A Study of the ReCor Medical Paradise System in Clinical Hypertension

Study Overview
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Brief Summary
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RADIANCE-HTN is a randomized, double-blind, sham controlled, 2-cohort study (TRIO and SOLO) designed to demonstrate efficacy and document the safety of the Paradise Renal Denervation System in two distinct populations of hypertensive subjects.

Detailed Description
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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. Prior to randomization, subjects will be hypertensive in the absence of hypertension medication (SOLO) or despite the presence of a stabilized, single pill, triple, fixed dose antihypertensive medication regimen (TRIO).

Official Title
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The RADIANCE-HTN Study. A Study of the ReCor Medical Paradise System in Clinical Hypertension

Conditions
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Hypertension, Vascular Diseases

Intervention / Treatment
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* Device: The Paradise® Renal Denervation Ultrasound System
* Device: Sham Procedure


Participation Criteria
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Eligibility Criteria
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TRIO and SOLO Inclusion Criteria: Appropriately signed and dated informed consent Age ≥18 and ≤75 years at time of consent Documented history of essential hypertension SOLO Cohort only: Either an average seated office BP < 180/110 mmHg at screening visit while on a stable regimen of 1 or 2 antihypertensive medications for at least 4 weeks prior to consent or an average seated office BP ≥ 140/90 mmHg <180/110 mmHg despite lifestyle measures on no antihypertensive medications TRIO Cohort only: Average seated office BP ≥ 140/90 mmHg at screening visit 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 and < 170/105 mmHg after 4-week washout/run-in period (SOLO cohort) or after 4-week stabilization period (TRIO cohort) 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 Solo Exclusion Criteria: Renal artery anatomy on either side, ineligible for treatment including: Main renal artery diameter < 4 mm and > 8 mm Main renal artery length < 25 mm A single functioning kidney Presence of abnormal kidney (or secreting adrenal) tumors Renal artery with aneurysm Pre-existing renal stent or history of renal artery angioplasty Prior renal denervation procedure Fibromuscular disease of the renal arteries Presence of renal artery stenosis of any origin ≥ 30% 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 Chrohn'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 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) TRIO Exclusion Criteria Renal artery anatomy on either side, ineligible for treatment including: Main renal artery diameter < 3.5 mm and > 8 mm Main renal artery length < 20 mm A single functioning kidney Presence of abnormal kidney tumors Renal artery with aneurysm Pre-existing renal stent or history of renal artery angioplasty Pre-existing aortic stent or history of aortic aneurysm Prior renal denervation procedure Fibromuscular disease of the renal arteries Presence of renal artery stenosis of any origin ≥ 30% Accessory arteries with diameter ≥2 mm <3.5 mm and > 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 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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ultrasound Renal Denervation<br>Subjects in the TRIO or SOLO cohorts that are randomized to treatment, will receive renal denervation following a renal angiogram | Device: The Paradise® Renal Denervation Ultrasound System<br>* Randomization will occur following the diagnostic renal angiogram. Blinded patients randomized to treatment will receive the renal denervation procedure using the Paradise System to deliver ultrasound energy to thermally ablate and disrupt the renal sympathetic nerves while sparing the renal arterial wall.<br>* Other names: renal denervation;|
| Sham Comparator: Sham Procedure<br>For subjects in TRIO or SOLO cohorts that randomize to the sham procedure, the diagnostic renal angiogram intervention will be considered the sham procedure. | Device: Sham Procedure<br>* Randomization will occur following the diagnostic renal angiogram. For blinded patients randomized to control, the diagnostic renal angiogram will be considered the sham procedure.<br>* Other names: renal angiogram;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean reduction in average daytime ambulatory systolic BP |  | from baseline to 2 months post procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in average 24-hr/night-time ambulatory systolic BP |  | from baseline to 2 months post procedure | 
| Reduction in average daytime/24-hr/night-time diastolic BP |  | from baseline to 2 months post procedure | 
| All-cause mortality |  | from baseline to 36 months post-procedure | 
| Hypertensive or hypotensive emergency resulting in hospitalization |  | up to 36 months | 
| Hospitalization for heart failure |  | from baseline to 36 months post-procedure | 
| Stroke, transient ischemic attack, cerebrovascular accident |  | from baseline to 36 months post-procedure | 
| Acute myocardial infarction |  | from baseline to 36 months post-procedure | 
| End stage renal disease |  | from baseline to 36 months post-procedure | 
| Renal artery or vascular complications requiring intervention |  | from baseline to 36 months post-procedure | 
| Significant embolic events resulting in end organ damage |  | from baseline to 1 month and 36 months post-procedure | 
| Procedure related pain lasting > 2 days |  | from baseline to 1 month and 36 months post-procedure | 
| Acute renal injury |  | from baseline to 1 month and 36 months post-procedure | 
| 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 study defined renal CTA/MRA at 12 months | from baseline to 6, 12, 24 and 36 months post-procedure | 
| Major access site complications |  | from baseline to 1 month and 36 months post-procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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denervation, resistant hypertension, essential hypertension