representative 
MedPass S.A.S 
95 bis, Boulevard Pereire 
75017 Paris, France 
Tel: +33 (0)1.42.12.28.84 
Fax: +33 (0)1.42.12.28.83 
ReCor Medical, Ltd.  
ReCor Medical, Ltd. 
46 Innovation House 
Discovery Park, Innovation Way 
Sandwich, Kent CT13 9FF 
United Kingdom 
+44 1304 806862 
ReCor Medical BV 
ReCor Medical, BV. 
Keizersgracht 482 
1017EG 
Amsterdam, The Netherlands 
 
 
 

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1. 
Study Summary _____________________________________________________ 10 
2. 
Introduction ________________________________________________________ 22 
 
Hypertension and Clinical Need _____________________________________________________ 22 
 
Other Therapeutic Options _________________________________________________________ 22 
 
Role of the Sympathetic Nervous System _____________________________________________ 22 
 
Percutaneous Renal Denervation Therapy _____________________________________________________ 23 
 
Prior Renal Denervation Clinical Evidence _____________________________________________ 23 
 
Symplicity HTN-1 and HTN-2 ________________________________________________________________ 23 
 
Symplicity HTN-3 _________________________________________________________________________ 24 
 
The Renal Denervation for Hypertension (DENERHTN) Trial _______________________________________ 24 
3. 
Summary of ReCor Medical Studies _____________________________________ 25 
 
Paradise Clinical Study Summary ____________________________________________________ 25 
 
The REDUCE Study ________________________________________________________________ 25 
 
The REALISE Study ________________________________________________________________ 26 
 
The ACHIEVE Study _______________________________________________________________ 27 
 
The RADIANCE-HTN Study (on-going) _________________________________________________ 27 
4. 
The Paradise® Renal Denervation System ________________________________ 28 
 
Device System Overview ___________________________________________________________ 28 
 
Main Components of the Paradise System ____________________________________________ 29 
 
The Paradise Catheter _____________________________________________________________________ 29 
 
The Paradise Generator ____________________________________________________________________ 31 
 
The Paradise Cartridge _____________________________________________________________________ 32 
 
Non-investigational Components of the Paradise System ________________________________ 33 
 
Sterile Water ____________________________________________________________________________ 33 
 
Guide Catheters __________________________________________________________________________ 33 
 
Guide Wires _____________________________________________________________________________ 33 
 
Hemostasis Valve _________________________________________________________________________ 33 
 
Principles of Operation ____________________________________________________________ 34 
 
System Labeling __________________________________________________________________ 34 
5. 
RADIANCE Study Purpose and Objectives _______________________________ 34 
 
Study Purpose ___________________________________________________________________ 34 
 
Study Objectives _________________________________________________________________ 35 
 
Primary Efficacy Endpoint __________________________________________________________________ 35 
 
Secondary Efficacy Endpoint ________________________________________________________________ 35 
 
Observational Efficacy Assessments __________________________________________________________ 35 
 
Safety Assessments _______________________________________________________________ 36 
 
Additional Safety Assessments ______________________________________________________________ 37 
6. 
Design _____________________________________________________________ 37 
 
Duration ________________________________________________________________________ 39 

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Treatment and Control Assignment __________________________________________________ 39 
 
Blinding ________________________________________________________________________ 39 
 
Cross-Over to Treatment ___________________________________________________________ 39 
 
Sample Size Rationale and Statistical Power ___________________________________________ 40 
 
Justification for the Study Design ____________________________________________________ 41 
 
RADIANCE Solo Cohort Justification __________________________________________________________ 41 
 
RADIANCE Trio Cohort Justification ___________________________________________________________ 42 
 
Justification for Efficacy Performance Criteria __________________________________________ 42 
 
Minimization of Risk ______________________________________________________________ 43 
7. 
Subject Selection ____________________________________________________ 43 
 
Study Population and Eligibility _____________________________________________________ 43 
 
Inclusion Criteria _________________________________________________________________ 43 
 
Inclusion Criteria - RADIANCE Solo ___________________________________________________________ 44 
 
Exclusion Criteria - RADIANCE Solo Cohort _____________________________________________________ 44 
 
Inclusion Criteria - RADIANCE Trio Cohort _____________________________________________________ 45 
 
Exclusion Criteria - RADIANCE Trio Cohort _____________________________________________________ 45 
7.2.4.1. 
Secondary Hypertension ______________________________________________________________ 47 
8. 
Subject Accountability ________________________________________________ 48 
 
Point of Enrollment _______________________________________________________________ 48 
 
Re-Consent ______________________________________________________________________ 48 
 
Withdrawal _____________________________________________________________________ 48 
 
Subject Status and Classification ____________________________________________________ 48 
9. 
Methods ___________________________________________________________ 49 
 
Visit schedule ____________________________________________________________________ 49 
 
V0: Study Screening Visit___________________________________________________________ 53 
 
RADIANCE Solo Cohort _____________________________________________________________________ 53 
 
RADIANCE Trio Cohort _____________________________________________________________________ 53 
 
V1: Baseline Eligibility Visit _________________________________________________________ 53 
 
Baseline ABP Review and Final Eligibility Testing ________________________________________________ 54 
 
Additional Pre-Procedure Testing ____________________________________________________________ 54 
 
P1. Hospitalization for Renal Denervation or Blinded (Sham) Procedure _____________________ 55 
 
Blinding Process __________________________________________________________________________ 55 
 
Hypertensive Medications Pre-Procedure _____________________________________________________ 55 
 
Procedural Medications ____________________________________________________________________ 56 
 
Diagnostic Renal Angiogram (all subjects) _____________________________________________________ 56 
 
Randomization ___________________________________________________________________________ 57 
 
Blinded (Sham) Procedure __________________________________________________________________ 57 
 
Renal Denervation Procedure _______________________________________________________________ 57 
 
Data Collection ___________________________________________________________________________ 60 
 
Post Procedural Pain Assessment ____________________________________________________________ 60 
 
D1. Hospital Discharge ____________________________________________________________ 61 

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In Clinic Follow-up Visits ___________________________________________________________ 61 
 
V2: One month Visit (30±7 days post procedure) ________________________________________________ 61 
 
V3: Two Month Primary Efficacy Endpoint Visit (60±7 days post procedure) __________________________ 62 
 
V4: Three Month Visit (90±7 days post procedure) ______________________________________________ 62 
 
V5: Four Month Visit (120±7 days post procedure) ______________________________________________ 63 
 
V6: Five Month Visit (150±7 days post procedure) _______________________________________________ 63 
 
V7: Six Month Visit (180±7 days post procedure) ________________________________________________ 63 
 
V8: Twelve Month Visit (360±14 days post procedure) ___________________________________________ 64 
 
V9, V10, V11 & V12: Twenty-Four (720±30), Thirty-Six (1080±30), Forty-Eight (1440±60) & Sixty (1880±60) 
Month Visits ____________________________________________________________________________________ 65 
 
Cross-Over to Treatment ___________________________________________________________ 65 
 
Cross-Over Data Collection _________________________________________________________________ 65 
 
Unscheduled Visits _______________________________________________________________ 68 
 
Study Completion ________________________________________________________________ 68 
 
Extended Follow-up Period _________________________________________________________ 68 
 
Study Closure ____________________________________________________________________ 68 
 
Study Medication ________________________________________________________________ 68 
 RADIANCE Solo Cohort Study Medication ______________________________________________________ 69 
 RADIANCE Trio Cohort Study Medication ______________________________________________________ 69 
 
Medication Changes due to BP Emergency ____________________________________________ 70 
 Low BP Action ____________________________________________________________________________ 70 
 High BP Action ___________________________________________________________________________ 71 
10. 
Study Defined Procedures/Testing ______________________________________ 71 
 
Office Blood Pressure Measurements ________________________________________________ 71 
 
24-hour ABP Measurements ________________________________________________________ 72 
 
Home BP Measurements___________________________________________________________ 72 
 
Standardized eGFR Calculation ______________________________________________________ 73 
 
Non-Invasive Imaging (CTA/MRA) ___________________________________________________ 73 
 
Non-Invasive Imaging (Renal Duplex Ultrasound) _______________________________________ 73 
 
Laboratory Assessments ___________________________________________________________ 74 
 
HP LC-MS/MS of Antihypertensive Compliance _________________________________________ 74 
 
Plasma Biomarkers- Optional Assessment _____________________________________________ 74 
11. 
Data Collection and Statistical Analysis __________________________________ 74 
 
Data Collection, Processing, and Review ______________________________________________ 74 
 
Statistical Analysis ________________________________________________________________ 75 
 
Primary Efficacy Endpoint __________________________________________________________ 75 
 
Secondary Efficacy Endpoint ________________________________________________________ 76 
 
Safety Assessments _______________________________________________________________ 76 

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Observational Assessments ________________________________________________________ 76 
 
Control of Systematic Error/Bias ____________________________________________________ 76 
 
Limits on Subjects Enrollment_______________________________________________________ 76 
 
Planned Interim Analyses __________________________________________________________ 77 
 Subgroup Analyses _______________________________________________________________ 77 
 Multivariable Analyses ____________________________________________________________ 77 
 Core Laboratories ________________________________________________________________ 77 
 Non-invasive Imaging Core Lab ______________________________________________________________ 77 
 Ambulatory Blood Pressure Core Lab (dabl Ltd) _________________________________________________ 77 
 Urine and Plasma Core Lab (CIC1418) _________________________________________________________ 78 
12. 
Safety Reporting _____________________________________________________ 78 
 
Definitions and Classification _______________________________________________________ 78 
 
Relationship to Study Device(s) or Procedure __________________________________________ 79 
 
ReCor Medical Device Deficiencies ___________________________________________________ 80 
Device Deficiency _______________________________________________________________________ 80 
 
Investigator Reporting Responsibilities _______________________________________________ 80 
 
Reporting to Regulatory Authorities / IRBs / ECs / Investigators ___________________________ 81 
 Sponsor Responsibilities ___________________________________________________________________ 81 
 Investigator Responsibilities ________________________________________________________________ 81 
13. 
Potential Risks and Benefits ___________________________________________ 81 
 
Risks Associated with the Study Device(s) _____________________________________________ 81 
 
Risks associated with Percutaneous Arterial Catheterization ______________________________ 83 
 
Risks Associated with Participation in the Clinical Study _________________________________ 84 
 
Risk Minimization Actions __________________________________________________________ 84 
 
Anticipated Benefits ______________________________________________________________ 85 
 
Risk to Benefit Rationale ___________________________________________________________ 85 
14. 
Protocol Deviations __________________________________________________ 86 
15. 
Protocol Amendments ________________________________________________ 86 
16. 
Device/Equipment Accountability _______________________________________ 87 
17. 
Compliance _________________________________________________________ 87 
 
Statement of Compliance __________________________________________________________ 87 
 
Investigator Responsibilities ________________________________________________________ 87 
 
Institutional Review Board/ Ethics Committee _________________________________________ 88 
 
Sponsor Responsibilities ___________________________________________________________ 88 
 
Insurance _______________________________________________________________________ 89 

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18. 
Monitoring _________________________________________________________ 89 
 
Study Monitor ___________________________________________________________________ 89 
 Monitoring Procedures ____________________________________________________________________ 89 
19. 
Informed Consent ___________________________________________________ 90 
 
Process of Obtaining Informed Consent _______________________________________________ 90 
20. 
Committees/Boards __________________________________________________ 91 
 
Adverse Event Review _____________________________________________________________ 91 
 
Data Safety Monitoring Board ______________________________________________________ 91 
 
Steering Committee ______________________________________________________________ 92 
21. 
Suspension or Termination ____________________________________________ 92 
 
Premature Termination of the Study _________________________________________________ 92 
 
Termination of Participation by Investigator/Withdrawal of IRB/ EC Approval _______________ 92 
 Requirements for Documentation and Subject Follow-up _________________________________________ 92 
 Criteria for Suspending/Terminating a Study Center _____________________________________________ 93 
22. 
Reporting and Publication Policy _______________________________________ 93 
23. 
Reimbursement and Compensation for Subjects ___________________________ 93 
24. 
Medicare Study Criteria (US Only) ______________________________________ 93 
25. 
Abbreviations and Definitions __________________________________________ 94 
 
Abbreviations ___________________________________________________________________ 94 
26. 
Appendix A: Visual Analog Pain Scale __________________________________ 95 
27. 
References _________________________________________________________ 96 
 
 
 

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1. Study Summary 
Introduction 
The ReCor Medical Paradise® Renal Denervation System (Paradise System) is a catheter-
based system that delivers ultrasound energy to thermally ablate and disrupt the renal efferent 
and afferent sympathetic nerves while sparing the renal arterial wall. The goal of renal nerve 
ablation is to achieve a reduction in sympathetic over-activity with the resultant effect of 
reducing systemic arterial blood pressure (BP), and mitigating resultant end organ damage.   
Study Purpose 
The purpose of the RADIANCE-HTN study is to demonstrate the ability of the Paradise System 
to effectively reduce systolic daytime ambulatory BP (ABP) in hypertensive subjects. In 
addition the study is designed to document the safety profile of the Paradise System in all 
treated subjects.  
Study 
Objective 
The objective of the RADIANCE-HTN study is to demonstrate the efficacy and verify the 
safety of the Paradise System in two distinct populations of hypertensive subjects. Prior to 
randomization, subjects will be hypertensive in the absence of hypertension medication or 
despite the presence of a stabilized, single pill, triple, fixed dose antihypertensive medication 
regimen. 
Study Design 
RADIANCE-HTN is a randomized, double-blind, sham controlled, 2-cohort study designed to 
demonstrate efficacy and document the safety of the Paradise Renal Denervation System in two 
distinct populations of hypertensive subjects.  
Patient 
Population 
Two study cohorts will be evaluated. Subjects with essential hypertension controlled on 1 or 2 
antihypertensive medications or uncontrolled on 0-2 antihypertensive medications will be 
included in the RADIANCE Solo cohort while subjects with treatment resistant hypertension 
on a minimum of 3 antihypertensive medications will be included in the RADIANCE Trio 
cohort.  
 
RADIANCE Solo Cohort 
After providing informed consent, subjects with uncontrolled (average seated office BP ≥ 
140/90 mmHg and < 180/110 mmHg mmHg) or controlled (average seated office BP <140/90 
mmHg) essential hypertension and currently prescribed to 1 or 2 antihypertensive medications 
will undergo a 4 week washout period of drug discontinuation. Drug discontinuation will occur 
in accordance with accepted, Institutional guidelines for the subjects’ current medication.  
Subjects currently not prescribed to any antihypertensive medication with an average seated 
office BP ≥ 140/90 mmHg and < 180/110 mmHg will undergo a 4 week run-in period.  After 4 
weeks, all subjects will undergo a 24 hour ABP measurement.  Those subjects whose daytime 
ABP  remains  ≥ 135/85 mmHg and <170/105 mmHg, will at a minimum undergo a baseline  
renal Computed Tomography Angiography (CTA) or Magnetic Resonance Angiography 
(MRA) to rule out renal abnormalities and/or significant renal artery stenosis if one is not 
already available that has been performed within one year prior to consent.  In addition, a 
baseline renal duplex ultrasound is strongly recommended (a duplex image documented within 
6 months of consent is also acceptable). Subjects with suitable renal artery anatomy on 
CTA/MRA will undergo a renal angiogram procedure. Subjects whose renal anatomy is re-
confirmed as suitable will then be randomized to renal denervation or blinded control 
(“sham”).* 
 
RADIANCE Trio Cohort 
After providing informed consent, subjects with uncontrolled, treatment resistant hypertension 
(average seated office BP ≥140/90 mmHg despite at least three antihypertensive drugs of 
different classes including a diuretic) will have their current hypertensive regimen replaced 

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with a single pill, triple, fixed dose antihypertensive combination of a calcium channel blocker 
(CCB), angiotensin II receptor blocker (ARB), and hydrochlorothiazide diuretic (HCTZ)** to 
be administered once daily during a  4 week stabilization period.  After 4 weeks, all subjects 
will undergo a 24-hour ABP measurement. Those subjects whose daytime ABP remains ≥ 
135/85 mmHg will at a minimum undergo a baseline renal CTA or MRA to rule out renal 
abnormalities and/or significant renal artery stenosis if not already performed within one year 
prior to consent. In addition, a baseline renal duplex ultrasound is strongly recommended (a 
duplex image documented within 6 months of consent is also acceptable). Subjects with a 
suitable renal artery anatomy on CTA/MRA will undergo a renal angiogram procedure. 
Subjects whose renal anatomy is re-confirmed as suitable will then be randomized to renal 
denervation or blinded control (“sham”).*  
 
*For those subjects randomized to blinded control, the renal angiogram will be considered the sham 
procedure 
**Options include Tribenzor/Sevikar HCT®; Olmesartan 40/HCTZ 25/Amlodipine 10 (Daiichi Sankyo); 
Exforge HCT®: Valsartan 160/HCTZ 25/Amlodipine 10 (Novartis) or generic Exforge HCT (TEVA 
Pharmaceuticals). Amlodipine doses may be reduced to 5mg in the event of disabling severe leg edema 
Note: Subjects with uncontrolled, treatment resistant hypertension currently prescribed to 
Tribenzor/Sevikar HCT or Exforge HCT (including generics) are eligible. Subjects will be followed for 
a 4 week stabilization period prior to confirming ABP according to the requirements of the protocol. 
Follow-Up 
Schedule Post 
Procedure 
The Primary Efficacy endpoint will be collected at 2 months post procedure in both cohorts; 
however, all subjects will be followed for a minimum of 60 months post procedure.  Scheduled 
in-clinic follow-up (FU) visits will occur at 1, 2, 3, 4, 5, 6, 12, 24, 36, 48 and 60 months post 
procedure.  All subjects will have seated office BP measurements taken at each clinic FU and 
24-hour ABP measurements will be taken at 2, 6 and 12 months post procedure.  Renal duplex 
ultrasound will be performed at baseline (recommended), 2, 6, 24 and 36 months post procedure 
and at any other time in the event there is clinical indication of post-denervation renal stenosis. 
A FU renal CTA or MRA will be performed 12 months after the procedure in all subjects that 
have been treated with renal denervation.  
Blood Pressure 
Measurements 
To limit variability in BP measurements, scheduled in-clinic visits should occur in the morning 
(preferably between 08:00 and 10:00am). Up to and including the 6 month FU visit, subjects 
should not take their study-defined antihypertensive medications on the day of the FU but rather 
bring their medication with them to the visit. Investigational sites may contact the subject before 
the scheduled visit to remind them.  Antihypertensive medications will then be taken during 
the FU after office BP measurements have been made and, when applicable, after ABP device 
set up.  Home BP measurements will be taken for the 7 days prior to each office FU (requiring 
a minimum of 18 BP measures to calculate a sustained average over 7 days).  
BP values recorded during this period will be used to assess any BP safety issues and determine 
hypertension medication escalation (see below) after the 2 month Primary Endpoint visit. 
Randomization 
Separate randomization schedules will be generated for the Solo and Trio Cohorts. The Trio 
randomization will be stratified by beta blocker use. A 1:1 randomization scheme will be used 
in both cohorts to assign subjects to treatment or blinded control (sham). Randomization will 
be generated by computer and stratified by center using blocks of small size and treatment 
permutation. Randomization will occur immediately following the renal angiogram to maintain 
subject blinding and to allow that subjects may be excluded prior to randomization for reasons 
of unsuitable renal anatomy.  

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Blinding 
The subjects and all study personnel taking FU BP measurements will be blinded to the 
randomization. Subjects will complete a blinding assessment1 prior to hospital discharge and 
at 2 and 6 months FU. All ABP measurements will be sent to a core lab.  
Changes in 
Anti-
hypertensive 
Medication 
For the period of wash-out/run-in (RADIANCE Solo) or stabilization (RADIANCE Trio) prior 
to the procedure, through to the 2-month Primary Efficacy endpoint visit, changes in medication 
outside the requirements of the study protocol may not occur, other than: 
• 
As required to facilitate antihypertensive drug wash-out per standard Institutional 
guidelines  
• 
In the incidence of a BP emergency (described below) 
• 
In the incidence of a clinical event that means a change in medication becomes 
necessary  
Following the 2-month Primary Efficacy endpoint visit, all subjects will remain blinded up to 
the 6 month visit. Between the 2 and 6 month FU visits, pre-defined escalation of 
antihypertensive medication is strongly recommended to be used in both cohorts. The 
medication escalation will start at the FU where a sustained elevation (≥ 135 mmHg systolic or 
≥ 85 mmHg diastolic) in 7-day home BP measurement is documented and subsequently 
confirmed by office BP ≥ 140 or ≥ 90 mmHg (if required per Institutional practice).  Drugs will 
be sequentially added in the event BP remains elevated at the current and subsequent FU visit. 
In the event BP remains <135/85 mmHg, no action is required. Unless medically 
contraindicated, introduction of each successive antihypertensive medication should occur 
sequentially in the order indicated below: 
RADIANCE Solo Cohort 
• 
Step 1- Add mid dose long acting dihdropyridine CCB (preferentially Amlodipine 5 
mg) 
• 
Step 2- Add full dose of long acting ARB (preferentially Valsartan 160-320 mg; or 
Olmesartan 20-40mg) or Angiotensin Converting Enzyme inhibitor (ACEi; 
preferentially Ramipril 10-20mg or  Lisinopril 20-40 mg) 
• 
Step 3- Add low dose of HCTZ (12.5 mg) 
• 
Step 4- Increase dose of  HCTZ  (25 mg) 
• 
Step 5-  Increase long acting dihydropyridine CCB to full dose (e.g. Amlodipine 10 
mg) 
Note: Doses are once daily 
Following the 6 month FU, subjects will be un-blinded and may have their medications 
modified per physician’s discretion. 
RADIANCE Trio Cohort (in addition to the single pill, triple fixed dose antihypertensive 
combination of Tribenzor/Sevikar HCT or Exforge HCT). 
• 
Step 1- Add Spironolactone (25-50 mg) 
 
1 Bang H, Ni L & Davis CE, Assessment of Blinding in Clinical Trials. 2004. Controlled Clinical Trials 25: 143-156 

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• 
Step 2-Add full dose of long acting, cardioselective Beta-1 receptor blocker 
(preferentially Bisoprolol 10 mg) 
• 
Step 3- Add full dose of central Alpha 2 receptor agonist (preferentially Clonidine 0.1-
0.2 mg, Rilmenidine 1-2mg or Moxonidine 0.2-0.4 mg) 
• 
Step 4- Add full dose of long-acting Alpha-1 receptor blocker (preferentially slow 
release Prazosin 5-10 mg or Doxazosin 4-8 mg) 
Note: Doses are once daily other than for Clonidine,  Rilmenidine or Moxonidine which should 
be added twice daily at their higher dosages 
Following the 6 month FU, subjects will be un-blinded and may have their medications 
modified per physician’s discretion. 
Medication 
changes due to 
Hypertensive 
or Hypotensive 
Emergency  
Since the aim of the RADIANCE-HTN study is to determine the effectiveness of renal 
denervation without medication changes confounding the results, it is intended that baseline 
hypertensive medication (or lack of it), be maintained through the Primary Efficacy endpoint 
visit which occurs two months after randomization. However in cases where medication 
changes are considered medically necessary (e.g. a significant change in BP or adverse events 
directly related to BP variations or BP medications), medication and/or doses may be adjusted 
according to the following guidelines: 
Low BP Action 
The dosage of study-defined drugs can be reduced temporarily or discontinued permanently for 
any subjects whose office systolic BP is reduced to <110mmHg with associated signs and 
symptoms of hypotension or reduced renal perfusion or an increase in plasma creatinine ≥ 30%. 
The order in which antihypertensive drugs should be discontinued will depend upon the 
subjects’ assigned cohort (Solo or Trio) and the stage that they are within the scheduled FU. 
For all subjects in whom hypertension medication escalation has started since the 2 month FU 
visit, down-titration or discontinuation of antihypertensive medication should follow the 
reverse order in which they have been added such that the last drug added should be first 
stopped (followed by the penultimate drug etc.). For subjects in the RADIANCE Trio cohort 
prescribed only to the single pill, fixed dose combination, reducing or stopping the current dose 
of HCTZ should be a first step with subjects then being switched to a double combination CCB 
+ ARB (Sevikar® or Exforge®).  All changes in antihypertensive treatment will be documented 
and patient BP data will be included as per intention-to-treat. 
High BP Action 
Clinical intervention may be required for patients who have clinical adverse events felt to be 
related to persistent or elevated hypertension at any visit after randomization defined by 7 day 
home BP ≥ 170 (systolic) or ≥ 105 mmHg (diastolic) and subsequently confirmed by office BP 
≥ 180 or ≥ 120 mmHg (if required per Institutional practice).  In these circumstances and 
assuming the subject is post-randomization, the treatment regimen should follow the 
hypertension medication escalation algorithm as described above.   
In the event that a hypertensive emergency is documented prior to randomization, the subject 
will be treated per Institutional guidelines and withdrawn from the study. 
All changes in antihypertensive treatment will be documented and patient BP data will included 
as per intention-to-treat. 

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Cross-Over to 
Treatment 
Following at least 6 months of FU post procedure, subjects assigned to the Control group may 
cross-over and receive treatment in the event that all of the following conditions are met: 
• 
The Primary Efficacy endpoint has been met in that patients’ cohort  
• 
The DSMB has not stopped the study due to safety concerns or indicated an increased 
safety risk associated with the treatment 
• 
The subject agrees to the procedure  
• 
The subject has an ambulatory daytime systolic ABP ≥ 135 and/or diastolic ABP ≥ 85 
mmHg 
 
In the event of cross-over to treatment, subjects will undergo a cross-over baseline evaluation, 
including review of key eligibility criteria, prior to the cross-over procedure. Subjects will then 
be followed at 1, 2, 6, 12, 24, 36, 48 & 60 months post cross-over procedure. 
Medication 
Compliance 
Compliance to the anti-hypertensive medication regimen will be assessed in the Trio cohorts 
by: 
• 
HP LC-MS/MS detection of antihypertensive drug metabolite by urine analysis 
Primary 
Efficacy 
Endpoint 
The Primary Efficacy endpoint will be the same in the two cohorts but analyzed separately; 
reduction in average daytime ambulatory systolic BP from baseline to 2 months post procedure. 
Primary 
Efficacy 
Endpoint 
Statistics  
The two cohorts will be analyzed independently for all endpoints. The average difference 
between randomized groups for the change in daytime ambulatory systolic BP at 2 months post-
procedure will be compared by ANCOVA adjusted for subjects’ baseline daytime ambulatory 
systolic BP. Tests will be performed separately for the RADIANCE Solo and RADIANCE Trio 
cohorts, each at a 0.05 alpha level as there is independent interest in conclusions for each cohort 
separately. For an assumed treatment effect (mean±standard deviation) of 6±12 mmHg, the 
planned sample size (n=292) will provide 80% power for each cohort based on a two-sided 
0.05 alpha and allows for no more than approximately10% of incomplete datasets and/or 
subjects to be lost to FU between randomization and the 2 month Primary Efficacy endpoint 
FU.  
Secondary 
Efficacy 
Endpoints 
• 
Reduction in average 24-hr/night-time ambulatory systolic BP at 2 months post procedure 
• 
Reduction in average daytime/24-hr/night-time diastolic BP at 2 months post procedure 
Observational 
Efficacy 
Assessments 
• 
Reduction in average office systolic/diastolic BP at 2, 6, 12, 24, 36, 48 and 60 months post 
procedure 
• 
Reduction in average daytime/24-hr/night-time ambulatory systolic BP at 6 and 12 months 
post procedure 
• 
Reduction in average daytime/24-hr/night-time ambulatory diastolic BP at 6 and 12 months 
post procedure 
• 
Reduction in average home systolic/diastolic BP at 2, 3, 4, 5 and 6 months post procedure 
• 
Incidence of ambulatory systolic BP (daytime/24-hr/night-time) reductions of ≥5 mmHg, 
≥10 mmHg, and ≥15 mm Hg at 2,  6 and 12 months post procedure 
• 
Percentage of subjects who are controlled in the absence of changes in hypertensive 
medication in each arm at 2, 6 and 12 months post procedure (daytime ABP <135/85 
mmHg;  night-time ABP < 120/70; 24-hr ABP< 130/80 mmHg; office BP <140/90 mmHg) 

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• 
Percentage of subjects who are controlled including any changes in hypertensive 
medication in each arm at 2, 6 and 12 months post procedure (daytime ABP <135/85 
mmHg;  night-time ABP < 120/70; 24-hr ABP< 130/80 mmHg; office BP <140/90 mmHg) 
• 
Change in office and ambulatory pulse pressure at 2, 6 and 12 months post procedure 
• 
Change in office and ambulatory heart rate at 2, 6 and 12 months post procedure 
• 
Changes in dipper/non-dipper patterns at 2, 6 and 12 months post procedure 
• 
Antihypertensive treatment score  (number of antihypertensive drugs, doses, classes) at 6 
and 12 months post procedure  
• 
Percentage of subjects requiring initiation of additional antihypertensive drug therapy 
between 2 and 6 months post procedure 
• 
Percentage of subjects without any antihypertensive treatment at 6 and 12 months post 
procedure in the RADIANCE Solo cohort 
• 
Compliance assessed by urine drug level determinations  
• 
Change in plasma biomarkers at 2 and 6 months post procedure (Solo cohort only, optional) 
• 
Percentage of patients in whom it is possible to deliver complete ablation profile (as 
determined by individual anatomy) 
Safety 
Assessments 
All adverse clinical events will be collected, coded and reported, for the duration of the study 
according to the definitions of ISO: 14155: 2011 (see Section 13.1).  
The occurrence rate for all the clinical events defined below will be calculated for each cohort, 
characterized by the DSMB and compared between and within arms (where applicable) for the 
duration of the study.  In addition, specific events within this list will also be reported as event 
rates within specific time frames post procedure.  
Events to be reported any time during the study: 
• 
All-cause mortality 
• 
Hypertensive emergency resulting in hospitalization 
• 
Hypotensive emergency resulting in hospitalization 
• 
Hospitalization for heart failure 
• 
Stroke, transient ischemic attack, cerebrovascular accident  
• 
Acute myocardial infarction (STEMI/non-STEMI) 
• 
Any coronary revascularization 
• 
End stage renal disease, the need for permanent renal replacement therapy (i.e. the need 
for dialysis); doubling of plasma creatinine 
• 
Any renal artery complication requiring intervention (e.g. dissection; perforation) 
• 
Major access site complications requiring intervention 
• 
Significant embolic events resulting in end organ damage 
• 
Procedure-related pain lasting for > 2 days  
• 
Acute renal injury, defined as: 
o Increase in plasma/serum creatinine by  ≥ 0.3 mg/dl (≥26.5 µmol/l) within 
48hrs of the procedure or, 
o Increase in serum/plasma creatinine to ≥1.5 times baseline known to have 
occurred during 7 days post procedure or, 
o Urine volume <0.5 ml/kg/h for 6 hours 

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• 
Significant (>50%) and severe (>75%)2 new onset renal stenosis as diagnosed by 
duplex ultrasound and confirmed by renal CTA/MRA or as diagnosed/confirmed by 
renal CTA/MRA 
• 
Need for renal artery angioplasty or stenting 
 
In addition, these specific events will also be reported as 1 month post procedure event rates: 
• 
Any renal artery complication requiring intervention (e.g. dissection; perforation) 
• 
Major access site complications requiring intervention 
• 
Significant embolic events resulting in end organ damage 
• 
Procedure-related pain lasting for > 2 days  
• 
Acute renal injury, defined as: 
o Increase in plasma/serum creatinine by  ≥ 0.3 mg/dl (≥26.5 µmol/l) within 
48hrs of the procedure or, 
o Increase in serum/plasma creatinine to ≥1.5 times baseline known to have 
occurred during 7 days post procedure or 
o Urine volume <0.5 ml/kg/h for 6 hours 
 
In addition, these specific events will also be reported as 6, 24 & 36 month post procedure 
event rates: 
• 
Significant (>50%) and severe (>75%) new onset renal stenosis as diagnosed by duplex 
ultrasound and confirmed by renal CTA/MRA or as diagnosed/confirmed by renal 
CTA/MRA 
• 
Need for renal artery angioplasty or stenting 
 
In addition, these events will be also reported as 12 months post procedure event rates: 
• 
Significant (>50%) and severe (> 75%) new onset renal stenosis as diagnosed by study-
defined renal CTA/MRA 
• 
Need for renal artery angioplasty or stenting 
Safety Design 
Justification 
This is the first randomized, blinded study evaluating the Paradise ultrasound technology and 
as such cardiovascular, device and procedural event rates are important determinants of the 
safety profile of the system. For this reason no pre-specified endpoint has been defined. To 
ensure that subjects are not inappropriately exposed to an increased risk of cardiovascular 
events including stroke and/or renal stenosis, the following measures have been included: 
• 
Drug discontinuation in the RADIANCE Solo cohort will occur in line with accepted 
Institutional guidelines for a subjects’ current medication and subjects’ whose baseline 
eligibility systolic/diastolic office BP is ≥180/110 mmHg or baseline daytime ABP is 
≥170/105 mmHg are excluded   
• 
Drug discontinuation in the RADIANCE Solo cohort is limited to a short period of 
approximately 3 months during which timeframe subjects are a low risk of any CV 
event off treatment3 
 
2 Hirsch A, et al., ACC/AHA 2005 Practice Guidelines for the management of peripheral arterial disease (lower extremity, renal, 
mesenteric and abdominal aortic) 2006. Circulation e465-e655 
3 DeFelice, A et al., 2008. The risks associated with short-term placebo-controlled antihypertensive clinical trials: a descriptive meta-
analysis. J Hum Hypertens. 22: 659-688 

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• 
All subjects will be provided with home BP monitoring devices from the point of a) 
drug discontinuation or run-in (RADIANCE Solo cohort) or b) initiation of fixed dose 
triple combination therapy (RADIANCE Trio Cohort)  
• 
Subjects whose average home BP increases to ≥170 mmHg systolic or ≥105 mmHg 
diastolic and who have clinical events considered to be related to persistent or elevated 
hypertension pre-randomization such that a change in medication is necessitated, will 
be excluded 
• 
Subjects whose average home BP increases to ≥170 mmHg systolic or ≥105 mmHg 
diastolic, post randomization will be eligible to have their anti-hypertensive medication 
restarted or modified as needed  
• 
Subjects in the RADIANCE Solo cohort will have anti-hypertensive drug therapy 
initiated immediately following the 2 month FU if needed  
• 
Non-invasive imaging will be required for all subjects at baseline (CTA/MRA at a 
minimum),  the 2 and 6 month FUs (duplex ultrasound) and for all treated subjects at 
the 12 month FU (CTA/MRA) and the 24 and 36 month FUs (duplex ultrasound) 
Additional 
Safety 
Assessments 
• 
Level of post-procedural pain as determined by the use of a Visual Analog Scale 
• 
Incidence of severe procedural pain defined as a score of ≥ 8 on the Visual Analog 
Scale 
• 
Incidence of new onset orthostatic hypotension post procedure 
• 
Change (reductions) from baseline in mean eGFR at 2, 6, & 12 months post-procedure 
• 
Change (increases) from baseline in mean plasma creatinine at 2, 6 & 12 months post-
procedure 
Pre-specified 
cohorts for 
analysis 
Post-hoc evaluations of efficacy will be evaluated in specific subgroups including but not 
limited to: 
• 
Gender 
• 
Ethnicity 
• 
Age  
• 
Baseline ABP 
• 
BMI 
• 
Geography 
• 
Number of ablations 
• 
Renal anatomy 
Overall Sample 
Size 
64 randomized subjects per arm were calculated as required to detect an absolute difference in 
daytime systolic ABP change from baseline to 2 months of 6 mmHg between Treatment and 
Control assuming a standard deviation of 12 mmHg, 80% power and a 2-sided 0.05 alpha. The 
estimated minimum sample size therefore to demonstrate efficacy is 128 subjects in each 
cohort. To account for an approximate 10% rate of premature withdrawal or failure to reach the 
primary end point measure, up to 146 subjects will be recruited and randomized into each 
cohort for a total sample size of 292 randomized subjects of which 146 will be treated.   
Study 
Geographies 
RADIANCE-HTN will be conducted at up to 40 clinical investigational sites in the USA and 
up to 40 sites outside the USA.   
Study Duration The expected duration, from enrollment to study closure, will be approximately 120 months. 

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Overall 
Subject 
Selection 
Subjects following the indications/contraindications for use of the Paradise System with a 
documented history of essential hypertension, will be identified from the general patient 
population by the enrolling center. In addition, subjects must meet all inclusion criteria and 
none of the exclusion criteria.  Minor differences in inclusion/exclusion criteria exist between 
the RADIANCE Solo and RADIANCE Trio cohorts reflecting the different stage in 
hypertension progression for each group.  Specific differences are shown in bold.  
Inclusion 
Criteria:  Solo 
Cohort 
Male and female subjects who meet the following criteria should be given consideration for 
inclusion in the Solo Cohort: 
 
• 
Appropriately signed and dated informed consent  
• 
Age ≥18 and ≤75 years at time of consent 
• 
Documented history of essential hypertension  
• 
Either,  
o Average seated office BP < 180/110 mmHg at screening visit (V0) while on a 
stable regimen of 1 or 2 antihypertensive medications for at least 4 weeks prior to 
consent or, 
o Average seated office BP ≥ 140/90 mmHg  <180/110 mmHg despite lifestyle 
measures on no antihypertensive medications 
• 
Documented daytime ABP ≥ 135/85 mmHg and < 170/105 mmHg after 4-week  
washout/run-in period  
• 
Suitable renal anatomy compatible with the renal denervation procedure and documented 
by renal CTA or MRA of good quality performed within one year prior to consent (a CTA 
or MRA will be obtained in patients without a recent (≤1 year) renal imaging)  
• 
Able and willing to comply with all study procedures  
Exclusion 
Criteria: Solo 
Cohort 
Subjects who meet any of the following criteria will be excluded from the Solo Cohort: 
• 
Renal artery anatomy on either side, ineligible for treatment including: 
o Main renal artery diameter < 4 mm and > 8 mm 
o Main renal artery length < 25 mm 
o A single functioning kidney  
o Presence of abnormal kidney (or secreting adrenal) tumors  
o Renal artery with aneurysm 
o Pre-existing renal stent or history of renal artery angioplasty 
o Prior renal denervation procedure 
o Fibromuscular disease of the renal arteries 
o Presence of renal artery stenosis of any origin ≥ 30% 
o Accessory arteries with diameter  ≥ 2mm <4 mm and > 8 mm* 
• 
Evidence of active infection within 7 days of procedure 
• 
Iliac/femoral artery stenosis precluding insertion of the Paradise Catheter 
• 
Type I diabetes mellitus or uncontrolled Type II diabetes (defined as a plasma Hb1Ac ≥ 
9.0%) 
• 
Documented history of chronic active inflammatory bowel disorders such as Crohn’s 
disease or ulcerative colitis eGFR of <40 mL/min/1.73 m2 (by Modification of Diet in 
Renal Disease formula) 
• 
Brachial circumference ≥ 42 cm 
• 
Any history of cerebrovascular event (e.g. stroke, transient ischemic event, cerebrovascular 
accident) 
• 
Any history of severe cardiovascular event (myocardial infarction, CABG, acute heart 
failure requiring hospitalization (NYHA III-IV) 
• 
Documented confirmed episode(s) of stable or unstable angina  

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• 
Documented repeat (>1) hospitalization for hypertensive crisis within the prior 12 
months 
• 
Prescribed to any standard antihypertensive of cardiovascular medication (e.g. beta 
blockers) for other chronic conditions (e.g. ischemic heart disease) such that 
discontinuation might pose serious risk to health  
• 
Documented history of persistent or permanent atrial tachyarrhythmia 
• 
Active implantable medical device (e.g. ICD or CRT-D; neuromodulator/spinal stimulator; 
baroreflex stimulator) 
• 
Chronic oxygen support or mechanical ventilation other than nocturnal respiratory support 
for sleep apnea. 
• 
Primary pulmonary hypertension 
• 
Documented contraindication or allergy to contrast medium not amenable to treatment 
• 
Limited life expectancy of < 1 year at the discretion of the Investigator 
• 
Any known, unresolved history of drug use or alcohol dependency, lacks the ability to 
comprehend or follow instructions, or for any reason in the opinion of the investigator, 
would be unlikely or unable to comply with study protocol requirements or whose 
participation may result in data analysis confounders (e.g. night shift workers) 
• 
Pregnant, nursing or planning to become pregnant (negative pregnancy test required, 
documented within a maximum of 7 days prior to procedure for all women of child bearing 
potential. Documentation of effective contraception is also required for women of child 
bearing potential)  
• 
Concurrent enrollment in any other investigational drug or device trial (participation in 
non-interventional Registries is acceptable) 
* This exclusion criteria may only be finally determined during the active renal angiogram procedure, 
subjects will therefore only count towards the enrollment ceiling at the time of randomization 
Inclusion 
Criteria:  Trio 
Cohort 
Male and female subjects who meet the following criteria should be given consideration for 
inclusion in the Trio Cohort: 
• 
Appropriately signed and dated informed consent 
• 
Age ≥18 and ≤75 years at time of consent 
• 
Documented history of hypertension  
• 
Average seated office BP ≥ 140/90 mmHg at screening visit (V0) while on a stable regimen 
of at least 3 antihypertensive medications of different classes including a diuretic for at 
least 4 weeks prior to consent 
• 
Documented daytime ABP ≥ 135/85 mmHg after 4-week stabilization period  
• 
Suitable renal anatomy compatible with the renal denervation procedure and documented 
by renal CTA or MRA of good quality performed within one year prior to consent (a CTA 
or MRA will be obtained in patients without a recent (≤1 year) renal imaging)  
• 
Able and willing to comply with all study procedures  
Exclusion 
Criteria: Trio 
Cohort 
Subjects who meet any of the following criteria will be excluded from the Trio Cohort: 
• 
Renal artery anatomy on either side, ineligible for treatment including: 
o Main renal artery diameter < 3 mm and > 8 mm 
o Main renal treatable artery length < 20 mm (may include proximal branching) 
o A single functioning kidney 
o Presence of abnormal kidney (or secreting adrenal) tumors  
o Renal artery with aneurysm 
o Pre-existing renal stent or history of renal artery angioplasty 
o Pre-existing aortic stent or history of aortic aneurysm 
o Prior renal denervation procedure 

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o Fibromuscular disease of the renal arteries 
o Presence of renal artery stenosis of any origin ≥ 30% 
o Accessory arteries with diameter ≥2 mm < 3 mm or > 8 mm* 
• 
Iliac/femoral artery stenosis precluding insertion of the Paradise Catheter 
• 
Evidence of active infection within 7 days of procedure 
• 
Secondary hypertension not including sleep apnea (documented through clinical 
work up within the 12 months prior to consent- see protocol body for details) 
• 
Type I diabetes mellitus or uncontrolled Type II diabetes (defined as a plasma Hb1Ac ≥ 
9.0%) 
• 
Documented history of chronic active inflammatory bowel disorders such as Crohn’s 
disease or ulcerative colitis  
• 
eGFR of <40 mL/min/1.73 m2 (by Modification of Diet in Renal Disease formula) 
• 
Brachial circumference ≥ 42 cm 
• 
Any history of cerebrovascular event (e.g. stroke, transient ischemic event, cerebrovascular 
accident) within 3 months prior to consent 
• 
Any history of severe cardiovascular event (e.g. myocardial infarction, CABG, acute heart 
failure requiring hospitalization (NYHA III-IV) within 3 months prior to consent 
• 
Documented repeat (>1) hospitalization for hypertensive crisis within the prior 3 months 
• 
Documented confirmed episode(s) of unstable angina within 3 months prior to consent 
• 
Documented intolerance or contraindication for any of the antihypertensive drugs 
prescribed as a requirement of the study protocol  
• 
Prescribed to any standard anti-hypertensive CV medication (other than beta blockers) 
for other chronic conditions (e.g. ischemic heart disease) such that discontinuation might 
pose serious risk to health  
• 
Documented history of persistent or permanent atrial tachyarrhythmia 
• 
Active implantable medical device (e.g. ICD or CRT-D; neuromodulator/spinal stimulator; 
baroreflex stimulator) 
• 
Chronic oxygen support or mechanical ventilation other than nocturnal respiratory support 
for sleep apnea. 
• 
Primary pulmonary hypertension 
• 
Documented contraindication or allergy to contrast medium not amenable to treatment 
• 
Limited life expectancy of < 1 year at the discretion of the Investigator 
• 
Any known, unresolved history of drug use or alcohol dependency, lacks the ability to 
comprehend or follow instructions, or for any reason in the opinion of the investigator, 
would be unlikely or unable to comply with study protocol requirements or whose 
participation may result in data analysis confounders (e.g. night shift workers) 
• 
Pregnant, nursing or planning to become pregnant (documented negative pregnancy test 
required documented within a maximum of 7 days prior to procedure for all women of child 
bearing potential. Documentation of effective contraception is also required for women of 
child bearing potential)  
• 
Concurrent enrollment in any other investigational drug or device trial (participation in 
non-interventional Registries is acceptable) 
 
* This exclusion criteria may only be finally determined during the active renal angiogram procedure, 
subjects will therefore only count towards the enrollment ceiling at the time of randomization 
Study 
Administration 
RADIANCE-HTN will be run under the guidance of a Steering Committee comprising of 
International physicians with expertise in the areas of renal denervation, Vascular Medicine, 
Hypertension, Interventional Cardiology and Nephrology. An independent Data Safety 

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Monitoring Board (DSMB) will also oversee the study activities from a safety perspective and 
pre-specified clinical events will be adjudicated by independent physicians. 
Ethics 
The study will be conducted in accordance with the declaration of Helsinki, ISO 14155:2011, 
FDA 21 CFR parts 50, 54, 56, 812 and other applicable local and national regulations.  
 
 

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2. Introduction 
 Hypertension and Clinical Need 
Hypertension is a major public health burden, present in more than one quarter of adults in developed 
societies and associated with reduced life expectancy and increased risk for cardiovascular disease, 
including myocardial infarction, stroke, and heart failurei,ii.  At present it accounts for approximately 9 
million deaths worldwide annuallyiii.  
Currently the first line treatments for hypertension are recommendations for lifestyle modification (e.g. 
dietary restrictions including salt, caffeine and alcohol; increased exercise and reduced smoking), and the 
use of antihypertensive medication.  Guidelines typically recommend the use of one or two drugs of 
different classesiv but despite the well documented ability of hypertensive drugs to reduce blood pressure 
(BP), particularly in combination,v hypertension remains uncontrolled in as much as 50% of patients in 
the United States with even higher rates in Europe. Uncontrolled hypertension may be caused by multiple 
factors including inadequate or inappropriate treatment, poor medication adherencevi,vii and in a subset of 
patients, hypertension which is truly non-responsive to conventional therapies- a condition known as 
resistant (or refractory) hypertension. The European Society of Hypertension defines resistant 
hypertension as BP that remains above goal despite treatment with a therapeutic plan that has included 
attention to lifestyle measures and the prescription of at least three drugs (including a diuretic) in adequate 
doses.iv Resistant hypertension has been estimated to affect 15% to 30% of participants in clinical trials 
of antihypertensive medication and 5% to 30% of patients in clinical practice.viii While the specific benefits 
of treating resistant hypertension compared with more easily controlled hypertension are not known, it is 
well-established that hypertension control as a means to prevent cardiovascular morbidity and mortality 
provides substantial clinical and economic benefit.ix  
 Other Therapeutic Options 
Currently therapeutic options outside the use of standard classes of antihypertensive medication are 
limited for patients with resistant hypertension.x Novel antihypertensive drug classes are being explored 
that may enhance options for patients resistant to multiple drug treatment, including direct renin inhibition 
(e.g., Aliskiren), centrally-acting sympatholytics (e.g., Clonidine & Rilmenidine), and selective endothelin 
receptor antagonists. However, the limitations of purely pharmacologic therapy for patients with resistant 
hypertension (e.g., treatment failure in a significant subset of patients, adherence challenges, side effects, 
and concerns regarding polypharmacy), have prompted the exploration of interventional approaches to 
provide complementary therapeutic tools.  
 Role of the Sympathetic Nervous System 
The etiology of resistant hypertension is likely multifactorial. However, animal studies and subsequent 
studies in humans have demonstrated that the sympathetic nervous system, in particular afferent and 
efferent sympathetic nerves from and to the kidneys, plays an important role in BP regulation and the 
pathophysiology of hypertension.xi,xii In certain patient subsets, activity of the afferent and efferent 
sympathetic nerves in the renal artery walls may be the primary mechanism by which the kidneys 
contribute to systemic hypertension.  
The disruption of activity in the renal nerves has been shown to prevent, delay, or reduce the magnitude 
of hypertension in a wide variety of animal models.xiii,xiv These results were extended to humans during 

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the mid-century through experience with surgical sympathectomy (splanchnicectomy), a major, invasive 
procedure that reduced BP at the cost of significant operative mortality, and which was abandoned with 
the advent of effective pharmacotherapy.xv Despite an unacceptable risk profile, surgical sympathectomy 
did demonstrate proof-of-concept for complete sympathetic denervation in the treatment of hypertension 
and set the stage for modern, more targeted, treatment modalities.xvi Amongst these are a therapeutic 
system for baro-reflex activation, which modifies afferent sympathetic nerve activity via stimulation of 
the carotid sinus nerves (the Rheos Baroreflex Hypertension Therapy System - CVRx Inc, Minneapolis, 
MN, USA), targeted injection of neurotoxic agents directly into the perivascular layer of the renal artery 
wall (e.g. Ablative Solutions PeriVascular Renal Denervation system, Menlo Park, CA, USA) and 
minimally invasive interventional approaches to renal sympathetic denervation therapy, accomplished via 
catheter-based percutaneous denervation procedures targeting the renal nerves in patients with resistant 
hypertension.xvii,xviii,xix,xx    
 Percutaneous Renal Denervation Therapy 
Disruption of the afferent and efferent sympathetic nerve bundles via a catheter-mounted probe was 
originally investigated as a treatment for resistant hypertension using radiofrequency (RF) energy. The 
original product for this indication was the Symplicity® Catheter System™ (Ardian Inc., Palo Alto, CA, 
USA), which received CE mark in Europe in 2008.  The device is powered by an external RF generator 
and consists of a catheter tipped with a 2mm electrode that delivers RF energy directly to the renal arterial 
wall at multiple discrete locations in an attempt to transmurally ablate focal sympathetic nerves. 
Subsequent to development of the original Symplicity Catheter System, other RF systems using the same 
general model of energy delivery have been developed including primarily the Vessix Renal Denervation 
System (Vessix Vascular, Inc. Laguna Hills, VA, USA) which consists of a non-compliant balloon 
catheter with bipolar electrodes mounted on the exterior of the balloon and the EnligHTN™ multi 
electrode Renal denervation system (St Jude Medical, St Paul, MN, USA).  The ReCor Medical Paradise 
renal denervation system is differentiated from these systems in that it uses ultrasound energy delivered 
circumferentially to the adventitia, thus sparing the renal arterial wall, while still ablating the sympathetic 
nerves 
 Prior Renal Denervation Clinical Evidence 
The primary clinical data supporting percutaneous RF renal denervation comes from studies evaluating 
the performance of the Symplicity Catheter Systemxvii,xviii,xix,xxi, although both the Vessixxxii and 
EnligHTNxxiii Systems have some level of clinical evidence supporting them. 
 Symplicity HTN-1 and HTN-2  
The initial Symplicity study (HTN-1) was a 50 patient, un-blinded, single arm, observational study 
designed to demonstrate proof-of-concept and was conducted at five centers in Europe and Australia.xvii 
The results from HTN-1 were based on average office BP measurements which were shown to be 
significantly lowered at 1, 3, 6, 9 and 12 months post treatment with a range of systolic BP drops from -
14 mmHg at 1 month to -27 mmHg at 12 months.  A follow-up publication on the long-term, 3-year data 
from the treated patients demonstrated that the treatment effect appeared to be sustained over time.xxiv 
Safety data supported that the procedure was low risk with only one renal artery dissection reported.   
The compelling data from the HTN-1 study was followed quickly by results from HTN-2 which was a 
non-blinded, randomized, placebo- controlled evaluation of the effect of the Symplicity catheter in 

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resistant hypertensive patients. The study enrolled 106 patients (52 randomized to renal denervation and 
54 to control) and the patients were followed for 6 and 12 months.  In line with the early data from HTN-
1, HTN-2 also documented substantial drops in office BP at 6 and 12 months (-32/-12 mmHg and -28/-10 
mmHg in the treatment group respectively) while the control group showed a small increase in BP at 6 
months (+7/+1 mmHg).xviii. In addition, Control patients who elected to cross-over after 6 months, also 
demonstrated significant drops of office BP following 6 months of treatment (-24/-8 mmHg). xix  However, 
despite the supposedly effective data being reported from the HTN-1 and 2 trials plus evidence from 
multiple observational studies including the large Global Symplicity Registry,xxv concerns were being 
voiced related to the strength of the data including the unprecedented size of the documented office BP 
drops, the lack of strict control over criteria for resistant hypertension, limited ambulatory BP (ABP) 
evidence and absence of blinding and sham control.xxvi,xxvii 
 Symplicity HTN-3 
In contrast to HTN-1 and HTN-2, the Symplicity HTN-3 trial was a randomized, blinded and sham- 
controlled safety and efficacy evaluation of the Symplicity catheter conducted at 88 US clinical centers.  
A total of 535 patients whose baseline office systolic BP was ≥160 mmHg despite stable treatment with 
maximum tolerated doses of at least 3 antihypertensive drugs including a diuretic, were randomized 2:1 
to renal denervation versus sham control with the sham consisting of a renal angiogram procedure.  The 
primary efficacy endpoint for HTN-3 was the change in office systolic BP at 6 months with a secondary 
endpoint related to change in mean 24-hr ambulatory systolic BP.xxviii The data from HTN-3 demonstrated 
that despite an office systolic BP drop at 6 months of -14.1 mmHg in the treatment arm, there was also a 
substantial average drop in BP in the sham arm of -11.7 mmHg, such that the difference between arms 
was not statistically significant. A similar trend was observed with ABP data where the actual difference 
in systolic BP drop between arms was < 2mmHg.xxix  Despite the lack of significant effectiveness of the 
treatment versus a sham procedure, the safety endpoint was passed with no documented difference in 
safety risk between groups as defined per protocol.  The outcome of the HTN-3 trial was unprecedented 
based on early data from HTN-1 and 2 and has resulted in substantial discussions related to the appropriate 
design and implementation of future renal denervation clinical trials.xxx,xxxi  
 The Renal Denervation for Hypertension (DENERHTN) Trial 
Recently a French Ministry of Health-sponsored study of the Symplicity Catheter (DENERHTN) was 
published in Lancetxxxii evaluating the effect of RF renal denervation in hypertensive patients uncontrolled 
on a standardized, stepped-care, antihypertensive treatment regimen versus patients uncontrolled on the 
same standardized hypertensive treatment alone.  The trial was double blind and placebo-controlled and 
was designed and conducted by clinical centers in France specialized in hypertension management. 
Initially patients were stabilized for 4-6 weeks on a fixed dose, triple combination antihypertensive 
regimen consisting of Indapamide (1.5 mg), Amlodipine (10 mg) and Ramipril 10 mg or Irbesartan (300 
mg). If patients remained hypertensive on this therapy regimen, they were then randomized 1:1 to renal 
denervation or standardized therapy alone.  A total of 1416 patients were screened to enroll and randomize 
106 patients. Approximately half of 1416 screened patients were excluded due to the documented presence 
of clinical causes of secondary hypertension.  Patients were initially followed for 6 months with monthly 
in-office visits and monitoring of home BP. A predefined antihypertensive medication escalation protocol 
was in place for both groups so that drug burden could be evaluated at 6 months post randomization and 
to ensure that patients were not allowed to remain hypertensive for extended periods of time. The primary 
endpoint of the study was a difference in daytime ABP between groups with office and home BP 

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differences as secondary analyses. At 6 months, DENERHTN demonstrated that the mean decrease in 
daytime systolic ABP was statistically greater in patients randomized to renal denervation plus 
standardized therapy versus standardized therapy alone.  In addition, the percentage of patients controlled 
at the 6 month FU visit, was higher in the renal denervation group for daytime, night-time and 24-hr ABP. 
DENERHTN is currently the only blinded, placebo-controlled, evidence demonstrating significant effect 
of renal denervation in resistant hypertension and its design is likely to provide important insight into key 
factors to be considered when designing future evaluations of renal denervation.  
3. Summary of ReCor Medical Studies 
 Paradise Clinical Study Summary 
First in human evidence of the clinical safety and efficacy of the Paradise System was initially evaluated 
in the first-in-man REnal Denervation by Ultrasound transCatheter Emission (REDUCE) Trial, a single-
center feasibility study initiated in 2011 and conducted at Vergelegen Medi-Clinic, South Africaxxxiii. 
Subsequently, two multi-center, ReCor Medical Inc. sponsored post-market evaluations (the REALISE 
and ACHIEVE studies) were initiated in 2012, and 2013, respectively. 
 The REDUCE Study 
Patients enrolled in the REDUCE study were diagnosed with resistant hypertension as defined by the 2007 
European Society of Hypertension and the European Society of Cardiology, with a minimum BP of 140/90 
mmHg (office), 135/85 mmHg (home) and 130/80 mmHg (ambulatory) despite being treated with at least 
three antihypertensive medications including a diuretic.  Patients under the age of 18 years, pregnant, 
allergic to contrast media, or with any known cause of secondary hypertension were excluded. A CT-scan 
was performed at screening to further exclude patients with vascular abnormalities (including renal artery 
stenosis and iliac or femoral artery stenosis precluding insertion of the Paradise catheter) or not meeting 
the anatomical criteria (renal artery of more than 20 mm in length and 4 mm in diameter).   
Fifteen patients with resistant hypertension underwent renal denervation in the REDUCE study. All 
patients met the ESH-ESC criteria for resistant hypertension at baseline. Patients took, on average, 4.1 
antihypertensive medications, with 100% receiving diuretics, 87% calcium-channel blockers, and 87[% 
angiotensin-converting enzyme inhibitors.  The mean age of enrolled patients was 52 years; 40% were 
male.  Baseline co-morbidities and cardiovascular risk factors included diabetes (20%), history of angina/ 
myocardial infarction (33%), history of stroke (20%) and one patient had a history of obstructive sleep 
apnea.  The average office blood pressure at baseline was 182±22/110±15 mmHg and average baseline 
24-hour ambulatory blood pressure was 173±19/102±16 mmHg. A 12-French treatment catheter with 8 
mm balloon was used for the first three cases, while the subsequent 12 subjects were treated with a 6 
French catheter with either a 6 mm or 8 mm balloon. Up to three ultrasound emissions were delivered in 
each renal artery at variable energies and with variable cooling flow rate. The majority of emissions were 
for 50 seconds (range 14-55). Eight patients were treated with low cooling flow of either 8ml/minute (n=5) 
or 5 ml/minute (n=3).  Of those patients treated with low cooling flow, two developed clinically significant 
renal artery stenosis noted at their 6-month FU visit, requiring angioplasty and stenting. One additional 
patient developed renal artery stenosis beyond the 6-month visit which was treated with angioplasty.   The 
stenoses were attributed to inadequate cooling of the renal arterial wall.  Accordingly, the cooling flow 
rate was increased to 41-50 ml/minute for all subsequent procedures in REDUCE, as well as for all future 
clinical use of the Paradise System 

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Pretreatment, mean office systolic BP was 182±22 mmHg (n=15), and mean 24-hour ambulatory systolic 
BP was 173±19 mmHg (n=13).  Following bilateral treatment with the Paradise System, reductions in 
office systolic BP were observed by 3 months (-27.4±26.2) and sustained through 6 and 12 months, (-32.7 
±27.3 at 6 months and -28.9±32.2 at 12 months).  Similarly, meaningful reductions in ambulatory systolic 
BP were observed at 3 months (-9.7±15.2) 6 months (-13.6±14.8) and 12 months (-6.9±15.5).   
Pain (back; abdominal; groin) associated with the procedure was reported in 9/15 patients (60%).  A total 
of five device-related events requiring intervention were reported:  three cases of stenosis discussed above; 
one case of procedural renal artery dissection caused by a guide wire; and one case of significant 
vasospasm requiring angioplasty.  One patient experienced a hypertensive crisis requiring hospitalization 
within 30 days of the procedure.   The patient was stabilized with medication and discharged within 24 
hours with no further reports of hypertensive crisis. 
In summary the REDUCE study was designed to document the safety and effectiveness of the Paradise 
System in the setting of a first-in-man feasibility study.  There have been significant changes implemented 
to the Paradise System based on the REDUCE experience. 
 The REALISE Study 
The REALISE Study was designed as an adjunct confirmatory clinical study based on the REDUCE 
protocol to further evaluate the Paradise System.   The study was a single-arm, open label prospective 
study conducted in France at two clinical sites to evaluate the Paradise System in patients with moderate 
resistant hypertension defined by the 2007 ESH/ESC guidelines. Per the guidelines, patients were required 
to have a baseline office BP >140/90 mmHg despite the use of a minimum of 3 antihypertensive 
medications, including a diuretic on maximally tolerated doses.  All patients enrolled in the study were 
managed by a multi-disciplinary team which included a hypertension specialist. The majority of patients 
were on 5 anti-hypertensive medications at baseline, and 70% of patients were taking Spironolactone at 
baseline.   
Enrollment in the REALISE study was completed in March 2014.  One year FU on all patients was 
completed on March 21, 2015.  The mean age of enrolled patients was 54 years; 70% were males.  Baseline 
comorbidities and cardiovascular risk factors included type II diabetes mellitus (45%), history of 
peripheral vascular disease (35%), history of stroke (30%), history of myocardial infarction (30%), history 
of obstructive sleep apnea (30%), and prior renal denervation (5%). The mean office systolic BP at 
baseline was 168±19 mmHg (n=19), and mean ambulatory systolic BP at baseline was 157±14 mmHg 
(n=20).  Following bilateral treatment with the Paradise System, reductions in office systolic BP were 
observed by 3 months (-7.4±28.2) and sustained through 6 and 12 months (-10.5±33.6 at 6 months, and -
16.6±27.2 at 12 months).  Similarly, meaningful reductions in ambulatory systolic BP were observed at 6 
months (-7.8±17.4) and 12 months (-5.2±12.7.  In addition, post treatment, the mean antihypertension 
medication burden decreased from 5.4 to 4.4 with an overall reduction in medication burden of 21%. 
System related safety events were minimal with none requiring intervention or hospitalization.  These 
included back pain (n=9); non-specific abdominal pain (n=1), mild access related vascular injury (n=1) 
and minor intimal dissection in the left renal artery during the procedure that did not require intervention 
(n=1).  Safety events beyond 30 days included renal complications defined as worsening pre-existing renal 
failure (n=2), thromboembolic event (stroke 5 months post procedure, n=1) and death (11 months post 
procedure due to pneumococcal meningitis, n=1). There have been no reports of new onset renal artery 
stenosis.  

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In summary, The REALISE study demonstrated a reduction in office and ABP sustained through 12 
months following treatment with the Paradise System in patients with moderate resistant hypertension 
despite optimal medical management, including Spironolactone, in the majority of patients. 
 The ACHIEVE Study  
 The TrAnsCatHeter Intravascular ultrasound Energy delivery for rEnal denervation (ACHIEVE study) 
was a post market study that enrolled patients with severe resistant hypertension at eight sites in Sweden, 
Germany, and the Netherlands.   Ninety-six (96) subjects were treated and followed for 12 months.    
Measurement of office BP was required at 3, 6 and 12 month FU visits and optional at 1 month. Recordings 
of 24-hr ABP was required at a minimum, for all patients at 6 and 12 months post treatment.  The mean 
age of enrolled patients was 64 years and 59% were male.  Baseline comorbidities and cardiovascular risk 
factors included type II diabetes mellitus (40%), history of peripheral vascular disease (8%), history of 
stroke (10%), history of myocardial infarction (24%), history of obstructive sleep apnea (21%), and prior 
renal denervation (1%). The mean office systolic BP at baseline was 176±21 mmHg (n=95) and mean 24-
hr ABP at baseline was 156±15 mmHg (n=91).  Ninety-five (95) patients completed the 3 months FU, 92 
completed 6 months FU and 87 completed 12 months FU. Results in the Intention to Treat (ITT) 
population demonstrate a mean systolic office BP drop of -15 mmHg at 12 months (n=80, P<0.001).  In 
the same population, mean 24-hr ABP drops were -7 mmHg at 12 months (n=76, P< 0.0007). During the 
study there was a single patient with an event meeting the MAE definition: a hospitalization for 
hypertensive crisis within 1 month of the procedure.   Of note, within 1 month of the procedure there were 
no cases of mortality, renal failure (eGFR < 15 or need for dialysis), embolic event resulting in end-organ 
dysfunction, renal perforation or dissection requiring intervention, or access site complication requiring 
repair or transfusion.  There were also no cases of new stenosis > 70% within 6 months.  Five of 96 patients 
(5.2%) had minor groin complications not meeting the MAE definition.   In the entire study follow-up 
there was one patient death due to a presumed myocardial infarction approximately 3 months after the 
procedure; this event was deemed to be unrelated to the device or procedure.   
 The RADIANCE-HTN Studyxxxiv (on-going) 
The SOLO cohort of the RADIANCE-HTN Study completed recruitment on December 28th 2017. The 
TRIO cohort is ongoing and includes subjects with resistant hypertension who have had their current 
antihypertensive medication replaced by a single pill, triple, fixed-dose antihypertensive medication 
regimen.   
In the SOLO cohort, a total of 146 subjects were randomized to renal denervation (N=74) or sham 
procedure (renal angiogram) (N=72). In the Intention to treat (ITT) population, renal denervation reduced 
daytime ambulatory systolic blood pressure more than the sham procedure (-8.5 mm Hg vs. -2.2 mm Hg; 
baseline-adjusted difference: -6.3 mm Hg, 95% CI -9.4 to -3.1, P<0.001). Consistent reductions were 
observed for daytime diastolic, and 24-hr ambulatory systolic and diastolic BPs. Fewer subjects in the 
renal denervation group received antihypertensive medication prior to 2 months compared with the sham 
group [5/74 (6.8%) vs. 13/72 (18.1%), P=0.04]. Among subjects in the renal denervation group, 15/74 
(20.3%) attained controlled 2-month daytime ambulatory BP (<135/85 mm Hg) in the absence of 
antihypertensive medications, vs. 2/72 (2.8%) in the sham group (P=0.001). A per protocol analysis was 
also completed which excluded the following subjects: 1) subjects not meeting baseline daytime ABP or 
renal anatomy inclusion criteria, 2) subjects in the denervation group who did not receive bilateral 
denervation, 3) subjects we were treated with antihypertensive medication before the 2-month ABP 

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measurement and 4) subjects who did not compete the 2-month ABP assessment.  By removing these 
confounding, especially those of antihypertensive medication restarts. The per protocol differences are 
even larger (daytime between group 2-month ambulatory systolic difference of -8.2 mm Hg; P<0.001)xxxv.   
No major adverse events have been reported in either the Treatment or Control arms in the RADIANCE-
HTN SOLO Cohort to date. 
4. The Paradise® Renal Denervation System  
 Device System Overview 
The ReCor Medical Paradise® Renal Denervation System (Paradise System) is CE-marked in countries 
accepting the CE mark, but Investigational in the USA.  
The system is a catheter-based device designed to use ultrasound energy to thermally ablate the afferent 
and efferent nerves surrounding the renal artery and serving the kidney. Key features which differentiate 
ultrasound energy from RF energy are: 
• Direct tissue contact with the ultrasound energy source is not required for energy transmission, 
minimizing the risk of overheating the arterial wall with consequent tissue damage 
• The absorption of ultrasound by liquids (including blood) is minimal, thereby potentially 
avoiding the risk of thrombogenicity that may occur when a RF energy source loses contact 
with the vessel wall  
• Ultrasound provides controlled energy delivery independent of catheter positioning or tissue 
characteristics 
• Ultrasound provides a controllable ablation profile via manipulation of duration and intensity 
of the energy delivery combined with changes in cooling flow rate 
• The uniform circumferential heating possible with ultrasound reduces the number of treatment 
sites required to achieve renal nerve ablation, minimizing energy delivery and improving ease 
of use 
The Paradise System consists of two main components: a single use Paradise Catheter, containing an 
ultrasound energy source (transducer) and a portable Paradise Generator, which powers the transducer.  
The Paradise Catheter is introduced via femoral access under fluoroscopic guidance and advanced into 
the renal artery.  Bilateral renal denervation is achieved by delivering ultrasound energy within each renal 
artery. 
The Paradise System also includes two ancillary components allowing the delivery of fluid and power to 
the main components, all of which are used within the scope of their labeling: 
• Paradise Cartridge when used in conjunction with the Generator, controls the closed-loop 
cooling fluid flow through the Catheter 
• Paradise Connection Cable allows for the communication of transducer information, such as 
operating frequency and serial number, from the Catheter to the Generator as well as the transfer 
of electrical energy during the procedure 
 
Table 4.1-1, identifies the components of the Paradise System and their basic attributes. 
 

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Table 4.1-1: Paradise System Components 
Identification Paradise System (PRDS) Component 
Sterile 
Reusable 
Blood 
Contact 
PRDS-063-02 
PRDS-064-02 
PRDS-065-02 
PRDS-066-02 
PRDS-067-02 
PRDS-068-02 
PRDS Catheter (3.5 mm balloon diameter) 
PRDS Catheter (4.2 mm balloon diameter) 
PRDS Catheter (5 mm balloon diameter) 
PRDS Catheter (6 mm balloon diameter) 
PRDS Catheter (7 mm balloon diameter) 
PRDS Catheter (8 mm balloon diameter) 
Yes 
No 
Yes 
PRDS-USG-02 
Paradise Generator 
No 
Yes 
No 
PRDS-CC-02 
Paradise Cartridge 
Yes 
No 
No 
PRDS-CT-02 
Paradise Connection Cable  
Yes 
No 
No 
 
 Main Components of the Paradise System 
 The Paradise Catheter 
The Paradise Catheter consists of a single use, multi-lumen catheter shaft with a cylindrical piezoelectric 
ceramic transducer inside an inflatable balloon at the distal end of the catheter.  The cylindrical transducer 
converts the electrical energy to ultrasound energy, which is then radiated into the renal artery tissue.  
Located at the proximal end of the catheter, is a hub that connects electrical and fluid pathways.  The 
Paradise Catheter (Figures 4.2-1 & 4.2-2) is available in 3.5, 6, 7 and 8 mm balloon sizes. 
 
 
 

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Figure 4.2-1:  The Paradise Catheter with Magnified Detail of Ultrasound Source 
 
 
 
 
 
 
 
 
Figure 4.22-2. Paradise Catheter Features 
 
Transducer 
Balloon 
Catheter Shaft 
Cooling Water
 

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Each Paradise Catheter has a programmed memory chip (EEPROM) that communicates to the Paradise 
Generator to automatically set the power level (Watts) and frequency (MHz) required to treat various 
diametric sizes of renal arteries.  The physician selects the Paradise Catheter with appropriate balloon size 
based on measuring the renal artery size using standard medical angiographic techniques.  
 The Paradise Generator 
The Paradise Generator is designed to control energy delivery and fluid management of the Paradise 
System to ensure proper therapy.  The Paradise Generator contains all of the electronics and fluid controls 
for the device as well as a user interface on the front panel.  On the Paradise Generator front panel, the 
user can control all operating stages of the Paradise System, including catheter balloon inflation and 
deflation, and initiating or discontinuing therapy.  The duration of energy delivery is programmed into the 
Paradise Generator software and is not a parameter that can be changed by the user.  Each Catheter’s 
power level (Watts) and the Generator’s duration (seconds) is what comprises the Paradise System energy 
dose. 
The Generator interfaces with a Paradise Cartridge to provide sterile fluid to the Catheter for inflating and 
deflating the catheter balloon and aiding in the delivering of the therapy.  The Paradise Generator is 
connected to the Paradise Catheter through the Paradise Cartridge and the Paradise Connection Cable.  
Electrical energy is delivered from the Generator through the Catheter, at which point, the electrical energy 
is converted to ultrasound energy via a piezoelectric transducer.  Ultrasound energy is then transferred 
into the renal artery tissue which converts to heat and denervates the renal artery nerves safely and 
effectively.   
 
Figure 4.2-3 below illustrates the Paradise Generator and accessories with its components identified.  
Figure 4.2-3.  Paradise Generator and Accessories 
 
 

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The Paradise Cartridge attaches to the Generator and the Catheter.  The Cartridge manages the flow of 
sterile water and the monitors the pressure within the catheter’s balloon.  The monitored pressure is 
communicated to the Paradise Generator and the Generator will adjust fluid flow to maintain accurate 
catheter balloon pressure throughout all of the System operating stages.  
 The Paradise Cartridge 
The Paradise Cartridge is an accessory that is designed to support the procedural needs and functional 
operation of the Paradise System.  When the Paradise Cartridge is used in conjunction with the Paradise 
Generator, it controls the sterile fluid flow into and out of the Paradise Catheter in a close-loop system.  
The fluid flows through the Cartridge and the Catheter body to the balloon at the catheter’s distal tip and 
returns to the Cartridge.  The integrated tubing is comprised of two distinct lumens and is 3 meters in 
length.  The integrated tubing connects the Cartridge to the catheter’s proximal end.  The connectors at 
the Cartridge’s distal end are reversible so that the orientation of connection to the catheter is universal. 
The Paradise Cartridge attaches to the Generator and the Catheter.  The Cartridge manages the flow of 
sterile water and the monitors the pressure within the catheter’s balloon.  The monitored pressure is 
communicated to the Paradise Generator and the Generator will adjust fluid flow to maintain accurate 
catheter balloon pressure throughout all of the System operating stages.  Figure 4.2-4 illustrates the 
Paradise Cartridge. 
Figure 4.2-4. Paradise Cartridge Diagram  
 
The Paradise Connection Cable (as shown in Figure 4.2-5) provides the electrical connectivity between 
the Generator and the Catheter. 
Figure 4.2-5. Paradise Connection Cable Diagram 
 

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 Non-investigational Components of the Paradise System 
 Sterile Water 
Sterile water is required that can be connected to the Paradise Cartridge. The following water is 
recommended for use: 
 
• Baxter 2B0304 Sterile Water for Injection (1000 ml) 
• Wasser für Testzwecke et190 (Austria) 
• B Braun Ecobag 75/12610321/0111  
• B Braun L8500 (1000 ml) 
 Guide Catheters 
The Paradise Catheter is introduced into the body using a commercially available guide catheter of 
minimum internal diameter 0.081” and 55 cm length. The following Guide Catheters are recommended 
for use: 
• Medtronic Launcher RDC tip (7 or 8 French; 55 cm) 
• Medtronic MP1 ((7 or 8 French; 55 cm) 
• Medtronic IMA (7 or 8 French; 55 cm) 
• Medtronic SCR (7 or 8 French; 55 cm) 
• Cordis Vista Brite-Top RDC (7 or 8 French; 55 cm) 
• Terumo Destination® Guiding Sheath (6 French; 45 cm) 
 
The following Guide Catheters should not be used: 
• Boston Scientific Mach 1 series (7 or 8 French) 
 Guide Wires 
Any 0.014”, 190 cm, heavy or middle weight commercially available guide wire may be used with the 
Paradise Catheter.  The following guide wires are specifically recommended for use: 
• Abbott Vascular Balance Middleweight (BMW) 
• Abbott Vascular Balance Heavyweight (BHW) 
• Cordis ATW 
• Biotronik Galeo M 
• Abbott Spartacore 14 
 
Note: Guidewires with floppy distal tips are not recommended. 
 Hemostasis Valve 
A non-threading hemostasis valve is necessary to ensure appropriate catheter sterile water flow.  The 
following hemostasis valve is required for optimal Paradise System function: 
• Merit Medical Honor hemostasis valve (P/N MAP300) 

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 Principles of Operation 
The Paradise System utilizes therapeutic ultrasound energy consisting of high-frequency sound waves (i.e. 
rapid mechanical oscillations) that generate frictional heating in soft tissues.  Due to the physics of sound 
propagation, direct tissue contact with the ultrasound source is not required for energy transmission.  
Therefore, a balloon-based fluid transfer mechanism is implemented for cooling the endothelial and 
medial layers of the arterial wall to preserve the integrity of the arterial wall during the energy delivery 
process.  The Paradise System utilizes a cylindrical ultrasound source (the transducer) which creates 
uniform toroidal lesions with controllable geometries.  By optimizing the size, shape and location of the 
lesion, denervation can be maximized while protecting the arterial intimal and medial layers.  
The target thermal profile for energy delivery includes near-field and far-field cooled zones, to minimize 
endothelial or medial cell damage and to ensure there is no damage to non-target tissues beyond the 
targeted tissue region. The target ablation zone is located approximately 1-6 mm from the arterial lumen 
where the accumulated thermal dose rises sufficiently to achieve cell death.   Optimization of the tissue 
thermal profile can be achieved through management of the power delivered to the transducer, the duration 
of energy delivery, and the cooling flow rate.   
The Paradise Catheter is intended to be employed in a catheterization laboratory under fluoroscopic 
guidance via femoral access only. The catheter is deployed into the renal artery through a delivery catheter 
inserted into the femoral artery near the groin and advanced to the descending aorta.  
 
The Paradise Catheter is a minimally invasive device, remaining inside the body, in contact with the blood 
and the blood vessel walls for the duration of a typical catheterization laboratory procedure (less than one 
hour). It is supplied sterile and intended for a single use. 
Appropriate systemic anticoagulation should be administered prior to procedure and verified by ACT or 
similar testing (e.g., ACT of 200, 250, or 300s depending on local guidelines). There are no specific post-
treatment recommendations. 
 System Labeling 
The Paradise System is CE-marked and labelled for “renal denervation” in countries accepting the CE 
mark for use, but is Investigational in the United States.  
For this clinical study, the Paradise System will display the following labelling, as required by United 
States regulation: 
CAUTION:  Investigational device. Limited by Federal (or United States) law to 
investigational use. 
 
5. RADIANCE Study Purpose and Objectives 
 Study Purpose 
The purpose of the RADIANCE-HTN study is to demonstrate the ability of the ReCor Medical Paradise 
System to effectively reduce systolic daytime ABP in hypertensive subjects. In addition, the study is 
designed to document the safety profile of the Paradise System in all treated subjects 

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 Study Objectives 
The objective of the RADIANCE-HTN study is to demonstrate the efficacy and verify the safety of the 
Paradise System in two distinct populations of hypertensive subjects. Prior to randomization, subjects will 
be hypertensive in the absence of hypertension medication or despite the presence of a stabilized, single 
pill, triple, fixed dose antihypertensive medication regimen. Study endpoints have been formulated to 
support these objectives. 
 Primary Efficacy Endpoint 
The Primary Efficacy endpoint will be the same in the two cohorts but analyzed separately; reduction in 
average daytime ambulatory systolic BP at 2 months post procedure.  
 Secondary Efficacy Endpoint 
The Secondary efficacy endpoints will be: 
• Reduction in average 24-hr/night-time ambulatory systolic BP at 2 months post procedure 
• Reduction in average daytime/24-hr/night-time diastolic BP at 2 months post procedure 
 Observational Efficacy Assessments 
The following observational assessments will also be documented:  
• Reduction in average office systolic/diastolic BP at 2, 6, 12, 24, 36, 48 & 60 months post procedure 
• Reduction in average daytime/24-hr/night-time ambulatory systolic BP at 6 and 12 months post 
procedure 
• Reduction in average daytime/24-hr/night-time ambulatory diastolic BP at 6 and 12 months post 
procedure 
• Reduction in average home systolic/diastolic BP at 2, 3, 4, 5 and 6 months post procedure 
• Incidence of ambulatory systolic BP (daytime/24-hr/night-time) reductions of ≥5 mmHg, ≥10 
mmHg, and ≥15 mm Hg at 2, 6 and 12 months post procedure 
• Percentage of subjects who are controlled in the absence of changes in hypertensive medication in 
each arm at 2, 6 and 12 months post procedure (daytime ABP <135/85 mmHg; night-time ABP < 
120/70; 24-hr ABP< 130/80 mmHg; office BP <140/90 mmHg) 
• Percentage of subjects who are controlled including any changes in hypertensive medication in each 
arm at 2, 6 and 12 months post procedure (daytime ABP <135/85 mmHg; night-time ABP < 120/70; 
24-hr ABP< 130/80 mmHg; office BP <140/90 mmHg) 
• Change in office and ambulatory pulse pressure at 2, 6 and 12 months post procedure 
• Change in office and ambulatory heart rate at 2, 6 and 12 months post procedure 
• Changes in dipper/non-dipper patterns at 2, 6 and 12 months post procedure 
• Antihypertensive treatment score (number of antihypertensive drugs, doses, classes) at 6 and 12 
months post procedure  

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• Percentage of subjects requiring initiation of additional antihypertensive drug therapy between 2 and 
6 months post procedure 
• Percentage of subjects without any antihypertensive treatment at 6 and 12 months post procedure in 
the RADIANCE Solo cohort 
• Compliance assessed by urine drug level determinations  (Trio Cohort) 
• Change in plasma biomarkers at 2 and 6 months post procedure (Solo Cohort, optional) 
• Percentage of patients in whom it is possible to deliver complete ablation profile (as determined by 
individual anatomy) 
 Safety Assessments  
All adverse clinical events will be collected, coded and reported, for the duration of the study according 
to the definitions of ISO: 14155: 2011 (see Section 13.1).  
The occurrence rate for all the clinical events defined below will be calculated for each cohort, 
characterized by the DSMB and compared between and within arms (where applicable) for the duration 
of the study.  In addition, specific events within this list will also be reported as event rates within specific 
time frames post procedure.  
Events to be reported any time during the study: 
• All-cause mortality 
• Hypertensive emergency resulting in hospitalization 
• Hypotensive emergency resulting in hospitalization 
• Hospitalization for heart failure 
• Stroke, transient ischemic attack, cerebrovascular accident  
• Acute myocardial infarction (STEMI/non-STEMI) 
• Any coronary revascularization 
• End stage renal disease, the need for permanent renal replacement therapy (i.e. the need for 
dialysis); doubling of plasma creatinine 
• Any renal artery complication requiring intervention (e.g. dissection; perforation) 
• Major access site complications requiring intervention 
• Significant embolic events resulting in end organ damage 
• Procedure-related pain lasting for > 2 days  
• Acute renal injury, defined as: 
o Increase in plasma/serum creatinine by ≥ 0.3 mg/dl (≥26.5 µmol/l) within 48hrs of the 
procedure or, 
o Increase in serum/plasma creatinine to ≥1.5 times baseline known to have occurred during 
7 days post procedure or 
o Urine volume <0.5 ml/kg/h for 6 hours 
• Significant (>50%) and severe (>75%)4 new onset renal stenosis as diagnosed by duplex 
ultrasound and confirmed by renal CTA/MRA or as diagnosed/confirmed by renal CTA/MRA 
 
4 Hirsch A, et al., ACC/AHA 2005 Practice Guidelines for the management of peripheral arterial disease (lower extremity, renal, 
mesenteric and abdominal aortic) 2006. Circulation e465-e655 

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• Need for renal artery angioplasty or stenting 
 
In addition, these specific events will also be reported as 1 month post procedure event rates: 
• Any renal artery complication requiring intervention (e.g. dissection; perforation) 
• Major access site complications requiring intervention 
• Significant embolic events resulting in end organ damage 
• Procedure-related pain lasting for > 2 days  
• Acute renal failure, defined as: 
o Increase in plasma/serum creatinine ≥ 0.3 mg/dl (≥26.5 µmol/l) within 48hrs of the 
procedure or, 
o Increase in serum/plasma creatinine to ≥1.5 times baseline known to have occurred during 
7 days post procedure or 
o Urine volume <0.5 ml/kg/h for 6 hours 
 
In addition, these specific events will also be reported as 6, 24 & 36 months post procedure event rates: 
• Significant (>50%) and severe (>75%)xxxiv new onset renal stenosis as diagnosed by duplex 
ultrasound and confirmed by renal CTA/MRA or as diagnosed/confirmed by renal CTA/MRA 
• Need for renal artery angioplasty or stenting 
 
In addition, these specific events will be also reported as 12 months post procedure event rates: 
• Significant (>50%) and severe (> 75%) new onset renal stenosis as diagnosed by study-defined 
renal CTA/MRA 
• Need for renal artery angioplasty or stenting 
 
 Additional Safety Assessments  
The following observational assessments will also be documented: 
• Level of post-procedural pain as determined by the use of a Visual Analog Scale (see Appendix 
A) 
• Incidence of severe procedural pain defined as a score of ≥ 8 on the Visual Analog Scale 
• Incidence of new onset orthostatic hypotension post procedure 
• Change (reductions) from baseline in mean eGFR at 2, 6, & 12 months post-procedure 
• Change (increases) from baseline in mean plasma creatinine at 2, 6 & 12 months post-procedure 
6. Design 
The RADIANCE-HTN Study is a multi-center, randomized, double-blind, sham controlled, 2-cohort 
study designed to demonstrate efficacy and document safety of the Paradise System in two distinct 
populations of hypertensive subjects. The study will be conducted in up to 40 clinical investigational sites 
in the USA and up to 40 sites outside of the USA.  

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Figure 5.3-1: RADIANCE-HTN Study Design 
e 
Informed Consent 
Solo Cohort  
Drug Wash-out/Run-in 
Period 
Trio Cohort 
Stabilization Period 
Screening Failure 
*allowable in the event of invalid dataset/technical failure 
Screening for 
Eligibility and 
Office BP review 
24-hr ABP  
CTA or MRA 
(if needed) 
Diagnostic 
renal 
angiogram 
1 Repeat*  
e
Home BP Review 
Screening Failure 
For the definitions of Screening Failure, Intent & Attempt 
see Section 8.3. 
Renal Duplex 
Ultrasound** 
(if needed) 
Attempt  
Treatment  
Control 
1, 2, 3, 4, 5, 6, 12, 24 & 36 months 
Does not meet Protocol-defined eligibility 
Meets Protocol-defined eligibility 
Office BP Review 
**recommended 
Screening Failure 
1, 2, 3, 4, 5, 6, 12, 24, 36, 48 & 60 months 

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Duration 
The RADIANCE-HTN Study will include up to 292 randomized subjects who will be followed 
in accordance with the study protocol for 60 months post procedure. It is anticipated that the 
duration of the study will be approximately 120 months. Figure 5.3-1 documents the study flow. 
 
Treatment and Control Assignment 
The RADIANCE-HTN Study is a randomized study requiring treatment and blinded control 
assignments in both the Solo and Trio Cohorts.  Subjects meeting all the inclusion criteria and 
none of the exclusion criteria will be assigned in a 1:1 (Treatment: Blinded Control) scheme.  
Subjects will be considered to count towards the enrollment ceiling at the point of 
randomization independent of whether they undergo a successful procedure or not (see Section 
8.3 for subject classifications).   
 
Blinding 
All subjects will be blinded up to the 6 Month FU. Specifically: 
• Subjects will be blinded during the procedure by ensuring sedation occurs prior to 
randomization. In addition, unless the subject is under general anesthesia, headphones 
and eye covers will be used. Other methods such as standardization of length of time 
spent in cath lab for blinded controls, removal of clocks in recovery room and 
prevention of contact between subjects treated on the same day may be considered. 
 
• A blinding indexxxxvi will be used to evaluate the success of subject blinding. The 
blinding index will be evaluated post-procedure but prior to discharge and also at 2 and 
6 months FU. 
Study personnel responsible for the measurement and upload of ABP post randomization will 
be blinded. To ensure patient safety, it is strongly recommended that the pre-discharge 
evaluation be completed by un-blinded site personnel aware of the details of the procedure.  To 
reduce the potential for bias, it is strongly recommended that site personnel blinded to a 
subjects’ randomization continue to be responsible for blood pressure measurements even after 
the patient is un-blinded at the 6-month follow-up. Blinding is further defined in the 
RADIANCE-HTN Blinding & Emergency Un-blinding Process Document (CLN-0029). 
 
The Sponsor will be blinded to the Primary Efficacy Endpoint data which will be handled 
directly through the ABP core lab and independent statistician. Due to the nature of their support 
role, Sponsor representatives may be un-blinded to a limited number of randomization due to 
presence at Procedures and/or during monitoring (see Sections 17.4 and 18.1).  In the event of 
device deficiency, adverse device effects or serious adverse device effects the Sponsor may 
become aware of the randomization of a specific subject but there will be no connection to 
outcome primary Efficacy data.   The DSMB will be blinded to all primary efficacy data unless 
specific criteria for un-blinding are met. 
 
Cross-Over to Treatment 
Following at least 6 months of FU post procedure, subjects randomized to the Control group 
may cross-over and receive treatment in the event that all of the following conditions are met: 
• The Primary Efficacy endpoint has been met in that patients’ cohort  

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• The DSMB has not stopped the study due to safety concerns or indicated an increased safety 
risk associated with the treatment 
• The subject has an ambulatory daytime systolic BP ≥ 135 and/or diastolic BP ≥ 85 mmHg* 
• The subject agrees to the procedure  
• At time of cross-over, the patient does not meet any of the following exclusion criteria: 
o Renal and/or renal artery anatomical exclusion criteria 
o Evidence of active infection within 7 days of procedure 
o Iliac/femoral artery stenosis precluding insertion of the Paradise Catheter 
o Type I diabetes mellitus or uncontrolled Type II diabetes (defined as a plasma 
Hb1Ac ≥ 9.0%)** 
o Any cerebrovascular event (e.g. stroke, transient ischemic event, cerebrovascular 
accident) within 3 months prior to cross-over baseline visit (COV1)  
o Any severe cardiovascular event (myocardial infarction, CABG, acute heart failure 
requiring hospitalization (NYHA III-IV) within 3 months prior to cross-over 
baseline visit (COV1) 
o Documented confirmed episode(s) of stable or unstable angina within 3 months 
prior to cross-over baseline visit (COV1) 
o Hospitalization for hypertensive crisis within the 3 months prior to cross-over 
baseline visit (COV1) 
o Active implantable medical device (e.g. ICD or CRT-D; neuromodulator/spinal 
stimulator; baroreflex stimulator) 
o Pregnant, nursing or planning to become pregnant (negative pregnancy test required, 
documented within a maximum of 7 days prior to procedure for all women of child 
bearing potential).  
 
*Up to 2 ABPM recordings may be performed to confirm eligibility with no more than 6 weeks between 
recordings. 
** Results from the tests performed as part of the most recent study follow-up visits may be used unless there are 
major changes to the patient condition or treatment.  
 
Sites will be informed by the Sponsor at the point that a cross-over becomes an option. Subjects 
that cross-over to treatment will be followed according to the cross-over visit schedule (see 
Table 9.1-2).  
More frequent FU than those specified above are at the discretion of the Investigator and will 
be documented as unscheduled visits. 
 
Sample Size Rationale and Statistical Power 
The sample size for the study is based on a desire to compare randomized groups separately for 
each cohort at the point of the Primary Efficacy Endpoint. Calculations are based on evaluating 
the treatment versus control groups for 1) the RADIANCE Solo and 2) RADIANCE Trio 
cohorts) independently.  
 
Statistical analyses will be performed separately for the RADIANCE Solo and RADIANCE 
Trio cohorts, each at a two-sided 0.05 alpha level as there is independent interest in conclusions 
for each cohort separately. Conservatively, sample size calculations are based on a two-sample 
t-test. The planned analysis with the adjustment for baseline should provide additional power 
beyond this, but the precise level depends on the correlation of the baseline value with the 
reduction during FU. Based on a two-sample t-test, for an assumed mean±standard deviation 
difference of 6±12 mmHg, a planned evaluable sample size of 128 subjects per cohort will 

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provide 80% power. These calculations can be confirmed with the following SAS System 
(version 9.3) code: 
 
 
proc power; 
 
twosamplemeans test=diff 
 
meandiff = 6  
 
stddev = 12 
 
alpha = 0.05 
 
power = 0.80 
 
ntotal = . ; 
 
run; 
 
To account for the loss of power due to missing data at the 2 month FU visit, an approximate 
10% inflation is used so the total randomized per cohort is planned at 146 subjects, or 292 total. 
 
Justification for the Study Design 
The recent Simplicity HTN-3 pivotal trial.xxvii, xxix was able to demonstrate safety of RF renal 
denervation in drug resistant hypertensive patients, but unable to demonstrate efficacy.  
Subsequent evaluation of the data, indicate that one major confounder of the outcome may have 
been patient compliance to the drug regimen, a complex phenomenon well documented in the 
pharma literature.vi,vii There is also evidence that despite the initial belief that the severely 
resistant hypertensive patient population may be the appropriate target for renal denervation, 
the pathophysiology of these patients may not make them amenable to any attempts to reduce 
BP particularly because of the incidence of endothelial dysfunction, inflammation and extreme 
arterial stiffness.xxxvii,xxxviii For these reasons, and understanding that blood pressure is a 
continuous variable, RADIANCE-HTN has been designed to evaluate the effect of renal 
denervation in two valid but distinct patient cohorts that may respond differently to renal 
denervation.  
 RADIANCE Solo Cohort Justification 
The “RADIANCE Solo” cohort which will be treated in the absence of any antihypertensive 
drugs will allow the evaluation of renal denervation without the confounding influence of drugs 
either from a pharmacological or patient compliance perspective. Moreover, these patients tend 
to be younger with higher sympathetic nervous system activity than patients with more severe 
resistant hypertensionxxxix suggesting that they may be more susceptible to renal denervation. 
Additionally, the arterial wall in younger, less severely hypertensive patients may be more 
responsive to renal denervation-induced changes in sympathetic tone since vascular 
remodelling is still in a reversible state. Indeed, the high prevalence of target organ damage in 
patients with resistant hypertension, including renal fibrosis and vascular stiffness which are 
difficult to reverse, renders BP control difficult to achieve whatever methods are used. Finally, 
the potential that pill burden may be reduced subsequent to successful renal denervation, might 
be of particular benefit in this younger population The evaluation of antihypertensive therapy 
in a “drug-free” cohort has precedence in the pharmaceutical industry and the patient population 
has been defined to minimize risk of cardiovascular events including stroke. The time that 
RADIANCE Solo cohort patients will be taken off their antihypertensive medications is limited 
specifically in line with the short-term study designs typically used to evaluate new 
antihypertensive therapy against placebo control.  On the basis of the Placebo in Hypertension 
Adverse Reaction Meta-analysis Project,xl the risks associated with such placebo-controlled 
study designs appear justified particularly in light of the positive safety profile (immediate, mid-

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term and long-term vascular safety) so far documented from more than 3000 renal denervation 
procedures performed world-wide with RF catheters and more than 200 procedures with the 
Paradise Catheter. 
 RADIANCE Trio Cohort Justification 
The “RADIANCE Trio” cohort will allow evaluation of the effect of renal denervation in the 
more traditional resistant hypertension patients (per the definition of at least 3 antihypertensive 
drugs including a diuretic) but with the added advantages of using a single, pill, fixed 
combination triple combination of a CCB, ARB and hydrochlorothiazide diuretic (HCTZ). 
Since there remains a real barrier to diagnosing resistant hypertension because of 1) the failure 
of healthcare providers to appropriately increase and/or change a patients therapeutic regimen 
(known as clinical or therapeutic inertiaxli) and 2) a well-documented inverse relationship 
between adherence and the number of antihypertensive drugs that a patient is required to 
takexlii,xliii there is a real possibility that unless appropriately managed, patients in the 
RADIANCE Trio cohort may have poorly controlled rather than resistant hypertension.   The 
use of a single-pill triple-combination antihypertensive therapy is likely to improve adherence 
and hence increase the probability of documenting controlled BP in patients who are not 
actually resistant. While this may require a larger screening population in order to enroll the 
required number of subjects, it is likely that the population that will be more homogenous and 
with a higher probability of being actually uncontrolled on three antihypertensive drugs. There 
is some evidence that subjects with increased incidence of endothelial dysfunction, 
inflammation and extreme arterial stiffness may not be amenable to renal denervation control 
of BP.xxxvi,xxxvii With that in mind, the inclusion/exclusion criteria of the study have been 
designed to minimize inclusion of subjects with substantial arterial stiffness. 
 
The study design aims to establish that within 2 months of randomization, either one or both, 
of these subject cohorts will respond to renal denervation with a reduction in daytime ABP that 
is significantly different between treated and blinded control subjects (sham).  The use of ABP 
for the efficacy endpoints is designed to reduce the placebo effect and variability often 
associated with the use of office BP.  The study design of evaluating multiple subject cohorts 
within the realms of a single study has general precedence in the pharmaceutical industry where 
it is frequently used to test multiple drug combinations and/or doses within a single study.xliv In 
a similar manner, the RADIANCE two-cohort design will potentially allow future development 
and eventual regulatory approval of Paradise System renal denervation in combination with 
multiple drug combinations/and or doses. 
 Justification for Efficacy Performance Criteria 
Incremental reductions in BP are known to decrease the incidence of major cardiovascular 
events. Reducing systolic BP by as little as 5 mmHg has been shown to be associated with a 
14% reduction in the incidence of stroke, a 9% reduction in the incidence of cardiovascular 
disease and a 7% reduction in mortality.xlv Furthermore, precedence from pharmaceutical 
evaluations of antihypertensive medicationxlviand from the recently presented DENERHTNxxxii, 
Symplicity Flexxlvii and Symplicity Japanxlviii trials support that a 6 mmHg reduction in BP 
between treatment and placebo or sham, is an achievable and clinically meaningful goal in both 
drug washout patients
 and in severely resistant and mildly resistant hypertensive patients.  

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  Minimization of Risk 
Since RADIANCE-HTN is the first randomized, blinded and controlled trial of the Paradise 
ultrasound technology, the following specific measures have been taken to ensure that subjects 
are not inappropriately exposed to an increased risk of cardiovascular events including stroke 
and/or renal stenosis: 
• Drug discontinuation in the RADIANCE Solo cohort will occur in line with accepted 
Institutional guidelines for a subjects’ current medication and subjects whose baseline 
eligibility systolic/diastolic office BP is ≥180/110 mmHg or baseline daytime ABP is 
≥170/105 mmHg are excluded   
• Drug discontinuation in the RADIANCE Solo cohort is limited to a short period of 
approximately 3 months during which timeframe subjects are a low risk of any CV 
event off treatmentxxxix 
• All subjects will be provided with home BP monitoring devices from the point of a) 
drug discontinuation or run-in (RADIANCE Solo cohort) or b) initiation of fixed dose 
triple combination therapy (RADIANCE Trio cohort)  
• Subjects whose average home BP increases to ≥170 systolic or ≥105 mmHg diastolic 
and who have clinical events considered to be related to persistent or elevated 
hypertension pre-randomization such that a change in medication is necessitated, will 
be excluded 
• Subjects whose average home BP increases to ≥170 systolic or ≥105 mmHg diastolic 
at any time post randomization will be eligible to have their antihypertensive 
medication restarted or modified as needed  
• Subjects in the RADIANCE Solo cohort will have antihypertensive drug therapy 
initiated immediately following the 2 month FU if needed 
• Non-invasive imaging will be required for all subjects at baseline (CTA/MRA at a 
minimum), the 2 and 6 month FUs (duplex ultrasound) and for all treated subjects at the 
12 month FU (CTA/MRA) and the 24 and 36 month FUs (duplex ultrasound)   
7. Subject Selection  
 
Study Population and Eligibility 
Subjects eligible* for antihypertensive drug therapy and following the general 
indications/contraindications for use of the Paradise Renal Denervation System will be 
identified from the general subject population by the enrolling center. In addition, subjects must 
meet all inclusion criteria and none of the exclusion criteria.  
 
*According to National or Institutional guidelines e.g. “Clinical management of primary hypertension 
in adults”, NICE Hypertension Guidelines, August 2011 
 
Inclusion Criteria 
Male and female subjects who meet all of the following criteria may be given consideration for 
inclusion in this clinical investigation, provided no exclusion criterion is met.  Minor 
differences in inclusion criteria exist for the RADIANCE Solo cohort versus the RADIANCE 
Trio cohort reflecting the different stage in hypertension progression of each group: 

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 Inclusion Criteria - RADIANCE Solo  
Subjects who meet any one of the following criteria should be given consideration for inclusion 
in the Solo Cohort: 
• Appropriately signed and dated informed consent  
• Age ≥18 and ≤75 years at time of consent 
• Documented history of essential hypertension  
• Either,  
o average seated office BP <180/110 mmHg at screening visit (V0) while on a 
stable regimen of 1 or 2 antihypertensive medications for at least 4 weeks prior 
to consent or,  
o Average seated office BP ≥ 140/90 mmHg <180/110 mmHg despite lifestyle 
measures on no antihypertensive medications 
• Documented daytime ABP ≥135/85 mmHg and <170/105 mmHg after 4-week 
washout/run-in period  
• Suitable renal anatomy compatible with the renal denervation procedure and documented 
by renal CTA or MRA of good quality performed within one year prior to consent (a CTA 
or MRA will be obtained in patients without a recent (≤1 year) renal imaging) 
• Able and willing to comply with all study procedures  
 Exclusion Criteria - RADIANCE Solo Cohort 
Subjects who meet any one of the following criteria will be excluded from the Solo Cohort: 
• Renal artery anatomy on either side, ineligible for treatment including: 
o Main renal artery diameter < 4 mm and > 8 mm 
o Main renal artery length < 25 mm 
o A single functioning kidney 
o Presence of abnormal kidney (or secreting adrenal) tumors  
o Renal artery with aneurysm 
o Pre-existing renal stent or history of renal artery angioplasty 
o Prior renal denervation procedure 
o Fibromuscular disease of the renal arteries 
o Presence of renal artery stenosis of any origin ≥ 30% 
o Accessory arteries with diameter ≥2mm <4 mm and > 8 mm* 
• Iliac/femoral artery stenosis precluding insertion of the Paradise Catheter 
• Evidence of active infection within 7 days of procedure 
• Type I diabetes mellitus or uncontrolled Type II diabetes (defined as a plasma Hb1Ac ≥ 
9.0%) 
• Documented history of chronic active active inflammatory bowel disorders such as Crohn’s 
disease or ulcerative colitis 
• eGFR of <40 mL/min/1.73 m2 (by Modification of Diet in Renal Disease formula) 
• Brachial circumference ≥ 42 cm 
• Any history of cerebrovascular event (e.g. stroke, transient ischemic event, cerebrovascular 
accident) 
• Any history of severe cardiovascular event (myocardial infarction, CABG, acute heart 
failure requiring hospitalization (NYHA III-IV) 
• Documented confirmed episode(s) of stable or unstable angina  
• Documented repeat (>1) hospitalization for hypertensive crisis within the prior 12 months 

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• Prescribed to any standard antihypertensive of cardiovascular medication (e.g. beta 
blockers) for other chronic conditions (e.g. ischemic heart disease) such that discontinuation 
might pose serious risk to health  
• Documented history of persistent or permanent atrial tachyarrhythmia 
• Active implantable medical device (e.g. ICD or CRT-D; neuromodulator/spinal stimulator; 
baroreflex stimulator) 
• Chronic oxygen support or mechanical ventilation other than nocturnal respiratory support 
for sleep apnea. 
• Primary pulmonary hypertension 
• Documented contraindication or allergy to contrast medium not amenable to treatment 
• Limited life expectancy of < 1 year at the discretion of the Investigator 
• Any known, unresolved history of drug use or alcohol dependency, lacks the ability to 
comprehend or follow instructions, or for any reason in the opinion of the investigator, 
would be unlikely or unable to comply with study protocol requirements or whose 
participation may result in data analysis confounders (e.g. night shift workers) 
• Pregnant, nursing or planning to become pregnant (documented negative pregnancy test 
required documented within a maximum of 7 days prior to procedure for all women of child 
bearing potential. Documentation of effective contraception is also required for women of 
child bearing potential)  
• Concurrent enrollment in any other investigational drug or device trial (participation in non-
interventional Registries is acceptable) 
* This exclusion criteria may only be finally determined during the active renal angiogram procedure, 
subjects will therefore only count towards the enrollment ceiling at the time of randomization 
 Inclusion Criteria - RADIANCE Trio Cohort 
Subjects who meet any one of the following criteria should be given consideration for inclusion 
in the Trio Cohort: 
• Appropriately signed and dated informed consent 
• Age ≥18 and ≤75 years at time of consent 
• Documented history of hypertension  
• Average seated office BP ≥140/90 mmHg at screening visit (V0) while on a stable regimen 
of at least 3 antihypertensive medications of different classes including a diuretic for at least 
4 weeks prior to consent 
• Documented daytime ABP ≥ 135/85 mmHg after 4-week stabilization period  
• Suitable renal anatomy compatible with the renal denervation procedure and documented 
by renal CTA or MRA of good quality performed within one year prior to consent (a CTA 
or MRA will be obtained in patients without a recent (≤1 year) renal imaging)  
• Able and willing to comply with all study procedures  
 Exclusion Criteria - RADIANCE Trio Cohort 
Subjects who meet any one of the following criteria will be excluded from the Trio Cohort. 
• Renal artery anatomy on either side, ineligible for treatment including: 
o Main renal artery diameter < 3 mm or > 8 mm 
o Main renal treatable artery length < 20 mm (may include proximal branching) 
o A single functioning kidney 
o Presence of abnormal kidney tumors   
o Renal artery with aneurysm 

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o Pre-existing renal stent or history of renal artery angioplasty 
o Pre-existing aortic stent or history of aortic aneurysm 
o Prior renal denervation procedure 
o Fibromuscular disease of the renal arteries 
o Presence of renal artery stenosis of any origin ≥ 30% 
o Accessory arteries with diameter ≥2mm <3 mm or > 8 mm* 
• Iliac/femoral artery stenosis precluding insertion of the Paradise Catheter 
• Evidence of active infection within 7 days of procedure 
• Secondary hypertension not including sleep apnea (documented through clinical work up 
within the 12 months prior to consent- see Section 7.2.4.1) 
• Type I diabetes mellitus or uncontrolled Type II diabetes (defined as a plasma Hb1Ac ≥ 
9.0%) 
• Documented history of chronic active inflammatory bowel disorders such as Crohn’s 
disease or ulcerative colitis 
• eGFR of <40 mL/min/1.73 m2 (by Modification of Diet in Renal Disease formula) 
• Brachial circumference ≥ 42 cm 
• Any history of cerebrovascular event (e.g. stroke, transient ischemic event, cerebrovascular 
accident) within 3 months prior to consent 
• Any history of severe cardiovascular event (myocardial infarction, CABG, acute heart 
failure requiring hospitalization (NYHA III-IV) within 3 months prior to consent 
• Documented confirmed episode(s) of unstable angina within 3 months prior to consent 
• Documented intolerance or contraindication for any of the antihypertensive drugs 
prescribed as a requirement of the study protocol  
• Documented repeat (>1) hospitalization for hypertensive crisis within the prior 3 months 
• Prescribed to any standard anti-hypertensive CV medication (other than beta blockers) for 
other chronic conditions (e.g. ischemic heart disease) such that discontinuation might pose 
serious risk to health  
• Documented history of persistent or permanent atrial tachyarrhythmia 
• Active implantable medical device (e.g. ICD or CRT-D; neuromodulator/spinal stimulator; 
baroreflex stimulator) 
• Chronic oxygen support or mechanical ventilation other than nocturnal respiratory support 
for sleep apnea. 
• Primary pulmonary hypertension 
• Documented contraindication or allergy to contrast medium not amenable to treatment 
• Limited life expectancy of < 1 year at the discretion of the Investigator 
• Night shift workers 
• Any known, unresolved history of drug use or alcohol dependency, lacks the ability to 
comprehend or follow instructions, or for any reason in the opinion of the investigator, 
would be unlikely or unable to comply with study protocol requirements or whose 
participation may result in data analysis confounders 
• Pregnant, nursing or planning to become pregnant (documented negative pregnancy test 
required documented within a maximum of 7 days prior to procedure for all women of child 
bearing potential. Documentation of effective contraception is also required for women of 
child bearing potential)  
• 
Concurrent enrollment in any other investigational drug or device trial (participation in non-
interventional Registries is acceptable) 
 
* This exclusion criteria may only be finally determined during the active renal angiogram procedure, subjects 
will therefore only count towards the enrollment ceiling at the time of randomization 
 

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7.2.4.1. Secondary Hypertension 
It is important to ensure that in treatment resistant hypertensive subjects, potential secondary 
causes of hypertension are ruled out. It is expected that evidence of clinical work up to exclude 
the most commonly diagnosed secondary forms of hypertension will have been documented 
within the 12 months prior to subject consent. Study-required tests can also be used to diagnose 
causes of secondary hypertension as needed (e.g. baseline blood and urine chemistry 
CTA/MRA).  Secondary forms of hypertension are shown in Table 7.2-1 (adapted from the 
Seventh report of the Joint National Committee on prevention, detection, evaluation and 
treatment of high blood pressureii and ESH/ESC 2013), as well as instances in which it would 
be expected that additional testing would be required in the absence of existing documentation.  
Subjects with sleep apnea are NOT excluded. 
 
Table 7.2-1: Secondary Hypertension Screening 
  
 
Condition 
Screening test 
Comment 
Primary Aldosteronism 
Plasma aldosterone/renin 
ratio/24-hour urinary 
aldosterone.  Adrenal CT if 
needed 
Documentation of exclusion in TRIO 
cohort will be required (acceptable 
within 1 year of consent) but can be 
excluded via the study-defined 
imaging (CTA/MRA) by 
visualization of the adrenal glands  
Renovascular 
Hypertension 
CT angiography; MR 
Angiography; renal angiogram 
Documentation of exclusion in TRIO 
cohort will be required (acceptable 
within 1 year of consent) but can be 
excluded via study-defined imaging 
(CTA/MRA) and renal angiogram if 
required 
Pheochromocytoma 
History/ 24-hour urinary or 
plasma metanephrine and 
normetanephrine 
Presence of secreting adrenal tumors 
is already an exclusion criteria for 
both the SOLO and the TRIO cohort. 
Can be excluded via study-defined 
imaging including CTA and MRA  if 
required 
Chronic Kidney Disease 
Estimated glomerular filtration 
rate (eGFR); spot urine test for 
albumin/creatinine ratio, 
An eGFR of <40 mL/min/1.73 m2 is 
an exclusion criteria for both the 
SOLO and the TRIO cohort. 
Hypothyroidism/ 
Hyperthyroidism 
Thyroid Stimulating Hormone 
tests (TSH) 
Thyroxine/Triiodothyronine 
Documentation of testing only 
required in the event of clinical 
suspicion physical/history etc   
Cushing Syndrome 
History/physical 
Rare. Documentation of testing only 
required in the event of clinical 
suspicion physical/history etc   
Coarctation of the Aorta 
CTA or MRA imaging 
Rare. Documentation of testing only 
required in the event of clinical 
suspicion based on physical/history 
etc   
Hyperparathyroidism 
Hypercalcemia 
Rare. Documentation of testing only 
required in the event of clinical 
suspicion physical/history etc   

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8. Subject Accountability 
 
Point of Enrollment 
All subjects will be considered enrolled following the signing of an informed consent. Since 
full eligibility for the study may not be confirmable without ABP results after 4-weeks and the 
need for an invasive procedure (it is possible that the renal anatomy eligibility criteria and full 
exclusion of secondary hypertension may only be confirmed during the active renal angiogram 
procedure) enrolled subjects will only count towards the enrollment ceiling at the time of 
randomization.   
 
Re-Consent 
Under specific circumstances, a subject that has previously been found to be ineligible for the 
study during screening (“Screening Failures – see Section 8.4) may be re-consented (e.g. 
reduced brachial circumference due to weight loss; clinically driven changes in anti-
hypertensive medication resulting in a change in eligibility; changes to diabetes management 
etc.).  Any subject that is being considered for re-consent will be approved by the Sponsor. 
 
Withdrawal 
All subjects included in the RADIANCE study (including those who have withdrawn or been 
lost to FU) shall be accounted for and documented. If a subject withdraws from the clinical 
investigation, the reason(s) shall be reported. If such withdrawal is due to an adverse event, the 
subject will be followed until resolution of that adverse event or it is otherwise deemed that the 
event can be closed (e.g. a chronic event), whichever is most applicable to the situation. 
Limiting the amount of missing data is key to the successful outcome of the study however, 
subjects may withdraw from the study at any time with, or without reason. Withdrawal will in 
no way prejudice the subject’s access to further treatment. Attempts to contact subjects who are 
lost to FU will be documented (e.g. phone calls; email; letter). Additional data may not be 
collected after the point at which a subject has withdrawn from the study. Reasons for 
withdrawal include but are not limited to: 
• Physician discretion 
• Subject choice (withdrawal of consent) 
• Lost to FU  
• Death 
Return of home BP monitoring systems after withdrawal for reasons of physician or subject 
preference is recommended. Withdrawal from the study will be documented on the Study Status 
form 
 
Subject Status and Classification  
The following classifications will be applied to all subjects: 
 
• Screening Failure: A subject who has signed the informed consent but is found to not meet 
eligibility criteria either through medical file review or other study-dependent procedures 
other than the renal angiogram. The original Consent form and screening documentation for 
these subjects should be maintained in the Center’s files. There are no FU requirements for 
Screening Failures unless in the event of an adverse event that occurred during the process 

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of defining eligibility, in which case the status of the event will be reviewed and documented 
within 30 days. Home BP devices will be returned to the investigational center.   
• Attempt: A subject who signs the informed consent, meets eligibility criteria and has any 
form of anesthesia/analgesia administered for the procedure but was not successfully treated 
per the protocol.  This includes subjects excluded by renal angiogram. All attempt subjects 
will be followed for 30 days post procedure for safety and any adverse events that occur 
within that period will be collected. Follow-up can be conducted by phone, email, office 
visit.   Home BP monitors should be returned to the investigational center for these subjects. 
Exit from the study will be documented on the Study Status form. 
• Treatment: A subject who is successfully randomized per the study protocol. These subjects 
are followed in accordance with the FU schedule. Any subject that has been randomized, 
will count towards the enrollment ceiling even in the event that the treatment was not 
completed per protocol. These subjects will be provided with a Home BP Monitor for the 
duration of the study. 
The pre-specified statistical analysis will be documented in the Statistical Analysis Plan. 
9. Methods 
 
Visit schedule 
Enrollment of subjects will occur at the clinical sites only after the appropriate Local and 
National study approvals, “Approval to Enroll” documentation from the Sponsor and written 
informed consent from subjects have been obtained. Table 9.1-1 summarizes the study visit 
schedule (see text for details): 

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Table 9.1-1: Visit Schedule 
Visit 
V0 
V1 
NA 
P1 
D1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
Visit Description 
Screening   
Baseline 
Eligibility  
Pre-
Procedure 
 Testing  
Procedure 
Discharge 
1 Mo  
FU 
2 Mo  
FU 
3 Mo  
FU 
4 Mo  
FU 
5 Mo  
FU 
6 Mo  
FU 
12 Mo 
FU 
24 Mo 
FU 
36 Mo 
FU 
48 Mo 
FU 
60 Mo 
FU 
Visit Window (days) 
NA 
28±3  
post V0 
 
Max 21 days 
post V1 
NA 
30±7  
60±7  
90±7 
120±7 
150±7 
180±7 
360±14 
720±30 
1080±30 
1440±60 
1880±60 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Average Office BP* 
X 
X 
 
 
X+ 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
24-hour Ambulatory BP 
 
X 
 
 
 
 
X 
 
 
 
X 
X 
 
 
 
 
Home BP Review € 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Medical history (or review) 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Examination 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medication Review  
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
HTN Medication Withdrawal 
(Solo Cohort) 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
Triple HTN Therapy  
 (Trio Cohort) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X∞ 
 
 
 
 
 
HTN Therapy Escalation           
(if needed per BP criteria) 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
12-lead ECG 
 
X 
X≠ 
 
 
 
X 
 
 
 
X 
X 
 
 
 
 
Renal Duplex Ultrasound 
 
 
X¥ 
 
 
X$ 
X 
X$ 
X$ 
X$ 
X 
X$ 
XT 
XT 
 
 
CTA/MRA 
 
 
X** 
 
 
 
X$ 
 
 
 
X$ 
XT 
 
 
 
 
Urine Chemistry 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
 
 
 
Urine for Drug Metabolite (Trio 
Cohort Only) 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
 
 
Blood Chemistry 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
 
 
 
Plasma for Biomarkers         
(Solo Cohort Only - optional) 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
 
 
 
Pregnancy Test (where applicable) 
 
 
X# 
 
 
 
 
 
 
 
 
 
 
 
 
 
Diagnostic renal angiogram 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Renal Denervation Procedure 
 
 
 
XT 
 
 
 
 
 
 
 
 
 
 
 
 
Pain Perception Evaluation 
(Visual Analog Scale) 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Blinding Index 
 
 
 
 
X 
 
X 
 
 
 
X 
 
 
 
 
 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Device Deficiencies 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol Deviations 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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BP: Blood Pressure; HTN: hypertension; CTA: Computed Tomographic Angiography; MRA; Magnetic Resonance Angiogram; 
* Average seated Office BP will be from an average of a minimum of 3 seated measurements as well as standing measure unless specified (See Section 10.1) 
+ Measurement of Standing Office BP is optional at Discharge Visit 
∞ Triple HTN therapy is continued up to the 6-month visit. Following completion of the 6-month visit, antihypertensive medication is per physician discretion  
≠ If not done at Baseline Visit V1 
¥ Recommended. A recent (within 6 months of consent) good quality renal duplex ultrasound is acceptable 
# within a maximum of 7 days prior to procedure 
$ if required in the event of clinical suspicion of renal artery stenosis 
** A recent (within 12 months of consent) good quality, renal MRA or CTA is acceptable 
XT Treated Subjects 
€ Home BP readings start 7 days prior to scheduled office visit 
Note: Pre-procedure tests may be completed at any time from the point a subject attends the Screening Visit (V0) up to the Procedure. Review of CTA/MRA images by the 
Sponsor in collaboration with the clinical site is required prior to procedure. Allow sufficient time for scheduling if required. 
 
 

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Table 9.1-2: Visit Schedule for Cross-over Patients 
Visit 
COV1 
COP2 
COD2 
COV2 
COV3 
COV4 
COV5 
COV6 
COV7 
COV8 
COV9 
Visit Description 
Cross-over 
Baseline 
Evaluation 
Cross-over 
Procedure 
Cross-over 
Discharge 
Cross-over 
1 Mo  
FU 
Cross-over 
2 Mo  
FU 
Cross-over 
6 Mo  
FU 
Cross-over 12 
Mo 
FU 
Cross-over 
24 Mo  
FU 
Cross-over 
36 Mo  
FU 
Cross-over 
48 Mo  
FU 
Cross-over 
60 Mo  
FU 
Visit Window (days) 
NA 
Max 21 days post 
COV1 
NA 
30±7  
post COP2 
60±7  
post COP2 
180±7 
post COP2 
360±14 
post COP2 
720±30 
post COP2 
1080±60 
post COP2 
1440±60 
post COP2 
1880±60 
post COP2 
Cross over consent 
X 
 
 
 
 
 
 
 
 
 
 
Cross-over eligibility evaluation 
X 
 
 
 
 
 
 
 
 
 
 
Average Office BP* 
X 
 
X+ 
X 
X 
X 
X 
X 
X 
X 
X 
24-hour Ambulatory BP 
X£ 
 
 
 
X 
X 
X 
 
 
 
 
Medical history review 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Examination 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Medication Review  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CTA/MRA 
 
 
 
 
 
 
X 
 
 
 
 
Renal Duplex Ultrasound 
 
 
 
 
X 
X 
 
X 
X 
 
 
Blood Chemistry 
X£ 
 
 
 
X 
X 
X 
 
 
 
 
Urine Chemistry 
X£ 
 
 
 
X 
X 
X 
 
 
 
 
Pregnancy Test (where applicable) 
X# 
 
 
 
 
 
 
 
 
 
 
Diagnostic renal angiogram 
 
X 
 
 
 
 
 
 
 
 
 
Renal Denervation Procedure 
 
X 
 
 
 
 
 
 
 
 
 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Device Deficiencies 
 
X 
 
 
 
 
 
 
 
 
 
Protocol Deviations 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
BP: Blood Pressure; HTN: hypertension; CTA: Computed Tomographic Angiography; MRA; Magnetic Resonance Angiogram; 
*Average seated Office BP will be from an average of a minimum of 3 seated measurements as well as standing measure unless specified (See Section 10.1) 
+ Optional 
# within a maximum of 7 days prior to procedure 
£ Results from tests recently performed during study follow-up visits may be used unless there were major changes to the patient condition or treatment.  
 
 

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V0: Study Screening Visit 
Subjects who meet general eligibility for consideration for the study will sign an informed 
consent and be assigned to one of the two study cohorts. All subjects will have their seated 
average office BP measured (see Section 10.1), a limited medical history review, physical exam 
and current medication review.   
 RADIANCE Solo Cohort 
Subjects eligible for the RADIANCE Solo Cohort currently prescribed to hypertensive BP 
medication with systolic office BP < 180 mmHg, will be asked to stop taking all hypertensive 
medication for the 4 week wash-out period (follow Institutional guidelines for wash-out of 
current hypertension medication). Subjects assigned to the RADIANCE Solo Cohort currently 
not prescribed to hypertensive BP medication with office BP ≥ 140/90 mmHg < 180/110 
mmHg, will be asked to stay medication-free for a 4-week run-in period.  
 RADIANCE Trio Cohort 
Subjects eligible for the RADIANCE Trio cohort will be asked to stop their current 
hypertensive medication and replace it with the study-defined medication regimen (see Section 
9.12.2) for the 4-week stabilization period.  
All subjects will be provided with a home BP monitoring system, trained on its use and asked 
to take their home BP (see Section 10.3) for 7 consecutive days prior to the return visit to the 
investigational site (Baseline Eligibility Visit). They will also be given a patient diary.  
 
Table 9.2-1: Data to be collected during the screening visit (V0) 
Data Collection 
Location of Source 
Average office BP Measurement per guidelines (including 
standing BP) 
Maintain at site 
Limited medical history and physical examination including but 
not limited to gender, age at consent, height, weight, relevant 
cardiovascular history 
Maintain at site 
Renal CTA/MRA Review (if available) 
Upload copy  
Renal duplex ultrasound review (if available) 
Upload copy  
Current medication (hypertensive and non-hypertensive) 
Maintain at site 
 
V1: Baseline Eligibility Visit  
All subjects will return to the clinical center to have their office BP measured 4 weeks (±3 days) 
after either the discontinuation of their hypertensive medication (or the run-in period for those 
subjects without prescribed antihypertensive therapy) or the replacement of their current 
hypertensive medication with the study-defined medication regimen.  
 
It is strongly recommended that the V1 visit occur between 08:00 and 10:00am following an 8-
hour overnight fast. RADIANCE Trio subjects will be asked to not take their morning dose of 
antihypertensive medication but instead to bring their medication with them to the V1 visit. The 
investigational center may contact the study subject 24-hrs prior to V1 to remind them of the 
need for overnight fasting and for RADIANCE Trio subjects, to bring their morning 
hypertensive medication to the FU. 

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All subjects will have a seated office BP measurement recorded (see Section 10.1) and will 
undergo ABP measurement following training on how to use the ABP device. Once the device 
is started, RADIANCE Trio subjects will receive the morning dose of their antihypertensive 
treatment.  Subjects will be requested to return the ABP device within approximately 24 hours. 
Since this ABP data marks the point of eligibility for the study, it is strongly recommended that 
subjects return to the clinical center with the ABP device.  
 
Table 9.3-1: Data to be collected during the Baseline Eligibility Visit (V1) 
Data Collection 
Location of Source 
Average office BP Measurement per guidelines 
(including standing BP) 
Maintain at site 
Home BP measurements and review of diary entries 
Maintain copy at site 
Physical examination  
Maintain at site 
Current medication (hypertensive and non-hypertensive) 
Maintain at site 
Documentation of any adverse events 
Original at site. Upload copy to 
database as requested (SAE; SADE) 
Protocol Deviations 
Maintain at site 
 
 Baseline ABP Review and Final Eligibility Testing 
Subjects in the RADIANCE Solo cohort whose baseline, daytime ABP is documented to be 
≥135/85 mmHg and <170/105 mmHg* and subjects in the RADIANCE Trio cohort whose 
daytime ABP is documented to be ≥135/85 mmHg, will be considered eligible for the study and 
asked to complete final pre-procedure eligibility tests (See section 9.3.2).   
 
*Note: in the event of a technical failure or if insufficient or inadequate data is available following the 
24-hr ABP recording to determine eligibility, the subject may be asked to repeat the measurement  
 
Table 9.3-2: Data to be collected during ABP Review 
Data Collection 
Location of Source 
24-hour ABP report 
Upload to core lab. Maintain copy of report at site 
Documentation of any adverse events 
Original at site. Upload copy to database (SAE; 
SADE) 
Protocol Deviations 
Maintain at site 
 
Table 9.3-3: Data to be collected following eligibility by ABP 
Data Collection 
Location of Source 
Review and update of medication history 
Maintain at site 
 
 
Subjects who do not meet the protocol-defined ABP criteria will not be deemed eligible to 
continue in the study and will be withdrawn from the study and classified as “Screening 
Failures” (See section8.4).  These subjects may then return to standard of care and home BP 
monitoring systems should be returned to the clinical center.  
 Additional Pre-Procedure Testing 
Once the ABP eligibility has been confirmed, there are a number of additional tests that are 
required to be completed prior to the Procedure. These tests may be completed pre-emptively 

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as part of the V1 visit or completed during the visit when the subject returns to the hospital with 
their ABP device or may be scheduled separately at any time post V0.  
 
Table 9.3-4: Testing to be completed prior to Procedure  
Data Collection 
Location of Source 
Screening renal CTA or MRA to evaluate renal anatomy (a recent 
CTA or MRA within 12 months of consent is acceptable). Requires 
review by Sponsor prior to Procedure  
Upload copy  
Screening renal duplex ultrasound (optional) 
Upload copy  
Baseline 12-lead ECG 
Maintain at site  
Baseline urine (for chemistry both cohort and drug screening – Trio 
Cohort Only) 
Maintain at site 
Baseline Blood (for chemistry)  
Maintain at site 
Baseline Blood (plasma for biomarkers- Solo Cohort Only- optional 
test) 
Maintain at site 
Negative Pregnancy test (within 7 days of procedure if applicable) 
Maintain at site 
 
The screening CTA/MRA will need to be evaluated by at a minimum, a designated Sponsor 
representative in collaboration with the clinical site. For this reason, the CTA/MRA should be 
scheduled to allow sufficient time for review. In the event the screening CTA or MRA 
documents an ineligible renal anatomy or evidence for any other exclusion criteria, the subject 
will not be eligible for the procedure and will be classified as an “Screening Failure” (see 
section 8.4). These subjects will be withdrawn from the study and may return to standard of 
care.  Home BP systems should be returned to the clinical center.   A baseline renal duplex 
ultrasound is also strongly recommended. 
 
P1. Hospitalization for Renal Denervation or Blinded (Sham) Procedure 
Once a subject has met all the screening criteria for the study including diagnostic CTA or 
MRA, they will be scheduled for the renal angiogram and renal denervation procedure. The 
procedure may not occur later than a maximum of 21 days after the V1 visit.  In the event a 
procedure cannot be scheduled within that time frame the Sponsor must be notified.  Subjects 
of child bearing potential must have a documented negative pregnancy test dated within a 
maximum of 7 days prior to the procedure. 
 Blinding Process 
No study personnel who will be responsible for recording patient BP during FU may be present 
at the point of randomization which occurs after the completion of the diagnostic renal 
angiogram.  All patients will be sedated prior to randomization. In addition the use of 
headphones and eye covers is required for any subjects that are not under general anesthesia.  
Other methods of blinding such as standardization of length of time spent in the cath lab for 
blinded controls, removal of clocks in recovery room and prevention of contact between 
subjects treated on the same day may be considered and will be collected if used.   
 Hypertensive Medications Pre-Procedure 
Any changes in antihypertensive medication since the V1 visit will be documented. This does 
not include any transient changes that occur specifically for the procedure. The use of temporary 
pharmacologic intervention for control of blood pressure prior to and during the peri-procedural 

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phase in order to minimize the risks of puncture site hematoma, is permissible per physician 
discretion.  
 Procedural Medications 
Appropriate systemic anti-coagulation shall be administered prior and/or during treatment to 
minimize the risk of thrombus formation.  The risks of using the Paradise System in patients 
who cannot be anti-coagulated are unknown.  The same anticoagulation procedures should be 
observed for all patients. The clinician can consider the use of low dose prophylactic aspirin if 
recommended by local clinical practice.  
Understanding that there is evidence that the renal denervation treatment may be associated 
with pain, appropriate analgesic/anxiolytic medication to ensure subject comfort and to 
maintain blinding is required. Medications such as Morphine sulphate, Fentanyl and Midazolam 
are recommended and should be administered as per local policy. The use of intra-arterial 
vasodilators for prevention or treatment of renal artery spasm is per physician discretion.   It is 
recognized that this procedure may require a deeper level of sedation than for standard 
percutaneous procedures.   Accordingly, investigators should ensure that appropriate post-
procedural monitoring is in place for subjects, particularly taking into account that the 
population may be elderly and hypertensive.  Monitoring should be per institutional guidelines.    
 Diagnostic Renal Angiogram (all subjects) 
All subjects will undergo a diagnostic, renal angiogram which should be per Institutional 
practice via femoral artery access. The Paradise System requires the use of a 7 French guide 
catheter (minimum diameter; see Section 4.3.2).  It is recommended, however, that investigators 
use a smaller size access sheath (e.g. 4 or 5 French) to perform the diagnostic angiogram consistent 
with standard institutional practice; and that for those patients randomized to renal denervation, the 
sheath be exchanged for a larger one to accommodate the Paradise System.  
 
Treatment is required to be bilateral therefore angiographic evidence of any of the following 
criteria on either side, would deem the subject as ineligible for randomization: 
• Main renal artery diameter < 3 mm > 8mm 
• Main renal treatable length < 20mm 
o A minimum of 20mm treatable length will allow for delivery of at least two 
emissions in each renal artery.  Treatable length may include artery branches  
(artery length is best determined by CTA/MRA)  
• A single functioning kidney 
• Abnormal kidney or secreting adrenal tumor  
• Renal artery with aneurysm  
• Pre-existing renal stent 
• Pre-existing aortic stent  
• Prior renal denervation procedure 
• Fibromuscular disease of the renal arteries 
• Presence of renal artery stenosis of any origin ≥ 30% 
• Accessory arteries with diameter ≥2mm<3 mm or >8mm 
 
In the event that all these angiographic criteria cannot be confirmed with a global angiogram, 
a selective renal angiogram may be conducted.  

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 Randomization 
Randomization will occur following the diagnostic renal angiogram. Only randomized 
patients will count towards the enrollment ceiling. 
 Blinded (Sham) Procedure 
For the blinded control patients, the diagnostic renal angiogram will be considered the sham 
procedure. 
 Renal Denervation Procedure 
Specific details of the renal denervation procedure will be provided in the Manual Operations. 
Briefly, using standard interventional technique, gain access to the femoral artery and place a 
guide catheter compatible with the Paradise System (0.081” minimum inner diameter; 7 
French). Carefully advance the guide catheter into the left or right renal artery using 
fluoroscopic guidance.  Verify patency by performing an angiogram and measure the distal. 
mid and proximal artery diameters in order to select the appropriate Paradise catheter balloon 
size (see Table 9.4-1). Select the Paradise Catheter based on the smallest measured diameter of 
the artery and follow these steps to deliver treatment bilaterally: 
 
Table 9.4-1: Paradise Catheter Range 
 
Artery Diameter 
Range 
Catheter Reference 
Balloon diameter 
3 to <3.5mm 
PRDS-063-02 
3.5 mm 
3.5 to <4.2mm 
PRDS-064-02 
4.2 mm 
4.2 to <5 mm 
PRDS-065-02 
5 mm 
5 to <6 mm 
PRDS-066-02 
6 mm 
6 to <7 mm 
PRDS-067-02 
7 mm 
7 to ≤8 mm 
PRDS-068-02 
8 mm 
 
• Prepare and attach the Paradise Cartridge, Paradise Connection Cable, and sterile water supply 
as per the  Instructions for Use  
• Using sterile technique, open the Paradise Catheter package and carefully remove the device.   
• Connect the Paradise Cartridge extension tubing to the fluid luer connections of the Paradise 
Catheter.  The order of connections does not matter 
• Prepare the Paradise Catheter according to the Instructions for Use 
• Flush the center lumen of the Paradise Catheter prior to tracking over a wire 
• Remove access devices from lumen of guide catheter and insert a 0.014” guidewire 
• Verify the balloon on the Paradise Catheter is deflated. If balloon is not deflated, press the 
DEFLATE button on the Paradise Generator touch screen to deflate the balloon 
• Track the Paradise Catheter over the 0.014” guidewire and gently insert the Paradise Catheter 
into the “Bleedback” hemostasis valve and guide catheter 
• Advance the Paradise Catheter into the renal artery 
• See the Instructions for Use for balloon inflation, sonication, and balloon deflation instructions 
• Treatment Strategy 
o Deliver a minimum of two sonications each in the left and right renal arteries 
(see Figure 8.4-1 for an example treatment strategy).   

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▪ The first sonication should be delivered at a distance of at least 5 mm, or one (1) 
radiopaque transducer length, from the artery bifurcation   
▪ Additional sonications should be delivered in a non-overlapping configuration, 
with each subsequent sonication delivered proximal to the prior sonication.  
Note: Do not place sonication over the ostium of a branch vessel 
▪ If proximal artery branching, and diameter of branch is ≥ 3 mm, one (1) 
sonication should be delivered in the branch in a location at least 5 mm from the 
kidney parenchyma, and at least 10mm from adjacent sonicationsIf proximal 
bifurcating branches (>3 mm diameter) in short main renal arteries, a 
minimum of one (1) sonication should be delivered in each branch in a location 
at least 5 mm from the kidney parenchyma, and at least 10 mm from adjacent 
sonications 
▪ Maintain a gap of ≥ 5 mm, or at least one (1) radiopaque transducer length 
between the final sonication and the renal artery/aorta ostium 
o If an accessory artery/side branch is present and has a diameter ≥ 3 mm, one (1) 
sonication should be delivered  
• When treatment in either the left or right artery is completed, withdraw the Paradise 
Catheter back into the guide catheter 
• Position the guidewire and guiding catheter into the non-treated artery and repeat procedure 
• Remove the Paradise Catheter, guidewire and guide catheter after treatment of both arteries. 
• Close the wound per standard Institutional practice taking into consideration the size of the guide 
catheter(s) used. Follow standard-of-care post-intervention monitoring procedures including 
pain control, post sedation monitoring and FU 
 
The Paradise catheter and accessories should be returned to the Sponsor. If the devices are not 
returned, appropriate disposal must be documented. 
 
Figure 9.4-1: Examples of Treatment Strategy in Renal Artery, Accessory Artery, and 
Proximal Side Branch 
 
9.4-1a:  Three ultrasound sonications in main renal artery 
 
 
 

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9.4-1b:  Two ultrasound sonications in main renal artery and one in proximal side branch 
artery 
 
 
9.4-1c: One ultrasound sonication in main renal artery and one in proximal bifurcating 
branches 
 
 
 
 
9.4-1d: Three ultrasound sonications in main renal artery and one in accessory renal artery 

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 Data Collection 
Table 9.4-2 documents the data to be collected during the renal denervation or blinded control 
(sham) procedure.  
 
Table 9.4-2: Data to be collected during the Procedure (P1) 
Data Collection 
Location of Source 
Visual Analog Pain Assessment (prior to procedure) 
Upload copy to database 
Procedure times (femoral access to femoral closure) 
Maintain at site 
Procedural Medication (temporary anti-hypertensive 
medication; anesthesia; analgesia; anticoagulation if used; 
contrast volume; radiation dose etc.) 
Maintain at site 
Renal anatomy detail from renal angiogram                   
(global or selective) 
Upload copy. Maintain copy of report 
at site 
Randomization 
CRF or equivalent 
Procedural angiogram 
Upload copy. Maintain copy at site 
unless requested 
Treated Subjects: Device and generator data including all 
accessories (guide catheters; guide wires) 
Maintain at site 
Treated Subjects: Paradise catheter usage; ultrasound 
ablation detail 
Maintain at site 
Adverse Events 
Original at site. Upload copy to 
database (SAE, SADE) 
Device Deficiencies 
Upload copy to database 
Protocol Deviations 
Maintain at site 
 Post Procedural Pain Assessment 
Subjects will be asked to complete a Visual Analog Pain Assessment (see Appendix A) prior 
to the procedure and again before they leave the hospital. 

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D1. Hospital Discharge  
Subjects will be discharged from the hospital according to institutional process. It is 
recommended that personnel un-blinded to the subjects’ randomization conduct the follow-up. 
Table 9.5-1 documents the data to be collected prior to discharge from the hospital. 
 
Table 9.5-1: Data to be collected prior to Discharge (D1) 
Data Collection 
Location of Source 
Average office BP Measurement per guidelines 
(measurement of standing office BP is optional) 
Maintain at site 
Visual Analog Pain Assessment 
Upload copy to database 
Blinding Index 
Maintain at site 
Adverse Events 
Original at site. Upload copy to database 
(SAE, SADE) 
Protocol Deviations 
Maintain at site 
 
Following discharge from the hospital, subjects will remain in their assigned cohort at least 
through the 2-month FU visit, with respect to remaining free of hypertensive medication 
(RADIANCE Solo Cohort) or compliant with the study-prescribed fixed drug regimen 
(RADIANCE Trio Cohort) unless in the event of a BP emergency or other clinical events that 
deem a change of medication may be necessary (see Section 9.12). 
 
In Clinic Follow-up Visits 
Subjects will be required to return to their investigational clinical center for FU 1, 2, 3, 4, 5, 6, 
12, 24, 36, 48 & 60 months post-procedure date.  Whenever possible, study assessments will 
be made by the same designated member of the study team. Home BP measurements will be 
collected for the 7 consecutive days prior to the office visit up to and including the 12-month 
FU (see Section 10.3). It is recommended that the investigational site contact the subject 
approximately 7 days prior to the office visit to remind them to begin their Home BP 
measurements.  
 
It is strongly recommended that all in-clinic visits be scheduled between 08:00 and 10:00am 
following an 8-hour overnight fast. Subjects taking study-defined antihypertensive medication 
at any time during the trial will be asked to not take their morning dose of antihypertensive 
medication but instead to bring their medication with them to the visit. The investigational 
center may contact the study subject 24-hrs prior to each visit to remind them of the need for 
overnight fasting and to bring their morning hypertensive medication to the FU (See Section 
9.12).  
 V2: One month Visit (30±7 days post procedure) 
Subjects will be required to return to their investigational clinical center one (1) month post 
procedure. Table 9.6-1 documents the data to be collected. 
Table 9.6-1: Testing to be collected at one month visit (V2) 
Data Collection 
Location of Source 
Average office BP Measurement per guidelines 
(including standing office BP) 
Maintain at site 
Home BP measurements and review of diary entries 
Maintain copy at site 
Physical examination  
Maintain at site 

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Changes in medication 
Maintain at site 
Adverse Events 
Original at site. Upload copy to 
database (SAE, SADE) 
Protocol Deviations 
Maintain at site 
 
 V3: Two Month Primary Efficacy Endpoint Visit (60±7 days post 
procedure) 
Subjects will be required to return to their investigational clinical center two (2) months post 
procedure. The two month visit marks the timing of the Primary Efficacy endpoint data 
collection but patients will remain blinded through to the 6-month FU visit. Changes in 
hypertension medication are permissible in both cohorts following the two month visit as 
described in Section 9.12.  Table 9.6-2 documents the data to be collected. 
Table 9.6-2: Testing to be collected at two month visit (V3) 
Data Collection 
Location of Source 
Average  office BP Measurement per guidelines 
(including standing office BP) 
Maintain at site 
24-hour ABP report* 
Upload to core lab. Maintain copy of 
report at site 
Home BP measurements and review of diary entries 
Maintain copy at site 
Urine (for chemistry – both cohort and drug screening 
– Trio Cohort Only) 
Maintain at site 
Blood (for chemistry) 
Maintain at site 
Blood (plasma for biomarkers- Solo Cohort only- 
Optional test)  
Maintain at site 
12-lead ECG 
Maintain at site 
Renal Duplex Ultrasound 
Upload copy. Maintain copy of report at 
site 
Physical examination  
Maintain at site 
Changes in medication 
Maintain at site 
Blinding Index 
Maintain at site 
Adverse Events 
Original at site. Upload copy to database 
(SAE, SADE) 
Protocol Deviations 
Maintain at site 
 
*Note: in the event insufficient data is available following the 24-hr ABP recording to determine 
eligibility, the subject will be asked to repeat the measurement 
 V4: Three Month Visit (90±7 days post procedure) 
Subjects will be required to return to their investigational clinical center three (3) months post 
procedure. Table 9.6-3 documents the data to be collected.  
 
Table 9.6-3: Testing to be collected at three month visit (V4) 
Data Collection 
Location of Source 
Average office BP Measurement per guidelines 
(including standing office BP) 
Maintain at site 
Home BP measurements and review of diary entries 
Maintain copy at site 
Physical examination  
Maintain at site 

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Changes in medication 
Maintain at site 
Adverse Events 
Original at site. Upload copy to database 
(SAE, SADE) 
Protocol Deviations 
Maintain at site 
 
 V5: Four Month Visit (120±7 days post procedure) 
Subjects will be required to return to the clinical center four (4) months post procedure during. 
Table 9.6-4 documents the data to be collected. 
Table 9.6-4: Testing to be collected at four month visit (V5) 
Data Collection 
Location of Source 
Average seated office BP Measurement per guidelines 
(including standing office BP) 
Maintain at site 
Home BP measurements and review of diary entries 
Maintain copy at site 
Physical examination  
Maintain at site 
Changes in medication 
Maintain at site 
Adverse Events 
Original at site. Upload copy to 
database (SAE, SADE) 
Protocol Deviations 
Maintain at site 
 
 V6: Five Month Visit (150±7 days post procedure) 
Subjects will be required to return to the clinical center five (5) months post procedure. Table 
9.6-5 documents the data to be collected. 
 
Table 9.6-5: Testing to be collected at five month visit (V6) 
Data Collection 
Location of Source 
Average office BP Measurement per guidelines 
(including standing office BP) 
Maintain at site 
Home BP measurements and review of diary entries 
Maintain copy at site 
Physical examination  
Maintain at site 
Changes in medication 
Maintain at site 
Adverse Events 
Original at site. Upload copy to database 
(SAE, SADE) 
Protocol Deviations 
Maintain at site 
 
 V7: Six Month Visit (180±7 days post procedure) 
Subjects will be required to return to the clinical center six (6) months post procedure. The six 
month visit marks the end of the period of blinding for all subjects and hypertensive medication 
changes can be made per the discretion of the investigator after this visit. The six month FU 
also marks the minimum point at which Control patients may cross-over to treatment. 
Investigators will be informed when cross-overs may occur. Table 9.6-6 documents the data to 
be collected. 
Table 9.6-6: Testing to be collected at six month visit (V7) 

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Data Collection 
Location of Source 
Average office BP Measurement per guidelines 
(including standing office BP) 
Maintain at site 
24-hour ABP report* 
Upload to core lab. Maintain copy of 
report at site 
Home BP measurements and review of diary entries 
Maintain copy at site 
Blinding Index (record prior to un-blinding subject) 
Maintain at site 
Urine (for chemistry – for both cohorts and drug 
screening Trio Cohort Only) 
Maintain at site 
Blood (for chemistry) 
Maintain at site 
Blood (plasma for biomarkers- Solo Cohort only- 
Optional test) 
Maintain at site 
12-lead ECG 
Maintain at site 
Renal duplex ultrasound 
Upload copy. Maintain copy of report at 
site 
Physical examination  
Maintain at site 
Changes in medication 
Maintain at site 
Adverse Events 
Original at site. Upload copy to database 
(SAE, SADE) 
Protocol Deviations 
Maintain at site 
 
*Note: in the event insufficient data is available following the 24-hr ABP recording to determine 
eligibility, the subject will be offered the opportunity to repeat the measurement  
 
 V8: Twelve Month Visit (360±14 days post procedure) 
Subjects will be required to return to the clinical center twelve (12) months post procedure. 
Table 9.6-7 documents the data to be collected. 
Table 9.6-7: Testing to be collected at twelve month visit (V8) 
Data Collection 
Location of Source 
Average office BP Measurement per guidelines 
(including standing office BP) 
Maintain at site 
24-hour ABP report* 
Upload to core lab. Maintain copy of 
report at site 
Home BP measurements and review of diary entries 
Maintain copy at site 
Urine (for chemistry) 
Maintain at site 
Blood (for chemistry) 
Maintain at site 
12-lead ECG 
Maintain at site 
Treated Subjects: renal CTA or MRA  
Upload copy. Maintain copy of report at 
site  
Physical examination  
Maintain at site 
Changes in medication 
Maintain at site 
Adverse Events 
Original at site. Upload copy to database 
(SAE, SADE) 
Protocol Deviations 
Maintain at site 
 

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 V9, V10, V11 & V12: Twenty-Four (720±30), Thirty-Six (1080±30), 
Forty-Eight (1440±60) & Sixty (1880±60) Month Visits  
Subjects will be required to return to the clinical center twenty-four (24), thirty-six (36), forty-
eight (48) and sixty (60) months post procedure. The sixty month visit marks the end of the 
study-defined period of FU for all subjects who have not elected to cross-over (if applicable, 
see Section 9.7). Table 9.6-8 documents the data to be collected. 
 
Table 9.6-8: Testing to be collected at 24, 36, 48 & 60 Month visit (V9, V10, V11, V12) 
Data Collection 
Location of Source 
Average office BP Measurement per guidelines 
(including standing office BP) 
Maintain at site 
Treated Subjects: Renal duplex ultrasound (24 & 36 
Month Only) 
Upload copy. Maintain copy of report at 
site 
Physical examination  
Maintain at site 
Changes in medication 
Maintain at site 
Adverse Events 
Original at site. Upload copy to database 
(SAE, SADE) 
Protocol Deviations 
Maintain at site 
 
 
Cross-Over to Treatment 
In the event that cross-over to treatment is authorized, clinical sites will be informed by the 
Sponsor. Subjects that elect to cross-over will be followed according to the following 
schedule:  
• Cross-over Baseline Evaluation (COV1) 
• Cross-over Procedure (COP2) 
• Cross-over Discharge (COD2) 
• Cross-over 1-month FU (COV2) 
• 2- month FU (COV3) 
• Cross-over 6 month FU (COV4) 
• Cross-over 12 month FU (COV5) 
• Cross-over 24 month FU (COV6) 
• Cross-over 36 month FU (COV7) 
• Cross-over 48 month FU (COV8) 
• Cross-over 60 month FU (COV9) 
 Cross-Over Data Collection 
The cross-over procedure should be conducted according to the detail in Section 9.4.6. The 
data to be collected during Cross-Over baseline is shown in Table 9.7-1 
 
Table 9.7-1: Data to be collected at Cross-over Baseline FU (COV1) 
Data Collection 
Location of Source 
Average office BP Measurement per guidelines (including 
standing office BP) 
Maintain at site 
Cross-over eligibility evaluation 
Maintain at site 

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24-hr ABP report*£ 
Maintain copy of report at site 
Limited physical examination including height, weight, brachial 
circumference; abdominal circumference; heart rate 
Maintain at site 
Current medications 
Maintain at site 
Baseline Blood (for chemistry)£ 
Maintain at site 
Baseline Urine (for chemistry) £ 
Maintain at site 
Negative Pregnancy test (within 7 days of procedure if 
applicable) 
Maintain at site 
Adverse Events 
Original at site. Upload copy to 
database (SAE, SADE) 
Protocol Deviations 
Maintain at site 
*Note: in the event insufficient data is available following the 24-hr ABP recording to determine 
eligibility, the subject will be asked to repeat the measurement. There cannot be more than 2 valid ABPM 
recordings performed within a maximum of 6 weeks to document uncontrolled BP. 
£ Results from tests recently performed during study follow-up visits may be used unless there were 
major changes to the patient condition or treatment.  
 
The data to be collected during Cross-Over procedure is shown in Table 9.7-2. 
 
Table 9.7-2: Data to be collected during the Cross-Over Procedure (COP2) 
Data Collection 
Location of Source 
Procedure times (femoral access to femoral closure) 
Maintain at site 
Procedural Medication (temporary anti-hypertensive medication; 
anesthesia; analgesia; anticoagulation if used; contrast volume 
etc.) 
Maintain at site 
Renal anatomy detail from renal angiogram (global or selective) 
Upload copy. Maintain copy of 
report at site 
Procedural angiogram 
Upload copy. Maintain copy at 
site  
Device and generator data including all accessories (guide 
catheters; guide wires) 
Maintain at site 
Paradise catheter usage; ultrasound ablation detail 
Maintain at site 
Adverse Events 
Original at site. Upload copy to 
database (SAE, SADE) 
Device Deficiencies 
Upload copy to database 
Protocol Deviations 
Maintain at site 
 
Hospital discharge should be conducted according to the detail in Section 9.5 other than the 
need for Pain Assessment and Blinding Index. Table 9.7-3 documents the data to be collected 
prior to discharge from the hospital for cross-over subjects 
 
Table 9.7-3: Data to be collected prior to Cross-over Discharge (COD2) 
Data Collection 
Location of Source 
Average office BP Measurement per guidelines (measurement of 
standing office BP is optional) 
Maintain at site 
Adverse Events 
Original at site. Upload copy to 
database (SAE, SADE) 
Protocol Deviations 
Maintain at site 
 
Subjects will be required to return to the clinical center one (1) month post cross-over 
procedure. Table 9.7-4 documents the data to be collected for cross-over subjects. 

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Table 9.7-4: Data to be collected at Cross-over 1 month FU (COV2) post cross-over 
procedure 
Data Collection 
Location of Source 
Average office BP Measurement per guidelines (including 
standing office BP) 
Maintain at site 
Adverse Events 
Original at site. Upload copy to 
database (SAE, SADE) 
Limited physical examination 
Maintain at site 
Changes in medication 
Maintain at site 
Protocol Deviations 
Maintain at site 
 
Ambulatory and office BP measurements should be recorded at the 2, 6 and 12 month FUs for 
all cross-over subjects. A CTA/MRA should be recorded in all cross-over subjects at the 12 
month FU. Table 9.7-5 documents the data to be collected at FU. 
 
Table 9.7-5: Data to be collected at 2, 6 & 12 month cross-over FUs (COV3, COV4, COV5) 
Data Collection 
Location of Source 
Average office BP Measurement per guidelines (including 
standing office BP) 
Maintain at site 
24-hour ABP report* 
Maintain copy of report at site 
Renal duplex ultrasound (2 & 6 month FU) 
Upload copy. Maintain copy of 
report at site 
Renal CTA or MRA (COV5- 12 Month FU Only) 
Upload copy. Maintain copy of 
report at site 
Limited physical examination 
Maintain at site 
Changes in medication 
Maintain at site 
Blood (for chemistry) 
Maintain at site 
Urine (for chemistry)  
Maintain at site 
Adverse Events 
Original at site. Upload copy to 
database (SAE, SADE) 
Protocol Deviations 
Maintain at site 
*Note: in the event insufficient data is available following the 24-hr ABP recording to determine 
eligibility, the subject will be asked to repeat the measurement. 
  
Table 9.7-6 documents the data to be collected at FUs. 
 
Table 9.7-6: Data to be collected 24- month, 36-month, 48-month & 60-month cross-over FU 
(COV6, COV7, COV8 & COV9) 
Data Collection 
Location of Source 
Average  office BP Measurement per guidelines (including 
standing office BP) 
Maintain at site 
Limited physical examination 
Maintain at site 
Changes in medication 
Maintain at site 
Renal duplex ultrasound (24 month & 36 month only) 
Upload copy. Maintain copy of 
report at site 
Adverse Events 
Original at site. Upload copy to 
database (SAE, SADE) 
Protocol Deviations 
Maintain at site 

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More frequent FU than those specified above are at the discretion of the Investigator and will 
be documented as unscheduled visits. 
 
Unscheduled Visits 
Unscheduled visits may occur at any time during the study for the assessment of for example, 
possible adverse events and/or medication changes. Each unscheduled visit will be documented. 
As part of the Unscheduled Follow-up, if any of the following assessments/procedures are 
performed, they should be reported in the database: Medical History; Physical Examination; 
Medications; Office Blood Pressure; Home Blood Pressure;  Ambulatory Blood Pressure;  12-
lead ECG;  Renal Duplex Ultrasound; Non-invasive imaging (CTA/MRA);  Urine Chemistry;  
Blood Chemistry;  Plasma for Biomarkers;  Pregnancy Test. 
 
Study Completion 
All patients will be followed for a minimum of 60 months post procedure unless otherwise 
informed by the Sponsor. Documentation of study completion will be required for all subjects 
independent of the point at which they complete the study (including screening failure, early 
withdrawal or loss to FU as applicable). 
 
 Extended Follow-up Period  
All subjects will be followed for five (5) years post procedure.   Subjects would be followed 
per standard of care for their Institution with continued adverse event collection and reporting. 
The information collected during these regular follow-up visits will be reported via the 
electronic data capture (EDC) system, as outlined in Tables 9.1-1, 9.1-2. 9.6-8 & 9.7-6.  DSMB 
review of clinical event information will continue to occur as specified in the DSMB charter.  
 Study Closure 
The point at which all subjects have completed the study will mark the point of study closure. 
The Sponsor will provide written documentation of study closure.    
 Study Medication 
Throughout the study, subjects will be instructed about the importance of medication adherence 
and asked to take any required study-defined antihypertensive treatment at approximately 
08:00am daily except on the morning of each office FU visit when they will be asked to bring 
their protocol-defined medication with them to the visit. This applies to subjects in the Trio 
cohort as well as any subjects that begin antihypertensive medication at any time during the 
study. 
 
At all times the safety and well-being of the subject are of primary concern. For the period of 
wash-out/run-in (RADIANCE Solo) or stabilization (RADIANCE Trio) prior to procedure, 
through to the 2 month Primary Efficacy endpoint visit, changes in medication outside the 
requirements of the study protocol may not occur other than:  
• As required to facilitate antihypertensive drug wash-out per standard Institutional 
guidelines  

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• In the incidence of a BP emergency associated with clinical events believed to be related 
to persistent or elevated hypertension 
• 
In the incidence of a clinical event that means a change in medication becomes 
necessary.  
Following the 2 month Primary Efficacy endpoint visit, all subjects will remain blinded up to 
the 6 month visit. After the 6 month FU visit subjects will be un-blinded and are eligible to be 
treated per physician discretion  
Between the 2 and 6 month FU visits, pre-defined escalation of antihypertensive medication is 
strongly recommended in both cohorts. The medication escalation will start at the FU where a 
sustained elevation (≥135 mmHg systolic OR ≥ 85mmHg diastolic) in 7-day home BP 
measurement is documented (confirmed by office BP ≥ 140 or ≥ 90 mmHg if required per Institutional 
practice).  Drugs will be added sequentially at each monthly FU in the event BP remains 
elevated. In the event BP remains <135/85 mmHg, no action is required. More frequent 
introduction of medication is permissible at the discretion of the Investigator in the event that 
BP remains ≥135 mmHg systolic or ≥ 85 mmHg diastolic. 
 
 RADIANCE Solo Cohort Study Medication 
Since the RADIANCE Solo cohort by definition remains free of antihypertensive medication 
through to the 2-month Primary Efficacy endpoint visit unless necessitated as described above 
and in Section 9.13, introduction of antihypertensive therapy may occur as needed following 
the measurement of the 2 month ABP. Introduction of antihypertensive medication should 
occur sequentially in the order indicated below in Table 9.12-1 unless otherwise medically 
indicated.  
Table 9.12-1: Solo Cohort Drug Escalation 
RADIANCE Solo Cohort 
Escalation Step 
Drug Class 
Recommended drugs 
0 
None 
NA 
1 
Long acting dihydropyridine CCB: mid 
dose 
Amlodipine: 5 mg 
2 
 ARB or ACEi: full dose 
ARB: Valsartan  160-320 mg; 
Olmesartan 20-40 mg 
ACEi: Ramipril 10-20 mg;  
Lisinopril 20-40 mg 
3 
Thiazide diuretic: low dose 
HCTZ 12.5 mg 
4 
Thiazide diuretic: full dose 
HCTZ 25 mg 
5 
Long acting dihydropyridine CCB: full dose 
Amlodipine 10 mg 
Note: All recommended doses are once daily 
 RADIANCE Trio Cohort Study Medication  
All subjects assigned to the RADIANCE Triple Cohort will have their current hypertensive 
medication regimen replaced* for a minimum of approximately 3 months starting with a 4- 
week stabilization period prescribed, to a single pill, fixed dose, triple combination, anti-
hypertensive medication of Amlodipine (10 mg); Valsartan (160 mg) or Olmesartan (40 mg) 
and Hydrochlorothiazide (25 mg). In the event of leg edema the Amlodipine dose can be 
reduced to 5 mg. This combination will be taken through to the two month Primary Efficacy 
endpoint FU visit. During this period, changes in antihypertensive medication may not occur 

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unless as described above and in Section 9.13. Introduction of additional antihypertensive 
therapy may occur as needed following the measurement of the 2 month ABP. Introduction of 
antihypertensive medication should occur sequentially in the order indicated below in Table 
9.12-2 unless otherwise medically indicated.  
 
*Note: Subjects with uncontrolled, treatment resistant hypertension currently prescribed to Tribenzor/Sevikar 
HCT or Exforge HCT (including generics) are eligible. Subjects will be followed for a 4 week stabilization period 
prior to confirming ABP according to the requirements of the protocol 
 
 
Table 9.12-2: Trio Cohort Drug Escalation 
RADIANCE Trio Cohort 
Escalation Step 
Drug Class 
Recommended drugs 
0 
None 
NA 
1 
Aldosterone antagonist 
Spironolactone: 25 mg 
2 
Long acting, cardioselective Beta-1 
receptor blocker: full dose 
Bisoprolol: 10 mg 
3 
Central Alpha-2 receptor agonist: full 
dose 
Clonidine: 0.1-0.2 mg; Rilmenidine: 
1-2mg;  Moxonidine 0.2-0.4  mg 
4 
Long acting Alpha-1 receptor blocker: 
full dose 
Slow release Prazosin 5-10 mg; 
Doxazosin 4-8 mg 
Note: All recommended doses are once daily other than for Clonidine, Rilmenidine or Moxonidine 
which should be added twice daily at their higher doses 
 
 Medication Changes due to BP Emergency 
At all times the safety and well-being of the subject are of primary concern.  
Since the aim of the RADIANCE-HTN study is to determine the effectiveness of renal 
denervation without medication changes confounding the results, it is intended that baseline 
hypertensive medication (or lack of it), be maintained through the Primary Efficacy endpoint 
visit which occurs two months after randomization. However in cases where medication 
changes are considered medically necessary (e.g. a significant change in BP or adverse events 
directly related to BP variations or BP medications), medication and/or doses may be adjusted 
according to the following guidelines: 
 Low BP Action 
The dosage of study-defined drugs can be reduced temporarily or discontinued permanently for 
any subjects whose office systolic BP is reduced to <110mmHg with associated signs and 
symptoms of hypotension or reduced renal perfusion or an increase in plasma creatinine ≥ 30%. 
The order in which antihypertensive drugs should be discontinued will depend upon the 
subjects’ assigned cohort (Solo or Trio) and the stage that they are within the scheduled FU. 
When medically appropriate, for all subjects in whom hypertension medication escalation has 
started since the 2 month FU visit, down-titration or discontinuation of hypertensive medication 
is recommended to follow the reverse order in which they have been added such that the last 
drug added should be first stopped (followed by the penultimate drug etc.). For subjects in the 
RADIANCE Trio cohort prescribed only to the single pill, fixed dose combination, reducing or 
stopping the current dose of HCTZ should be a first step with subjects then being switched to a 
double combination CCB + ARB (Sevikar® or Exforge®).   All changes in antihypertensive 
treatment will be documented and patient BP data will be included as per intention-to-treat. 

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 High BP Action 
Clinical intervention may be required for patients who have clinical adverse events felt to be 
related to persistent or elevated hypertension at any visit after randomization defined by average 
7 day home BP ≥170 (systolic) or ≥105 mmHg (diastolic) and subsequently confirmed by office 
BP ≥180 or ≥120mmHg (if confirmation is required per Institutional practice).  In these 
circumstances and assuming the subject is post-randomization, the treatment regimen should 
follow the hypertension medication escalation algorithm as described in Section 9.12.1 and 
9.12.2.   
In the event that a hypertensive emergency as defined above (i.e with associated clinical events 
felt to be related to persistent or elevated hypertension) is documented prior to randomization, 
the subject will be treated per Institutional guidelines and withdrawn from the study.   
All changes in antihypertensive treatment will be documented and patient BP data will be 
included as per intention-to-treat 
10. Study Defined Procedures/Testing 
 Office Blood Pressure Measurements 
All clinical sites will be provided with an office BP system (either the Omron® MIT ELITE 
Plus or M10-IT, Omron Co., Kyoto, Japan-). In the event either of these devices becomes 
unavailable during the course of the study, a commercially equivalent model may be 
substituted).  The same model must be used for any given subject throughout the course of the 
study.  It is also recommended that the office BP system used to collect the V0 screening 
measurements be provided to the subject for the home BP measurements should they move 
forward (see Section 10.3). Measurement of office BP will occur at all clinic visits and at 
discharge and must be done by study personnel blinded to the subjects’ randomization. All 
efforts will be made to ensure that measurement of office BP is standardized at each visit under 
similar conditions including measurement from the same arm at same time of day using the 
same device by the same person.  
The measurement of office BP will be done according the following guidelines based on the 
2013 ESH/ESC Guidelines for the management of arterial hypertension and the JNC-7 2003 
Report on prevention, detection, evaluation and treatment of high BP:  
• Healthcare providers must ensure that devices for measuring BP are regularly inspected, 
properly validated, maintained and regularly recalibrated according to manufacturers’ 
instructions  
• The operator should be trained and regularly retrained in the standardized technique 
• Standardize the subjects’ environment and provide a relaxed, temperate setting, with the 
person quiet and seated, their feet on the floor and their arm outstretched at heart level 
and supported 
• Caffeine, exercise and smoking should be avoided for at least 30 minutes prior to the 
measurement 
• Allow the subjects to sit quietly in a chair for at least 5 minutes before beginning  
• If using an oscillometric semi-automated BP monitoring device, ensure that the device 
is validated and an appropriate cuff size for the person’s arm is used. The size of the 
bladder within the BP cuff must encircle at least 80% of the arm 
• Determine the arm which will be used for all blood pressure measurements. Women 
who have undergone a mastectomy should have blood pressure measured from the 

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opposite side to the mastectomy. For all others, take an initial BP measurement in both 
arms. Document and use the arm with the higher systolic reading. Ensure that the same 
arm is used at each FU. If the difference in readings is > 15 mmHg, repeat the 
measurements.  If the difference in readings between arms remains > 15 mmHg on the 
second measurement, measure subsequent blood pressures in the arm with the higher 
reading  
• For study defined BP measurements. Take three BP measurements, spaced 1–2 min 
apart, with the adapted cuff placed at the level of the brachial artery. You may add 
additional measurements if the three are quite different (>15 mmHg difference between 
highest and lowest). Document the average BP from the second and third measurements. 
In the event that more than three measurements are made, use the final two for the 
average BP calculation  
• BP will also be measured 1 min after resuming the standing position. Office heart rate 
will be determined using the same device 
 24-hour ABP Measurements 
The measurement of 24-hr ABP will occur at baseline, 2, 6 and 12 month FU visits.   
• Train subjects on the use of the ABP system (Microlife® WatchBP 03; Microlife, 
Taipei, Taiwan) and ask them to return approximately 24-hrs later with the ABP 
Monitor to download the ABP data (transport of ABP systems to the clinical center may 
be arranged at the discretion of the Investigator).  
• The ABP system will be provided by the clinical center to the subject with an 
appropriate cuff size for the person’s arm 
• The cuff will be attached to the patient’s non-dominant arm after they have had their 
office BP recorded. System set up (including choice and fitting of BP cuff) subject 
instructions for use will be included in the Manual of Operations   
• Instruct the subject that they may not remove the BP cuff during the 24-hr period of 
recording even when washing 
• Instruct the subject that during the period in which measurements occur, that they should 
relax their arm and try not to walk or speak  
• BP will be measured every 20 minutes during daytime (07:00-22:00 hours) and every 
30 min overnight (22:00-07:00 hours).  
• Only ABP recordings with a minimum of 21 measurements during the daytime period 
will be considered validxlix. In case of a non-valid measurement, a known or suspected 
technical failure of the ABPM device, patient non-compliance to the study requirements 
(e.g. removal of cuff during recording, sleeping during the daytime period etc), a new 
ABP recording can be performed preferably the next day. In the event a repeat ABPM 
will occur more than 2 days after the original recording, the Sponsor must be notified 
for agreement. 
 Home BP Measurements 
After education on the use of the Home BP system, all subjects will be provided with a Home 
BP monitor (Omron® M10-IT, Omron Co., Kyoto, Japan) during the visit at which they are 
assigned to either cohort. In the event that this device becomes unavailable during the course 
of the study, a commercially equivalent model may be substituted for new subjects.  Subjects 
will measure their BP at home during the 7 consecutive days prior to each scheduled office FU 
visit. It is recommended that the clinical site contact the subject to remind them when to begin 
their 7day Home BP monitoring. The Home BP monitors should be returned to the clinical 

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center in the event that a subject withdraws or is screened out at any time prior to randomization 
as defined in Sections 8.2 and 8.3.  The following guidelines for measuring home BP should be 
followed: 
• Measurements will be taken in a quiet room with the subject in a seated position, back and 
arm supported after at least 5 minutes of rest with the adapted cuff placed at the level of the 
brachial artery 
• Two BP measurements will be made after a period of at least 5 minutes rest, 1-2 minutes 
apart twice daily. The two measurements should be made once in the morning prior to eating 
and antihypertensive drug intake (if relevant) and in once the evening after eating. The time 
that BP measurements are made will be immediately documented in the patient diary 
• Ensure that the same arm is used for all Home BP measurements.  
• Home BP values will be calculated as the mean of all measurements taken after the first day 
which will be discarded. A minimum of 18 BP measurements are required for a valid 
reading 
 
To verify the patient diary entries, it is strongly recommended that the subject bring their home 
blood pressure device with them to every follow-up and that a report is collected directly from 
the device.  In the event of discrepancies between the diary and the stored report, the report 
should be considered primary source. 
 Standardized eGFR Calculation 
eGFR calculations for both inclusion and FU measurements will be standardized using the 
Modification of Diet in Renal Disease formula (GFR (mL/min/1.73 m2) = 175 x (Scr)-1.154 x 
(Age)-0.203 x (0.742 if female) x (1.212 if African American) (conventional units). Formulas may 
be adapted to allow for non-US conventions. Data collected on the case report form will allow 
automatic calculation of eGFR. 
 Non-Invasive Imaging (CTA/MRA) 
Evaluation of the kidneys to verify anatomical inclusion is required prior to the procedure using 
either standard Computed Tomographic Angiography (CTA) or Magnetic Resonance 
Angiography (MRA).  Any good quality renal CTA or MRA imaging with arterial phase 
contrast that has been performed within 1 year of the subjects informed consent is considered 
eligible however if a CTA or MRA needs to be performed specifically for entry into the study, 
it should occur once ABP eligibility has been confirmed.  At a minimum, the site in 
collaboration with the Sponsor will perform and document an initial review of the image prior 
to the procedure. The Sponsor review is designed to allow recommendations for treatment 
strategy to be made prior to the procedure. A comparative renal CTA/MRA will be performed 
12 months after renal denervation. To ensure consistency around image collection, guidelines 
for completion of CTA/MRA imaging will be provided by the Sponsor (CLN 0019).  
 Non-Invasive Imaging (Renal Duplex Ultrasound) 
Non-invasive evaluation of the kidneys and renal anatomy during the progression of the study 
will be done on all subjects (in order to maintain blinding) at the 2 and 6 month FUs and in all 
treated subjects at the 24 and 36 month FUs, using renal duplex ultrasound. To allow for a direct 
comparator with images collected at follow-up, a baseline renal duplex ultrasound in addition 
to the requisite CTA/MRA is strongly recommended. In any event, at any time throughout the 
duration of the study, if there is any clinical indication or suspicion of any renal anatomical 

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abnormalities (such as high blood pressure that is extremely hard to control; worsening of 
previously well controlled blood pressure; elevated blood pressure that affects other organs in 
the body), diagnosis should be confirmed by a more sensitive imaging method such as 
CTA/MRA or angiogram.  To ensure consistency around image collection, guidelines for 
completion of non-invasive imaging will be provided by the Sponsor. 
 Laboratory Assessments 
All subjects will have blood collected at Baseline and 2, 6 and 12 month FU visits for full 
metabolic panel assessment (sodium, potassium, calcium, chloride, bicarbonate, glucose, uric 
acid, total protein, triglycerides, total cholesterol, HDL, HbA1C, blood urine nitrogen and 
serum or plasma creatinine (for use in the estimation of glomerular filtration rate- see Section 
10.4). Documentation may be provided to support any local or national differences in standard 
metabolic panel collection. In addition, all subjects will have urine samples collected at 
Baseline and 2, 6, and 12 month FU visits for urinalysis (sodium, potassium, protein, albumin, 
creatinine) and Trio Cohort subjects will have subsequent analysis of antihypertensive 
compliance. Females of child bearing potential will have a urine or blood plasma pregnancy 
test up to 7 days prior to the procedure. 
 HP LC-MS/MS of Antihypertensive Compliance 
HP LC-MS/MS is a recognized method with good to excellent sensitivity and specificity to 
detect many pharmacological agents in urine.l Urine collected for Trio subjects at Baseline, 2 
and 6 month FUs will be sent for analysis. Details of the analysis will be documented in the 
Manual of Operations. 
 Plasma Biomarkers- Optional Assessment 
There is emerging evidence that plasma biomarkers may help identify responders to renal 
denervationli,lii  Blood plasma may be collected at Baseline, 2, 6 and 12 month FUs and stored 
at a minimum of -20oC for subsequent analysis of the following biomarkers.  
• Plasma Immunoreactive Renin  
• Aldosterone 
• Brain Naturetic Peptide (BNP) 
• NT-proBNP  
• Copeptin  
• Glucose 
• Insulin 
• HbA1C 
• Endothelin-1  
11. Data Collection and Statistical Analysis 
 Data Collection, Processing, and Review 
Subject data will be collected via a limited access, secure, electronic data capture (EDC) system 
meeting the requirements of 21 CFR part 11. Paper case report forms (CRFs) may be used as a 
back-up in the event that the EDC system becomes unavailable. Electronic and/or written 
signatures will be collected in compliance with local regulations. Data processing will be 

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performed in compliance with the EU General Data Protection Regulation (GDPR) 2016/679, 
and all applicable national laws. 
Visual and/or electronic data review will be performed to identify possible data discrepancies. 
Manual and/or automatic queries will be created in the EDC system if used and will be issued 
to the clinical site for appropriate response.  
In the event that any data has to be collected on paper CRFs, the clinical site will be required to 
re-enter the same data into the EDC system should it become subsequently available.  The 
clinical site will record data on outcome variables as well as adverse events should they occur.  
Subject confidentiality will be maintained and each subject will be identified by his or her 
subject number.  Subject names will not be published. 
 
Each data field completed via an EDC system (either paper CRF) is expected to have a 
verifiable source document. Appropriate source documents include but are not limited to:  
• Patient information sheet and consent form 
• Subject Medical Record 
• Screening logs 
• Laboratory or core lab reports 
• Cath Lab or Operating Room reports 
• Angiograms; CTAs; MRAs 
• Documentation of serious adverse events 
• Worksheets (recommended to only be for collection of data points that have no other 
verifiable source) 
 Statistical Analysis 
Any details of statistical analysis not included in the protocol, can be found in the Statistical 
Analysis Plan.  The primary analysis will be based on the intent to treat population, with 
subjects analyzed according to their original randomization assignment. 
 Primary Efficacy Endpoint 
The mean difference between randomized groups for the change in daytime ambulatory systolic 
BP at 2 months post-procedure will be compared via a linear regression (ANCOVA) model 
adjusted for subjects’ baseline daytime ambulatory systolic BP. In mathematical formulation, 
the statistical hypothesis test will be based on the following: 
 
Ho: βtxt = 0 
Ha: βtxt ≠ 0 
 
Where βtxt is the regression coefficient for the treatment versus control term from the following 
linear model: 
 
Y = β0 + βtxt*Xtrt + βbl*Xbl 
 
Where  

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• Y = the reduction in ambulatory systolic BP from baseline to 2 months post-procedure  
• βtxt = the regression coefficient associated with the treatment term 
• Xtrt = a indicator variable for treatment group, with a value of 1 for the treatment group 
and 0 for the control group 
• Βbl = the regression coefficient associated with the baseline ABP 
• Xbl = the baseline ABP 
 
For patients with missing FU ABP values, a value of zero will be used in the analysis; this 
corresponds to imputing the baseline value. Additional details regarding the Primary Efficacy 
endpoint will be provided in the Statistical Analysis Plan. 
 Secondary Efficacy Endpoint 
The statistical analysis of the secondary efficacy endpoints will follow the methodology of the 
primary Efficacy Endpoint but will be based on daytime diastolic ABP; 24-hr ambulatory 
systolic and diastolic BP; night-time ambulatory systolic and diastolic BP. 
 Safety Assessments 
The assessment of safety will be based primarily on the frequency of serious adverse device 
effects (SADEs) serious adverse events (SAEs), adverse device effects (ADEs), adverse events 
(AEs) and laboratory abnormalities classified by Investigators as related to the renal 
denervation and confirmed by the DSMB. Occurrence and frequency of SADEs and ADEs and 
AE(s) and SAE(s) will be summarized by treatment group at baseline, last visit and by changes 
from baseline to last visit for laboratory values. Other safety data will be summarized as 
appropriate.  
 Observational Assessments 
For continuous measures, the linear model methodology of the Primary Efficacy endpoint will 
be applied. For categorical variables, binomial proportions and their corresponding exact 95% 
confidence intervals will be calculated. Differences between proportions will be assessed via 
Fisher’s exact test. Nominal p-values will be used without adjustment for multiple comparisons. 
Additional exploratory analyses may be performed 
 Control of Systematic Error/Bias 
Minimizing potential sources of bias has been taken into consideration in study design. To 
minimize selection bias, subjects will be randomly assigned to treatment or blinded control only 
after completion of all screening and eligibility procedures. Randomization will be generated 
by computer and stratified by center using blocks of small size and treatment permutation. 
Randomization in the Trio Cohort will also be stratified by beta blocker usage. 
 Limits on Subjects Enrollment 
Enrollment at any single clinical center will be limited to 20% of the maximum enrollment per 
cohort in order to prevent a single center from unduly influencing the study results. In addition, 
approximately 50% of subjects may be enrolled in clinical centers outside the United States. 
Clinical centers will be informed in writing by the Sponsor when they have met any of the 
enrollment limits. 

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 Planned Interim Analyses  
No formal interim analyses are planned for the purpose of stopping this study early for declaring 
effectiveness or for futility. Interim datasets will be provided to the DSMB for the purposes of 
review of safety and risk benefit. 
 Subgroup Analyses 
While no differences in results are expected for any of the defined subgroups, Primary and 
Secondary endpoint results by these subgroups will be examined. Details of these analyses will 
be described in the Statistical Analysis Plan. Additional exploratory subgroup analyses may be 
performed. 
 Multivariable Analyses 
The primary analysis of the Primary Efficacy endpoint will be based on a linear model with 
terms for randomized treatment group and baseline BP. Additional exploratory analyses may 
be performed. 
 
 Core Laboratories 
Core laboratories or independent experts will be used to assess and centralize non-invasive 
imaging, ABP, urine (for drug adherence measurements) and plasma (for the optional 
biomarker measurements). Specific details related to the core laboratories will be provided in 
separate Manuals of Operations. 
 
 Non-invasive Imaging Core Lab 
A core laboratory/independent expert may be used to evaluate any non-invasive imaging 
collected by CTA /MRA or duplex ultrasound at any time throughout the study. Independent 
experts will review all follow up CTA/MRA triggered by the renal duplex ultrasound imaging, 
and for all CTA/MRA collected at 12 months on subjects randomized to treatment,  The core 
lab will not be used to initially determine eligibility per the requirements of appropriate renal 
anatomy but may be used to: 
• Verify subject renal anatomy including the incidence, percentage and progression of renal 
artery stenosis and other renal artery anatomy abnormalities. Subjects with evidence of any 
renal artery anatomy anomalies that are outside the protocol inclusion/exclusion criteria will 
be documented as ineligible for randomization in any per protocol analysis.  
 
Ambulatory Blood Pressure Core Lab (dabl Ltd) 
Details of the core lab that will be used for configuration, distribution, training and 
centralization of data collection for 24-hr ABP measurements taken at Baseline, 2, 6 and 12- 
month FUs are provided below: 
dabl Ltd, 
Carraig Court,  
Georges Avenue,  
Blackrock,  
Co. Dublin,  
Ireland 

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T: +353 (0) 1 278 0247 
F: +353 (0) 1 278 0882 
www.dabl.eu 
 
Urine and Plasma Core Lab (CIC1418) 
Details of the core lab that will be used to evaluate antihypertensive drug adherence and 
plasma biomarker analysis are provided below: 
CIC1418 
Hôpital Européen Georges Pompidou,  
Laboratoire du Centre d'Investigation Clinique, 5ème étage pôle D 
20-40 Rue Leblanc, 75015 PARIS, France 
Phone : +33 (0) 1 56 09 26 55 
 
12. Safety Reporting 
 Definitions and Classification 
Adverse Events (AEs) are classified as per ISO:14155:2011 as “any untoward medical 
occurrence, unintended disease or injury, or any untoward clinical signs (including an abnormal 
laboratory finding) in subjects, users or other persons, whether or not related to the 
investigational medical device”.  All AEs will be collected for the duration of the study and will 
be further classified as anticipated or unanticipated using the known risks associated with the 
study device documented in Section 13.  AE classification will be according to the following 
definitions as provided in Table 12.1-1.  
Table 12.1-1: Adverse Event Definitions 
Term 
Definition 
Adverse Event (AE) 
 
Ref: ISO 14155-2011 
Any untoward medical occurrence, unintended disease or injury, or any 
untoward clinical signs (including an abnormal laboratory finding) in 
subjects, users or other persons, whether or not related to the investigational 
medical device.  
NOTE 1: This includes events related to the investigational medical device 
or comparator. 
NOTE 2: This definition includes events related to the procedures involved 
(any procedure in the clinical investigation plan). 
NOTE 3: For users or other persons, this definition is restricted to events 
related to the investigational medical device.  
Adverse Device Effect (ADE) 
 
Ref: ISO 14155-2011 
Adverse event related to the use of an investigational medical device 
NOTE 1: This definition includes any adverse event resulting from 
insufficient or inadequate instructions for use, the deployment, the 
implantation, the installation, the operation, or any malfunction of the 
investigational medical device. 
NOTE 2: This definition includes any event resulting from use error or 
from intentional misuse of the investigational medical device. 
NOTE 3:  This definition includes any event that occurs during the renal 
denervation procedure including the renal angiogram 
Serious Adverse Event (SAE) 
 
Ref: ISO 14155-2011 
Adverse event that: 
• Led to death, 
• Led to  serious deterioration in the health of the subject, that either 
resulted in: 

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Table 12.1-1: Adverse Event Definitions 
Term 
Definition 
o a life-threatening illness or injury, or 
o a permanent impairment of a body structure or a body function, or 
o in-patient  or prolonged hospitalization of existing hospitalization, or 
o medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function 
• Led to fetal distress, fetal death, or a congenital abnormality or birth 
defect. 
NOTE 1: Planned hospitalization for a pre-existing condition, or a 
procedure required by the clinical investigational plan, without serious 
deterioration in health, is not considered a serious adverse event.  
Serious Adverse Device Effect 
(SADE) 
Ref: ISO 14155-2011 
Adverse device, or procedure related, effect that has resulted in any of the 
consequences characteristic of a serious adverse event. 
Unanticipated Adverse Device 
Effect (UADE) 
 
Ref: 21 CFR Part 812 
 
 
Any serious adverse effect on health or safety or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or degree 
of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or welfare 
of subjects. 
Unanticipated Serious Adverse 
Device Effect (USADE) 
 
Ref: ISO 14155-2011 
 
 
Serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the current version of the risk analysis 
report. 
NOTE 1: Anticipated serious adverse device effect (ASADE) is an effect 
which by its nature, incidence, severity or outcome has been identified in the 
risk analysis report. 
 
Underlying diseases/ pre-existing conditions will not be reported as an AE unless there has been 
a substantial increase in the severity or frequency of the problem which has not been attributed 
to natural history during the course of the investigation.  
Death should not be documented as an AE, but should only be reflected as an outcome of a 
specific SAE (see Table 12.1-1 for AE definitions).  
Any AE experienced by the study subject after informed consent, whether during or subsequent 
to the procedure, must be recorded (EDC and/or paper CRF). 
 Relationship to Study Device(s) or Procedure 
The Investigator will assess the relationship of any AE to the study device or study procedure 
as related or unrelated. In the event of any discrepancy with respect to the relationship (e.g. 
during internal, independent adjudication, or DSMB review), the site may be queried for 
clarification.  AEs deemed to be specifically related to use of the study device (e.g. renal artery 
dissection or perforation, new onset renal stenosis) will be reported separately from AEs related 
to the procedure but not specific to renal denervation (e.g. anesthesia-induced nausea; allergy 
to contrast etc.). Criteria for determining whether an AE is related or unrelated to the study 
device are shown in Table 12.2-1:  

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Table 12.2-1: Criteria for Assessing Relationship of Study Device to AE 
Classification 
Description 
Unrelated 
The AE is determined to be due to a concurrent illness or effect of another device/drug 
and is not related to the investigational product. 
Related 
• The AE is determined to be potentially related to the investigational product, and 
an alternative etiology is equally or less likely compared to the potential 
relationship to investigational product, or 
• There is a strong relationship to investigational product, or recurs on re-challenge, 
and another etiology is unlikely, or 
• There is no other reasonable medical explanation for the event. 
Unknown 
• There is no clear evidence to support that the AE is related to the device  
 ReCor Medical Device Deficiencies 
Device deficiencies related to the use of ReCor Medical products may occur in the absence of 
any associated AE but must still be reported. The definition of a potential device deficiency is 
provided in Table 12.3-1.  
Table 12.3-1: Device Deficiency Definition 
Term 
Definition 
Device Deficiency 
 
Ref: ISO 14155-2011 
A device deficiency is any inadequacy of a medical device with respect to 
its identity, quality, durability, reliability, safety or performance. 
NOTE 1: Device deficiencies include malfunctions, misuse or use errors, 
and inadequate labeling. 
 
All device deficiencies (including but not limited to failures, malfunctions, use errors, product 
nonconformities, and labeling errors) will be documented and reported to the Sponsor within 2 
business days of notification. If possible, the device(s) and all associated accessories will be 
returned to the sponsor for analysis. Instructions for returning the clinical device(s) will be 
provided. If it is not possible to return the device, the investigator should document why the 
device was not returned and the final disposition of the device. Device failures and malfunctions 
should also be documented in the subject’s medical record. 
In the event that a device deficiency is associated with an AE that specific event would be 
recorded as an AE. 
Note: any Device Deficiency that might have led to an SAE if a) suitable action had not been 
taken or b) intervention had not been made or c) if circumstances had been less fortunate is 
considered reportable and should be notified to ReCor Medical within the timeframe noted. 
 Investigator Reporting Responsibilities 
The timelines for reporting AEs and device deficiencies to ReCor Medical are shown in Table 
12.4-1. 
Table 12.4-1: Investigator Reporting Requirements 
Event Classification 
Communication Method 
Communication Timeline 
Unanticipated Adverse Device 
Effect / Unanticipated Serious 
Adverse Device Effect  
Complete AE CRF page with all 
available new and updated information.  
In the absence of access to the EDC 
• 
Within 1 business day of first 
learning of the event  

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Table 12.4-1: Investigator Reporting Requirements 
Event Classification 
Communication Method 
Communication Timeline 
system, an email to ReCor medical with 
all 
available 
information 
is 
recommended 
Serious 
Adverse 
Event 
including 
Serious 
Adverse 
Device Effects 
Complete AE CRF page with all 
available new and updated information.  
• 
Within 2 business days or 
sooner (if required by 
local/regional regulations) of 
first learning of the event 
Device Deficiencies  
Complete Device Deficiency CRF page 
with all available new and updated 
information.  
• 
Within 2 business days of first 
learning of the event or as per 
local/regional regulations 
Adverse Device Effect 
Complete AE CRF, which contains 
such information as date of AE, 
treatment of AE resolution, assessment 
of seriousness and relationship to the 
device.  
• 
Within 10 business days or 
sooner (if required by 
local/regional regulations) of 
first learning of the event 
Adverse Event  
Complete AE CRF, which contains 
such information as date of AE, 
treatment of AE resolution, assessment 
of seriousness and relationship to the 
device. 
• 
Within 30 business days or 
sooner 
 
 Reporting to Regulatory Authorities / IRBs / ECs / Investigators 
 Sponsor Responsibilities 
The Sponsor is responsible for reporting all clinical events (including UADEs, SADEs and 
SAEs) reported by Investigators to applicable regulatory agencies as required by 21 CFR 
812.150(b), ISO 14155, and any other applicable geographies’ requirements. In addition the 
Sponsor is responsible for periodic progress reports to all reviewing IRBs/ECs, participating 
investigators and regulatory authorities, as appropriate and required per local/national 
regulations 
 Investigator Responsibilities 
The Principal Investigator is responsible for informing the Sponsor and the reviewing IRB/EC 
of all UADE’s, SADEs and SAE’s in line with the protocol and as required by local/national 
regulations. 
13. Potential Risks and Benefits 
 Risks Associated with the Study Device(s)  
There are potential (anticipated) risks associated with the use of the Paradise system. These 
risks may be serious or non-serious and include but are not limited to:  
• Ablation or thermal injury to vessel, adjacent tissue or other structures from energy 
application 
• Abdominal pain 
• Acute kidney injury 
• Adverse drug reaction 

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• Allergic reaction (drug, contrast, device or other) 
• Angina pectoris 
• Anxiety 
• Arrhythmia 
• Atrial tachycardia 
• Arteriovenous fistula 
• Arterioenteric fistula 
• Bleeding 
• Bradycardia 
• Cardiopulmonary arrest 
• Complications related to pain and anti-anxiety medication protocol 
• Complications related to anesthesia/monitored anesthesia/conscious sedation 
• Death 
• Deep vein thrombosis 
• Diarrhea 
• Dizziness/Syncope/Weakness  
• Edema 
• Embolism (air, plaque, thrombus, device or other) 
• Headache  
• Hematoma 
• Hematuria 
• Hemorrhage 
• Hyperhydrosis 
• Hypertension, including hypertensive crisis  
• Hypotension, including orthostatic hypotension 
• Infection 
• Myocardial infarction (MI) 
• Nausea 
• Pain (back, access site) 
• Pulmonary embolism 
• Pseudoaneurysm 
• Renal artery aneurysm or pseudoaneurysm 
• Renal artery dissection, or perforation 
• Renal artery stenosis or acceleration of atherosclerotic disease 
• Renal failure or renal insufficiency 
• Renal infarction (including due to embolization of plaque or coagulated/charred blood or 
tissue) 
• Sepsis  
• Stroke 
• Transient ischemic attack and/or Cerebrovascular accident   
• Urinary tract infection 
• Vasospasm 
• Ventricular tachycardia 
• Vessel trauma (perforation, dissection, or rupture) 
• Vessel thrombosis or occlusion 
• Vomiting 

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 Risks associated with Percutaneous Arterial Catheterization 
There are known (anticipated) risks associated with the arterial catheterization procedure not 
specific to the renal denervation system. These risks may be serious or non-serious and include 
but are not limited to:  
• General complications 
o Cardiorespiratory arrest 
o Severe arrhythmias or cardiac conduction defects 
o Acute coronary syndrome 
o Acute heart failure 
o Hypertensive crisis 
o Stroke from any cause 
o Pulmonary embolism 
o Acute renal insufficiency, hemodialysis 
o Doubling of serum creatinine 
o Retro-peritoneal hemorrhage/hematoma 
o Severe allergy to contrast agent 
o Infection 
o Allergic reaction 
o Hypotension 
o Mild disturbances of heart rate or cardiac conduction 
o Proteinuria, hematuria, electrolyte disturbances 
o Fever 
• Arterial complications associated with catheterization of the renal arteries 
o Embolism, infection 
o Stenosis or aneurysm 
o Dissection/perforation 
o Arterio-venous fistula or pseudoaneurysm 
o Need for revascularization by bypass surgery or angioplasty, stenting or surgery 
o Arterial spasm 
• Arterial complications associated with catheterization of the Aortic or illio-femoral arteries 
o Embolism and/or thrombosis 
o Dissection/perforation 
o Peripheral ischemia 
o Cholesterol embolism 
o Need for revascularization by bypass surgery or angioplasty, stenting or surgery 
• Femoral/Vascular access site complications 
o Arterial dissection/rupture 
o Access site hematoma/hemorrhage  
o Arterio-venous fistula  
o Pseudoaneurysm  
o Need for arterial bypass surgery 
o Infection 
o Pain 
o Bruising  
o Swelling 

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 Risks Associated with Participation in the Clinical Study 
There may be additional risks associated specifically with participation in the RADIANCE-
HTN clinical study. These risks are primarily associated with the additional testing associated 
with the study design and include but are not limited to: 
• Risks associated with blood draw  
• Risks associated with non-invasive imaging and risk of radiation exposure including 
potential teratogenic damage, if pregnant 
• Risks associated with the discontinuation of antihypertensive drug therapy  
• Risks associated with prescription of single pill, triple combination therapy composed 
of Amlodipine, Valsartan or Olmesartan and HCTZ (refer to manufacturers brochures 
for details)  
• Risks associated with the use of any Blood Pressure Monitoring system such as bruising, 
pain or skin rash related to the cuff 
• Risks associated with a 12-lead ECG including a skin rash 
 Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through appropriate training, compliance 
with this protocol, performing procedures in the appropriate hospital environment, adherence 
to subject selection criteria, close monitoring of the subject's physiologic status during research 
procedures and/or FUs and by promptly supplying ReCor Medical with all pertinent 
information required by this protocol.  In addition specific measures have been taken to 
minimize the risk for all subjects including: 
• Drug discontinuation in the RADIANCE Solo cohort will occur in line with accepted 
guidelines for a subjects’ current medication and subjects whose baseline eligibility 
systolic/diastolic office BP is ≥180/110 mmHg or baseline daytime ABP is ≥170/105 
mmHg are excluded.   
• Drug discontinuation in the RADIANCE Solo cohort is limited to a short period of 
approximately 3 months during which timeframe subjects are a low risk of any CV event 
off treatment 
• All subjects will be provided with home BP monitoring devices from the point of a) 
drug discontinuation or run-in (RADIANCE Solo cohort) or b) initiation of fixed dose 
triple combination therapy (RADIANCE Trio Cohort).  
• Subjects whose average home BP increases to ≥170 systolic or ≥105 mmHg diastolic 
and who have clinical events considered to be related to persistent or elevated 
hypertension pre-randomization such that a change in medication is necessitated, will 
be excluded 
• Subjects whose average home BP increases to ≥170 systolic or ≥105 mmHg diastolic at 
any time post randomization will be eligible to have their anti-hypertensive medication 
restarted or modified as needed  
• Subjects in the RADIANCE Solo cohort will have anti-hypertensive drug therapy 
initiated immediately following the 2 month FU if needed 

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• Non-invasive imaging will be required for all subjects at baseline (CTA/MRA at a 
minimum) and at the 2 and 6 month FUs (duplex ultrasound) and for all treated subjects 
at the 12 month FU (CTA/MRA) and the 24 and 36 month FUs (duplex ultrasound) 
 Anticipated Benefits 
Subjects included in the RADIANCE-HTN Study may benefit from closer evaluation of their 
hypertension via frequent office FU, home and 24-hr ABP measurements. They may also 
benefit from having diagnostic non-invasive and invasive evaluation of their renal anatomy in 
the event of previously undiagnosed renal abnormalities or stenosis. There is potential that 
subjects may have their hypertension reduced without the need for medication.  There may be 
no benefit to subjects. 
 Risk to Benefit Rationale 
Catheter based renal denervation is an interventional approach to treat patients with essential 
hypertension by interrupting the renal sympathetic nerve signaling pathways.  Chronic 
elevation in sympathetic activity contributes to the development of chronic hypertension, and 
potential end organ damage.  Chronic essential (primary) hypertension is a major public health 
burden with a global prevalence of 1 billion, and a US prevalence of approximately 76 million.   
Hypertension is considered to be a major risk factor for cardiovascular diseases, specifically 
stroke, myocardial infarction, heart failure, and renal failure, and accounts for approximately 9 
million deaths worldwide annually.   Despite the associated morbidity and mortality, BP control 
remains a challenge globally in part due to issues of non-compliance to prescribed medications.   
The premise is that ablation of renal sympathetic nerves will lead to a decrease in BP either as 
an adjunct to pharmacologic therapy, or potentially as a replacement of escalating 
pharmacologic therapy.  Incremental reductions in BP are known to decrease the incidence of 
major cardiovascular events. Reducing systolic BP by as little as 5 mmHg has been shown to 
be associated with a 14% reduction in the incidence of stroke, a 9% reduction in the incidence 
of cardiovascular disease and a 7% reduction in mortality 
The use of ultrasound energy to ablate the nerves may provide for a safe and effective approach 
to decrease blood pressure through renal nerve denervation.   The Paradise System has been 
designed to maximize safety while ablating the nerves in a circumferential pattern to effectively 
ablate the majority of the renal sympathetic nerves.  Ultrasound energy offers distinct 
advantages over other energy sources since direct tissue contact is not required, and the energy 
profile is controllable.  The Paradise System has been designed to deliver energy for a short 
duration, at a target mean depth of 1-6 mm to ablate the renal sympathetic nerves located in the 
adventitia and peri-adventia while preserving the integrity of the renal arterial wall (0-1 mm) 
and by preventing thermal injury to non-target tissues at depth (maximum depth >10mm).    
Preclinical studies confirm the target ablation profile is consistently achieved with effective 
nerve ablation and minimal to no injury to non-target tissues. 
The clinical procedure is a standard interventional cardiology procedure that can be performed 
quickly with minimal injury to non-target tissues.  Ablation of nerves can be painful however 
the procedure is tolerable with appropriate analgesic medication.   The Paradise System has 
been evaluated in multiple clinical studies with few AEs reported specifically related to the use 
of the investigational system.  Office and ambulatory BP has been reduced in a majority of 
patients.    The benefit to patients in terms of reduction of cardiovascular events will need to be 
determined over a long duration however there is notable short-term benefit associated with the 
procedure in a majority of patients.  Many patients experience large decreases in ABP, and in 

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certain cases a concomitant decrease in antihypertensive medication.  The procedure risks are 
limited to short-term pain, and standard angioplasty catheter related risks.  Ultrasound provides 
for a safe means to ablate renal sympathetic nerves that should provide a benefit to patients with 
chronic essential hypertension in terms of BP reduction. 
14. Protocol Deviations 
The study protocol is to be followed at all times by Investigators and all personnel involved in 
the clinical study. The exception is in the event of an emergency deviation initiated by the 
Investigator in the case where a change is needed to eliminate the apparent hazard to subjects. 
Emergency deviations must be reported to ReCor Medical no later than 24 hours following the 
emergency.  
All deviations from the protocol will be documented (via EDC system and/or on CRF) and will 
be classified according to the categories below in Table 13.6-1: 
  
Table 13.6-1: Deviation Classifications 
Deviation 
Classification 
Definition of Deviation 
Timeline for 
Reporting           
(if applicable) 
Class Ia 
Deviation to protect the life or physical wellbeing of a patient in 
an unforeseen emergency 
Within 24hrs 
Class Ib 
Documented failure to obtain subject informed consent 
Within 24 hrs of notice 
Class II 
Deviation based on medical judgment to prevent harm to a 
patient in a non-emergency situation 
As soon as possible 
Class III 
Deviation due to lack of understanding of the protocol 
requirements (training is an issue) 
As soon as possible 
Class IV 
Deviation due to a situation that is beyond control 
As soon as possible 
Class V 
Deviation due to an oversight, error (training is not an issue) 
As soon as possible 
Class VI 
Comments; Deviations that do not meet any of the definitions 
listed above, including those for which the Sponsor provided a 
waiver. 
NA 
 
Deviations from the investigational plan and study requirements (including cGCP guidelines) 
will be reviewed and evaluated on an ongoing basis and appropriate corrective actions will be 
implemented as necessary.  
15. Protocol Amendments  
Changes to the study must be documented via a formal amendment process prior to 
implementation in the study. Amendments to the investigational plan may be initiated by ReCor 
Medical Inc. or at the request of the Investigator. A formal amendment cannot be initiated by 
an Investigator or clinical site personnel without the approval of ReCor Medical Inc. and the 
appropriate Local and National approvals including the documented approval of the 
Investigator.  

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16. Device/Equipment Accountability 
Per ISO 14155-2011, the investigational devices/equipment shall be controlled and used only 
in this clinical study and according to this clinical protocol. Tracking of subjects and device 
allocations will be performed during the study.  
The sponsor shall keep records to document the physical location of all study-related devices 
from shipment to the investigation sites until return or disposal.  It is recommended that the 
Paradise catheter and accessories used for each procedure be returned to the Sponsor.  If the devices 
are not returned, appropriate disposal must be documented. All unused investigational product will 
be returned to the Sponsor at the end of the study. 
 
The principal investigator or an authorized designee shall keep records documenting the receipt, 
use, return and disposal of the investigational devices/equipment, which shall include the 
following: 
• Date of receipt 
• Identification of each investigational device/piece of equipment (batch number or unique 
code) 
• Expiry date, as applicable 
• Date or dates of use 
• Subject identification 
• Date on which the investigational device/piece of equipment was returned/explanted from 
subject, if applicable 
• Date of return of unused, expired, or malfunctioning investigational devices/equipment, if 
applicable. 
17. Compliance 
 Statement of Compliance 
This study will be conducted in accordance with the declaration of Helsinki, ISO 14155: 2011 
and FDA 21 CFR parts 50, 54, 56, 812. The study shall not begin until appropriate National 
and Local approvals have been obtained, as appropriate. Any additional requirements imposed 
by the IRB/EC or regulatory authority shall be followed where appropriate. 
 Investigator Responsibilities 
The Principal Investigator of an investigational center is responsible for ensuring that the study 
is conducted in accordance with all Clinical Study Agreements, the clinical protocol, ISO 
14155:2011, ethical principles that have their origins in the Declaration of Helsinki, any 
conditions of approval imposed by the reviewing IRB/EC, and prevailing local and/or country 
laws and/or regulations, whichever affords the greater protection to the subject. In addition the 
Investigators are responsible for: 
• Ensuring that the study is conducted with the express approval of the Institution’s IRB/EC  
• Ensuring that conducting the study will not give rise to conflicts of interest 
• Informing the Sponsor in writing of the reason(s) for any withdrawal of any IRB/EC 
approval  

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• Ceasing the enrollment of subjects immediately in the event of the withdrawal of any 
IRB/EC approval  
• Ensuring that no subjects will be enrolled, without prior, written Approval to Enroll from 
the Sponsor  
• Agreeing to use their best efforts to satisfactorily complete the planned work and to 
comply at all times with accepted Good Clinical Practice 
• Informing the sponsor of any conditions under which prior research was terminated  
• Ensuring that informed consent is obtained appropriately and that the conditions of 
informed consent are complied with 
• Ensuring the appropriate completion of all CRFs (paper and/or EDC) with the 
understanding that certain records and reports may be submitted to regulatory agencies by 
the Sponsor to support regulatory submissions  
• Maintaining all records as described in the Protocol 
• Supporting a monitor/auditor (as applicable) in their activities  
• Informing the Sponsor of all adverse events and adverse device effects in a timely manner 
and informing the EC/IRB of any serious adverse device effects as applicable 
 Institutional Review Board/ Ethics Committee 
The study shall not begin until appropriate National and Local approvals have been obtained, 
as appropriate. Any additional requirements imposed by the IRB/EC or regulatory authority 
shall be followed where appropriate. 
A copy of the written IRB/EC and/or competent authority approval of the clinical protocol (or 
permission to conduct the study or appropriate equivalent) as well as IRB/EC approval of the 
Informed Consent Form, must be received by the Sponsor before recruitment of subjects into 
the study and shipment of investigational product/equipment. Prior approval must also be 
obtained for other materials related to subject recruitment or which will be provided to the 
subject. The Sponsor will provide a written “Approval to Enroll” to document the point at which 
all requirements for initial subject recruitment have been met. 
Annual IRB/EC renewals will be obtained throughout the duration of the study as required by 
local/country or IRB/EC requirements.  
 Sponsor Responsibilities 
All information and data sent to the Sponsor concerning subjects or their participation in this 
study will be considered confidential. Only authorized Sponsor personnel or a designated 
Sponsor representative will have access to these confidential records. Authorized regulatory 
personnel have the right to inspect and copy all records pertinent to this study. Study data 
collected during this study may be used by the Sponsor for the purposes of this study, 
publication, and to support future research and/or other business purposes. All data used in the 
analysis and reporting of this study will be without identifiable reference to specific subject 
name.  Authorized representatives of the Sponsor may be present at procedures and FUs to 
provide technical and study specific assistance and may assist with the collection of technical 
data via the use of Technical Source Forms (worksheets). Any data collected by the Sponsor 
representative will be verified and counter signed by the Investigator.  The Sponsor 
representative will not: 

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• Practice medicine 
• Provide medical diagnosis or treatment to subjects 
In accordance with the requirements of providing technical support during the procedure and 
FUs, the  Sponsors representative will not be blinded to randomization but will ensure that no 
information that in any way may un-blind the Sponsor, subjects or blinded clinical site staff, 
will be included in any reports (written or verbal). 
 Insurance  
Where required by local/country regulation, the proof and type of insurance coverage, taken by 
the sponsor for subjects in the study will be obtained. 
18. Monitoring  
Monitoring will be performed during the study to assess continued compliance with the protocol 
and applicable regulations. Monitoring will occur in line with the Study Monitoring Plan. 
 Study Monitor 
Study Monitors assigned to the RADIANCE-HTN study will fulfill the required Sponsor and 
monitor responsibilities. Monitors in collaboration with other Sponsor-designated personnel, 
will be responsible for reviewing the device accountability documentation and subject data as 
collected on CRFs or via an EDC system. The monitor will ensure that the clinical protocol has 
been approved by the IRB/EC and will assure ongoing compliance with clinical protocol.   
The Investigator/institution guarantees direct access to original source documents by Sponsor 
personnel, their designees, and appropriate regulatory authorities. 
In accordance with the requirements of role, study monitors will not be blinded but will ensure 
that no information that in any way may un-blind the Sponsor or blinded clinical site staff will 
be included in any reports (written or verbal) 
 Monitoring Procedures 
Monitoring visits to the clinical sites will be made periodically for the purpose of ensuring that 
Investigators and their staff understand and accept their defined responsibilities, assessing 
compliance with current GCP guidelines, evaluating clinical trial progress, assessing the 
continued acceptability of the clinical site facilities, assessing compliance with this 
investigational plan, and verifying the data recorded on CRFs or via an EDC system.  
The Sponsor will design the forms to be used for the collection and recording of data at the 
clinical site.  Investigators will be responsible for the timely completion and submission of these 
forms. 
• Investigators are to maintain all source documents as required by the clinical protocol 
including but not limited to laboratory results, CRFs, supporting medical records, informed 
consents and applicable electronic files. The source documents will be used at the regular 
monitoring visits to verify information submitted on the CRFs. Clinical monitoring will 
include review and resolution of missing or inconsistent results to assure the accuracy of 
the reported data.  Where any discrepancies are noted, they will be resolved with the 
Investigator and/or an individual designated by the Investigator.  Where the data is 

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incomplete, attempts will be made to obtain the missing data.  The source documents and 
any completed CRFs will remain at the clinical sites.   
Subject safety will be ensured by noting that the consent was properly documented, the 
investigational plan was followed, and that AEs were reported and followed-up as appropriate. 
The study Monitor will evaluate and summarize the results of each clinical site visit in written 
reports, identifying any repeated data problems with any Investigator and specifying 
recommendations for resolution of noted deficiencies. 
As required by the IDE regulations, the conduct and monitoring of the clinical investigation 
will be conducted in accordance with the Sponsor’s approved monitoring plan.  
19. Informed Consent 
All subject participation is voluntary and as such Informed consent shall be obtained in writing 
from all subjects or their legally authorized representative. The process of obtaining informed 
consent shall be documented before any procedure specific to the clinical investigation is 
applied to the subject. The informed consent form consists of an information form and an 
informed consent signature form which can either be combined into one document or separated 
into two documents. The Sponsor will provide a template informed consent form in local 
language at a level understandable to the subject which will be approved by the IRB/EC. 
Changes to the template are acceptable but will be reviewed and approved by the Sponsor.  In 
the event that new information becomes available during the course of the study that may 
significantly affect a subjects’ decision to continue participation in the study, it will be provided 
to all affected subjects in written form and may require that the subject re-sign and date an 
amended informed consent form or new informed consent form as applicable. Any changes to 
the informed consent form that occur during the course of the study will require approval by 
the IRB/EC.  
 Process of Obtaining Informed Consent  
Per ISO: 14155: 2011 The process of obtaining informed consent at a minimum shall include 
the following steps: 
 
• Ensure that the principal investigator or his/her authorized designee conducts the informed 
consent process 
• Include all aspects of the clinical investigation that are relevant to the subject's decision to 
participate throughout the clinical investigation 
• Avoid any coercion or undue improper influence on, or inducement of, the subject to 
participate 
• Not waive or appear to waive the subject's legal rights 
• Use native non-technical language that is understandable to the subject 
• Provide ample time for the subject to read and understand the informed consent form and 
to consider participation in the clinical investigation 
• Include personally dated signatures of the subject and the principal investigator or an 
authorized designee responsible for conducting the informed consent process 
• Provide the subject with a copy of the signed and dated informed consent form and any 
other written information 
• Show how informed consent will be obtained and recorded in special circumstances where 
the subject is unable to provide it him- or herself 

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• Ensure important new information is provided to new and existing subjects throughout the 
clinical investigation 
The above requirements shall also apply with respect to informed consent obtained from a 
subject's legally authorized representative. Informed consent may be given by the legally 
authorized representative only if a subject is unable to make the decision to participate in a 
clinical investigation. In such cases, the subject shall also be informed about the clinical 
investigation within his/her ability to understand.  
The original informed consent form will be maintained the clinical site. The subject will be 
provided with a signed and dated copy including any other written information.  
 
Failure to obtain subject consent is a deviation to the study protocol and will be reported by the 
Sponsor to the appropriate Local and National authorities in line with their reporting 
requirements.  
20. Committees/Boards 
 Adverse Event Review 
AEs will be collected and reviewed on a continuous basis. Adjudication of AEs will occur in 3 
stages:  
• Stage 1: Investigator review and initial adjudication at point of data entry 
• Stage 2. Sponsor review.  Sponsor may query Investigator adjudication in the event 
there are discrepancies with source.  
• Stage 3:  All events deemed to be potentially device and/or procedure related and/or 
potentially serious will be reviewed by an independent physician adjudicator.   
• Stage 4. DSMB review and adjudication. The DSMB will provide final, independent 
review of aggregate events i 
*Independent adjudication using persons qualified in the appropriate field may be used at any stage 
as required for appropriate review. 
 
In addition, events related to any safety criteria pre-specified in the study protocol, plus all 
unanticipated events, device- or procedure-related events and deaths, will be provided to the 
DSMB for subsequent review.  
 Data Safety Monitoring Board 
The RADIANCE Data Safety Monitoring Board (DSMB) is comprised of independent experts 
in hypertension, interventional radiology or cardiology and biostatistics. The DSMB will be 
responsible for the oversight, review of all relevant AEs including but not limited to: 
• All unanticipated events   
• All AEs pre-specified as part of the overall safety assessment (see Section 5.2.4)  
• All device- or procedure-related events (ADEs and SADEs) 
• Deaths 
 
During the course of the study, the DSMB will review accumulating safety data in order to 
monitor the incidence of protocol-defined events and other trends that would warrant 
modification or termination of the study. The DSMB may review accumulating effectiveness 
data to assess the overall benefit-risk of the study. Criteria under which efficacy data may be 

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un-blinded will be pre-defined and documented in the Statistical Analysis Plan, as will triggers 
related to specific AE rates that would warrant the stopping or termination of the trial.  
Responsibilities, qualifications, membership, and committee procedures will be outlined in the 
DSMB Charter.  
 Steering Committee 
The RADIANCE Steering Committee is comprised of senior clinical, medical and regulatory 
members of ReCor Medical Inc. as well as International physician investigator advisors and the 
study statistician as appropriate. The role of the Steering Committee is to overview the design, 
submission and conduct of the study. Steering Committee members may participate in the 
review and approval of all requests for data analysis, abstract and manuscript preparation, and 
submission however, ReCor Medical Inc. remains responsible for all decisions related to any 
such requests in line with approved study agreements. 
21. Suspension or Termination 
 Premature Termination of the Study 
ReCor Medical Inc. reserves the right to terminate the study at any stage but intends to exercise 
this right only for valid scientific or administrative reasons and reasons related to protection of 
subjects.  Investigators, associated IRBs/ECs, and regulatory authorities, as applicable, will be 
notified in writing in the event of study termination. 
Possible reasons for premature study termination include, but are not limited to, the following. 
• The occurrence of UADEs that present a significant or unreasonable risk to subjects 
enrolled in the study 
• An enrollment rate far below expectation that prejudices the conclusion of the study  
• A decision on the part of ReCor Medical Inc. to suspend or discontinue development of the 
device 
 Termination of Participation by Investigator/Withdrawal of IRB/ EC Approval 
Any investigator, or IRB/ EC involved in the RADIANCE-HTN study may discontinue 
participation in the study or withdrawal approval of the study, respectively, with suitable written 
notice to ReCor Medical Inc. Investigators, associated IRBs/ECs, and regulatory authorities, as 
applicable, will be notified in writing in the event of these occurrences. 
 Requirements for Documentation and Subject Follow-up 
In the event of premature study termination a written statement as to why the premature 
termination has occurred will be provided to all participating centers by ReCor Medical Inc. 
The IRB/EC and regulatory authorities, as applicable, will be notified. Detailed information on 
how enrolled subjects will be managed thereafter will be provided.  
In the event an IRB or EC terminates participation in the study, participating investigators, 
associated IRBs/ECs, and regulatory authorities, as applicable, will be notified in writing. 
Detailed information on how enrolled subjects will be managed thereafter will be provided by 
ReCor Medical Inc. 
In the event an investigator terminates participation in the study, study responsibility will be 
transferred to a co-investigator when possible or another authorized clinical Investigator.  In 

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the event there are no opportunities to transfer investigator responsibility; detailed information 
on how enrolled subjects will be managed thereafter will be provided by ReCor Medical Inc. 
The investigator must return all documents and investigational product to ReCor Medical Inc., 
unless this action would jeopardize the rights, safety, or welfare of the subjects. 
 Criteria for Suspending/Terminating a Study Center 
ReCor Medical Inc. reserves the right to stop the inclusion of subjects at a study center at any 
time if no subjects have been enrolled for a period beyond 3 months after the site has been 
granted Approval to Enroll, or if the center has multiple or severe protocol 
violations/noncompliance without justification and/or fails to follow remedial actions. 
In the event of termination of investigator participation, all study-related devices and 
equipment, as applicable, will be returned to ReCor Medical Inc. unless this action would 
jeopardize the rights, safety or well-being of the subjects. The IRB/EC and regulatory 
authorities, as applicable, will be notified. All subjects enrolled in the study at the center will 
continue to be followed per protocol-defined FU.  The Principal Investigator at the center must 
make provision for these FU visits unless ReCor Medical Inc. notifies the investigational center 
otherwise. 
22. Reporting and Publication Policy 
ReCor Medical Inc. is committed to the publication and dissemination of clinical study results.  
Any publication or presentation relating to the RADIANCE Study will require that ReCor 
Medical’s role as a sponsor or financial supporter is included. The final report of the conclusions 
of the study will be written within 12 months of the closing of the database at the end of the 
study.  The report will be signed by all study principal investigators and provided to all study 
investigators.  The study protocol will be registered at www.clinicaltrials.gov before the 
inclusion of any study subjects. 
23. Reimbursement and Compensation for Subjects  
Travel and other expenses incurred by subjects as a result of participation in the study may be 
reimbursed in accordance with pertinent country laws and regulations and per the study site’s 
regulations.   
24. Medicare Study Criteria (US Only) 
Access to clinical study data provides opportunities to conduct further research that may help 
advance medical science and improve patient care. This helps ensure the data provided by 
research participants are used in the creation of knowledge and understanding. To this end, as 
stated in Section 22. Reporting and Publication Policy, the study results on all pre-specified 
outcomes, including negative outcomes, will be submitted to ClinicalTrials.gov not later than 
one year after the study completion date, where the completion date is defined as the date that 
the final subject was examined or received an intervention for purposes of data collection for 
the pre-defined outcome measures. Results submission could be delayed if an extension is 
granted to the results submission deadline; however, the release of all results on pre-specified 
outcomes will be hastened if the study is terminated early.  
 
Subjects participating in the RADIANCE HTN study are eligible for antihypertensive drug 
therapy and following the general indications/contraindications for use of the Paradise Renal 

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Denervation System, will be identified from the general subject population. Therefore it is not 
anticipated the device under investigation will affect Medicare beneficiaries differently than it 
would the Medicare eligible patients found in the investigators general subject population. 
However, participation in the study may provide Medicare beneficiaries with early access to a 
novel, investigational ultrasound renal denervation device therapy that is not otherwise 
available commercially in the U.S. at this time. According to 2012 CMS report on chronic 
conditions liii, high blood pressure (Hypertension) affects 58% of the Medicare FFS population 
including 39.5% of beneficiaries under 65 years old and 59.1% of beneficiaries age 65 and 
older. Recent analyses of National Health and Nutrition Examination Survey (NHANES) data, 
have estimated the prevalence of resistant hypertension at 8.9 ±0.6% of the US hypertensive 
population in 2003-2008. A time-sequence comparison of NHANES data from 1998 through 
2008 suggests that, unlike hypertension, resistant hypertension is becoming more prevalent 
(e.g., 20.7% in 2005-2008), due to aging and increased obesity in the general populationliv.  
Because the prevalence of hypertension is known to increase with age along with the potential 
for resistant hypertension, the results of this study are expected to be generalizable to the 
Medicare eligible population primarily due to age (E.g., the 65 years and older population).  
25. Abbreviations and Definitions  
 Abbreviations 
Abbreviations are shown in Table 25.1-1.   
Table 25.1-1: Abbreviations 
Abbreviation/Acronym 
Term 
IRB 
Institutional Review Board 
EC 
Ethics Committee 
CRF 
Case Report Form 
FDA 
Food and Drug Administration 
FU 
Follow Up 
IDE 
Investigational Device Exemption 
UADE 
Unanticipated Adverse Device Effect 
CTA 
Computed Tomography Angiography 
MRA 
Magnetic Resonance Angiography 
BP 
Blood Pressure 
ABP 
Ambulatory Blood Pressure 
AE 
Adverse Event 
SAE 
Serious Adverse Event 
ADE 
Adverse Device Effect 
SADE 
Serious Adverse Device Effect 
eGFR 
Estimated Glomerular Filtration Rate 
DSMB 
Data Safety Monitoring Board 
EDC 
Electronic Data Capture 
HCTZ 
Hydrochlorothiazide 
ACEi 
Angiotensin Converting Enzyme Inhibitor 
ARB 
Angiotensin Receptor Blocker 
CCB 
Calcium Channel Blocker 
 
 

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26. Appendix A: Visual Analog Pain Scale 
 
 
 
 

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27. References  
 
i Mancia G et al. Reappraisal of European Guidelines on hypertension management: A 
European Society of Hypertension Task Force Document. 2009. J Hypertens. 27: 2121-2158 
ii Chobanian AV et al. JNC 7- Complete Version. Seventh report of the Joint National 
Committee on prevention, detection, evaluation and treatment of high blood pressure. 2003. 
Hypertension. 42: 1206-1252 
iii A Global Brief on Hypertension: Silent Killer, global public health crisis. World Health 
Organization 2013 
iv Mancia G et al.  2013 ESH/ESC Guidelines for the Management of Arterial Hypertension: 
The Task Force for the Management of Arterial Hypertension of the European Society of 
Hypertension (ESH) and of the European Society of Cardiology (ESC). 2013.  J Hypertens. 
31:1281-357 
v Epstein BJ et al., Management of hypertension with fixed dose triple combination treatments. 
2013. Ther Adv Cardiovasc  Dis. 7: 246-259 
vi Baroletti S & Dell'Orfano H.  Medication adherence in cardiovascular disease. 2010. 
Circulation. 121:1455-1458 
vii Burnier M et al.  Measuring, analyzing and managing drug adherence in resistant 
hypertension. 2013. Hypertension. 62: 218-225 
viii Daugherty SL et al. Incidence and prognosis of resistant hypertension in hypertensive 
patients. 2012. Circulation. 125: 1635-1642 
ix Schmieder RE et al. Updated ESH position paper on interventional therapy of resistant 
hypertension. 2013. Eurointervention. Suppl R: R58-R66. Review 
x Grassi G & Mancia G. New therapeutic approached for resistant hypertension. 2012. J 
Nephrol. 25: 276-81. Review 
xi Joyner M., et al. The sympathetic nervous system and blood pressure in humans: 
individualized patterns of regulation and their implications. 2010. Hypertension. 56: 10-16 
xii Guynet PG. The sympathetic control of blood pressure. 2006. Nat Rev Neurosci 7: 335-346. 
Review 
xiii DiBona GF et al. Reflex effects on renal nerve activity characteristics in spontaneously 
hypertensive rats. 1997. Hypertension. 30:1089-96. 
xiv Camprese VM & Kogasov E. Renal afferent denervation prevents hypertension in rats with 
chronic renal failure. 1995. Hypertension. 25:78-82 
xv Smithwick RH & Thomson JE. Splanchnicetomy for essential hypertension; results in 1,266 
cases. 1953. J Am Med Assoc. 152: 1501-1504 

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xvi Evelyn KA et al. Effect of thoracolumbar sympathectomy on the clinical course of primary 
(essential) hypertension. A ten-year study of 100 sympathectomized patients compared with 
individually matched, symptomatically treated control subjects. 1960. Am J Med. 28:188-221 
xvii Krum H et al. Catheter-based renal sympathetic denervation for resistant hypertension: a 
multicentre safety and proof-of-principle cohort study. 2009. Lancet. 373:1275-1281 
xviii Esler M et al. Renal sympathetic denervation in patients with treatment-resistant 
hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. 2010. Lancet. 
376:1903-1909 
xix Esler M et al. Renal sympathetic denervation for treatment of drug-resistant hypertension: 
one-year results from the Symplicity HTN-2 randomized, controlled trial. 2012. Circulation. 
126:2976-2982. 
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