REnal Sympathetic dEnervaTion as an a Adjunct to Catheter-based VT Ablation
Phase: NA
Conditions: Ventricular Tachycardia
Sponsor: Vivek Reddy

REnal Sympathetic dEnervaTion as an adjunct to catheter-based VT Ablation
RESET-VT
Dr. Vivek Reddy
NCT01858194
Document Date: November 2012

Renal VT Version 1.3 November 2012 
 
 
1 
 
 
 
 
 
 
 
 
 
REnal Sympathetic dEnervaTion as an adjunct to 
catheter-based VT Ablation 
 
RESET-VT 
VERSION 1.3 
NOVEMBER 2012 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Renal VT Version 1.3 November 2012 
 
 
2 
 
 
Table of Contents: 
 
 
 
 
1. CONTACT INFORMATION 
1.1. STUDY SITES & INVESTIGATORS 
 
2. STUDY OBJECTIVE 
 
3. INTRODUCTION, RATIONALE  
 
4. SCHEDULE OF TREATMENTS AND TESTS 
 
5. ENDPOINTS 
5.1. PRIMARY CLINICAL ENDPOINT 
5.2. SECONDARY CLINICAL ENDPOINTS 
 
6. STUDY SUBJECTS 
6.1. INCLUSION CRITERIA 
6.2. EXCLUSION CRITERIA 
 
7. SAMPLE SIZE CALCULATION 
 
8. PATIENT ENROLLMENT AND WITHDRAWAL 
 
9. STUDY PROCEDURES 
9.1. PRE- AND ABLATION PROCEDURE 
9.1.1. PRE-PROCEDURE 
9.1.2. PRE-PROCEDURE MEDICATION MANAGEMENT 
9.1.3. ABLATION PROCEDURAL DETAILS 
9.1.4. RENAL SYMPATHETIC ABLATION DETAILS 
9.2. POST-PROCEDURE 
9.2.1. POST-PROCEDURE FOLLOW-UP 
9.2.2. POST-PROCEDURE MEDICATION MANAGEMENT 
9.2.3. ICD PROGRAMMING 
9.3. SAFETY 
9.4. RISKS 
10. ETHICAL AND REGULATORY CONSIDERATIONS 
11. STUDY MANAGEMENT 
12. DATA HANDLING 
 
REFERENCES 
 
 
 
 
 

Renal VT Version 1.3 November 2012 
 
 
3 
 
 
PROTOCOL SUMMARY 
Title: 
RESET-VT 
 
Objective: 
The goal of this trial is to test the impact of catheter-based renal 
sympathetic denervation (RSDN) as an adjunctive treatment for 
patients with either ischemic or non-ischemic cardiomyopathy 
undergoing catheter ablation of ventricular tachycardia (VT). 
The proposed study is a prospective, multicenter, randomized 
control trial. Patients undergoing VT ablation will be 
randomized to either VT ablation alone or VT ablation + RSDN.  
 
 
Design: 
This study is a prospective, multicenter, single-blinded, 
randomized (1:1) control trial evaluating the effectiveness of 
RSDN in the prevention of recurrent VT in patients with 
ischemic or non-ischemic ventricular dysfunction who are 
undergoing catheter ablation for VT.  These patients will be 
randomized to ablation alone or ablation + RSDN. Subjects will 
only be eligible for this study if they are ≥ 18 years of age and 
have a history of structural heart disease (post-MI, dilated 
cardiomyopathy, sarcoid myopathy, hypertrophic 
cardiomyopathy, etc.), have an existing ICD and are planned for 
catheter-based VT ablation. In addition, eligible patients will 
have accessible renal vasculature (as determined by renal 
angiography). 
 
 
The patient will be blinded to the results of randomization. Once 
randomized, study group subjects will undergo a strategy of 
catheter-based renal sympathetic denervation + VT ablation. 
Follow-up will be conducted in regular intervals over a 24-
month period. 
 
 
 
 
Enrollment: 
 
 
Total: 202 subjects 
 
Pilot Phase: 20 subjects (~10 control group, ~10 study group) 
 
Clinical Sites: 
 Mount Sinai School of Medicine (PILOT) 
 Homolka Hospital, Prague, Czech Republic (PILOT) 
 Other Sites TBD (total up to 25 sites) 
 
Time Course: 
Initial enrollment:  December 2012 

Renal VT Version 1.3 November 2012 
 
 
4 
 
Last enrollment: July 2013 (Pilot) 
Last 24-month follow-up: July 2015 (Pilot) 
 
Subject Description: 
 
 
 
 
 
 
 
Study Group: 
 
 
 
Control Group: 
 
 
 
 
Eligible subjects include those ≥ 18 years of age with a history 
of structural heart disease (post-MI, dilated cardiomyopathy, 
sarcoid myopathy, hypertrophic cardiomyopathy, etc.), have an 
existing ICD and are planned for catheter-based VT ablation. In 
addition, eligible patients will have accessible renal vasculature 
(as determined by renal angiography). 
 
In addition to VT ablation, the subjects in this group will 
undergo catheter-based renal sympathetic denervation.  
 
Subjects in the control group will undergo a standard procedure 
for catheter-based VT ablation.  
Primary Endpoint: 
1. Time to first event requiring appropriate ICD therapy for 
ventricular arrhythmia or Incessant VT (VT occurring 
below the ICD rate cut-off) 
Secondary Endpoints: 
 
1. Appropriate ICD therapy for ventricular arrhythmia 
2. Appropriate ICD Shocks ventricular arrhythmia 
3. Inappropriate ICD therapy 
4. All ICD therapy (Appropriate + Inappropriate) 
5. A composite of Mortality, ICD storm, and Incessant VT 
(VT occurring below the ICD rate cut-off) 
6. Number of Hospitalizations for Cardiovascular Causes. 
7. Total VT burden (Number of episodes). 
8. All-Cause Mortality. 
9. The occurrence of ICD storm, defined as ≥3 appropriate 
shock therapies within 24 hours. 
10. Differences in blood hormone measurements (including 
norepinephrine, aldosterone, renin, and BNP). 
11. Differences in BUN/creatinine measurements. 
12. Differences in cardiac parameters, including LV size 
(septal and free wall thickness) and mitral inflow (E&A 
velocity), 
as 
measured 
by 
trans-thoracic 
echocardiography. 
13. Procedure related adverse events including, but not 
limited to hematomas, pseudoanuerysms, renal artery 
stenosis, renal impairment, thromboembolic events, 
stroke, pericardial bleeding including tamponade and 
myocardial infarction 
14. Change in blood pressure 

Renal VT Version 1.3 November 2012 
 
 
5 
 
15. Development of orthostatic hypotension 
16. Other individual complication rates including, but not 
limited to MI and death.  
17. 30-day Major Complication Rate defined as death, 
stroke, MI or any other serious adverse events related to 
the treatment or procedure within the first 30 days or 
through hospital discharge (whichever is longer); 
18. Procedure time 
 
Primary Analytical 
Analysis: 
Intent to treat analysis 
Secondary Analytical 
Analysis: 
Per protocol analysis 
Principal Investigator: 
Vivek Y. Reddy, M.D. 
Mount Sinai School of Medicine 
One Gustave L Levy Place, Box 1030 
New York, NY 10029, USA 
 
Site, Monitoring, and Data 
Management Center 
Electrophysiology Clinical Research Group 
Mount Sinai School of Medicine 
One Gustave L Levy Place, Box 1030 
New York, NY 10029, USA 
 
 
 
Data Safety and Monitoring 
Board: 
TBD  
 
 
 

Renal VT Version 1.3 November 2012 
 
 
6 
 
 
1   CONTACT INFORMATION 
 
 
PRINCIPAL INVESTIGATOR: 
 
 VIVEK Y. REDDY, MD 
 
 MOUNT SINAI SCHOOL OF MEDICINE 
 
 HELMSLEY TRUST ELECTROPHYSIOLOGY CENTER 
 
 ONE GUSTAVE L. LEVY PLACE, BOX 1030 
 
 NEW YORK, NY 10029 
 
 TEL: (212) 241-7114 
 
 FAX: (646) 537-9691 
 
 EMAIL: VIVEK.REDDY@MOUNTSINAI.ORG 
 
1.1 STUDY SITES & INVESTIGATORS  
 
Site 
Principal Investigator 
1. Mount Sinai School of Medicine 
Vivek Y. Reddy, MD 
2. Homolka Hospital, Prague, Czech Republic Petr Neuzil, MD 
3. TBD 
 
 
 
2 
STUDY  OBJECTIVE 
The goal of this trial is to test the impact of catheter-based renal sympathetic denervation 
(RSDN) as an adjunctive treatment for patients with either ischemic or non-ischemic 
cardiomyopathy undergoing catheter ablation of ventricular tachycardia (VT). The proposed 
study is a prospective, single-blind, multicenter, randomized control trial. Patients undergoing 
VT ablation will be randomized to either ablation alone or ablation + RSDN.  
 
3 
INTRODUCTION, RATIONALE 
 
Sudden cardiac death (SCD), defined as an unexpected death from a cardiac cause occurring 
within ≤ 1 hour of the onset of symptoms, accounts for 300,000 to 400,000 deaths in the United 
States annually, or 5.6% of annual mortality.1-3 SCD is most commonly caused by ventricular 
tachy-arrhythmias, including ventricular tachycardia (VT).  Several therapies exist for the 
prevention of VT, including implantable cardioverter-defibrillator therapy (ICD), anti-arrhythmic 
drug therapy (AAD), and the use of catheter based ablation.  
 
Current guidelines recommend the use of implantable cardioverter-defibrillator (ICD) as therapy 
to prevent SCD in patients who have survived a prior cardiac arrest due to unstable VT or who 
have had a previous episode of spontaneous sustained VT.4 Several trials have demonstrated the 
efficacy of ICD therapy in preventing SCD.5,6  The MADIT II trial, a randomized trial of patients 
with prior myocardial infarction and left ventricular ejection fraction ≤30%, demonstrated a 31% 
reduction in the relative risk of death in the defibrillator group. 6 However, ICD therapy does not 
prevent VT, and a significant proportion of patients may still experience appropriate shocks. In 
the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial, 60% of patients had ≥1 
appropriate ICD therapy for VT/VF during follow-up (31±13 months), and the first arrhythmia 
resulting in a shock during follow up was frequently identified as VT (63%). Unfortunately, 
these ICD shocks are associated with both a significant reduction in quality of life and increased 

Renal VT Version 1.3 November 2012 
 
 
7 
 
mortality. In a study examining quality of life in patients who had received ICD shocks, at 5.5 
years post ICD implantation 19% of patients demonstrated signs of post-traumatic stress 
disorder.7 In the MADIT II trial, patients who experienced VT/VF had an increased risk of death, 
with a hazard ratio of 2.5.6  Thus, while ICDs have a clear overall mortality benefit in patients 
with a reduced ejection fraction, the ICD shocks themselves clearly reduce the quality-of-life of 
these patients and may have a negative impact on longevity.  
 
Antiarrhythmic drugs (AADs) are another therapy available for the prevention of VT, but 
unfortunately they have little effect on ventricular arrhythmia recurrence, and may increase 
mortality when used in high-risk patients. In the OPTIC trial, 412 patients who had an ICD 
implanted within 21 days for inducible or spontaneously occurring VT/VF were randomized to 
either amiodarone plus beta-blocker, sotalol alone, or beta-blocker alone. Although patients in 
the amiodarone plus beta blocker group were less likely to receive shocks (HR, 0.27; 95% CI, 
0.14-0.52; P<.001), shocks still occurred in 10.3% of these patients. In addition, serious adverse 
effects associated with amiodarone resulted in study drug discontinuation in 18.2% of patients at 
1 year.8 
 
More recently, catheter ablation has emerged as a new option for the primary prevention of ICD 
shocks. Current guidelines recommend catheter ablation for symptomatic sustained 
monomorphic VT, including VT terminated by an ICD, that recurs despite AAD therapy or when 
AADs are not tolerated. In addition, ablation is indicated for control of VT storm refractory to 
drug therapy when there is a suspected trigger than can be targeted for ablation.9 The Substrate 
Mapping and Ablation in Sinus Rhythm to Halt Ventricular Tachycardia Study (SMASH-VT) 
randomized patients with a history of myocardial infarction who underwent defibrillator 
implantation for spontaneous VT or VF, to either defibrillator implantation alone or defibrillator 
implantation plus substrate-based catheter ablation. In patients who underwent defibrillator 
implantation alone 33% received ICD therapies (anti-tachycardia pacing or shocks), compared to 
12% in patients who received defibrillator implantation plus substrate-based catheter ablation 
(Hazard ratio in the ablation group, 0.35; 95% confidence interval, 0.15 to 0.78, P=0.007).10  
Similar results were seen in another multicenter randomized trial of similar design, VTACH.  
Despite the efficacy of VT ablation in these trials, there remain a significant number of patients 
how have recurrent arrhythmic events after catheter ablation procedures. This is particularly true 
in patients who present with ventricular arrhythmias refractory to anti-arrhythmic drugs and 
device therapies.  
 
Thus, anti-arrhythmic drugs and catheter ablation each have limitations as sole therapies in 
patients at risk for recurrent ICD shocks. One adjunctive strategy under investigation is renal 
sympathetic denervation (RSDN). Recently, RSDN has been developed as a therapy to treat 
hypertension in patients resistant to anti-hypertensive drug therapy. In the Catheter-Based Renal 
Sympathetic Denervation for Resistant Hypertension: a multicentre safety and proof-of-principle 
cohort study, 45 patients with a mean office blood pressure of 177/101 mm Hg (SD 20/15), 
(mean 4.7 antihypertensive medications)  underwent renal sympathetic denervation with  
radiofrequency based catheter ablation. After the procedure, these patients experienced a mean 
decrease in office blood pressure of -27/-17 mm Hg at 12 months, as well as a 47% reduction in 
renal noradrenaline spillover.11 In the Renal Sympathetic Denervation in Patients with 
Treatment-Resistant Hypertension (Symplicity HTN-2) Trial, a multi-center prospective trial that 

Renal VT Version 1.3 November 2012 
 
 
8 
 
randomized 106 patients to RSDN or medical management, at 6 months, 84% of patients who 
underwent renal denervation had a reduction in systolic blood pressure of 10 mm  Hg or more, 
compared with 35% of controls (p<0·0001). 
 
RSDN is thought to decrease blood pressure by a number of mechanisms including its ability to 
favorably affect whole body norepinephrine spillover and decrease central sympathetic tone. 
Indeed, RSDN has been shown to reduce whole body norepinephrine spillover by 42%, and 
efferent muscle sympathetic nerve activity by 66%.12 Interestingly, increased catecholamine and 
sympathetic activity are both important factors in the development of ventricular arrhythmias.13-
18 In addition, chronic hypertension is believed to mediate pathogenesis and progression of 
cardiac arrhythmias via its remodeling effects on cardiac anatomy through the renin-angiotensin-
aldosterone system.19    
 
Logically, RSDN may be an effective therapy in the prevention of SCD from VT.  Interestingly, 
there is at least one case report examining the impact of RSDN for the treatment of recurrent 
appropriate ICD shocks; two patients with ICDs for scar-related VT and CHF underwent RSDN 
for therapy resistant electrical storm. 20 One patient with hypertrophic cardiomyopathy had 
recurrent monomorphic VT despite multiple endocardial and epicardial ablations, while the 
second patient with dilated non-ischemic cardiomyopathy suffered from recurrent polymorphic 
VT, and had declined catheter ablation therapy.  After undergoing RSDN, both patients 
experienced significantly less episodes of VT requiring ATP or shocks. Importantly, despite 
normal to low blood pressure at baseline, both patients maintained a stable blood pressure at 6 
months of follow up post procedure. 
 
Rationale for RESET-VT: 
 
Despite significant advances in the management of ventricular arrhythmias through the use of 
ICD therapy, AADs, and catheter-based ablation strategies, considerable challenges remain. The 
optimal method for the prevention of recurrent VT following catheter ablation remains unclear. 
RSDN may be an effective tool for preventing ventricular arrhythmias, and associated ICD 
therapies, by reducing central sympathetic tone, catecholamine levels, and the renin-angiotensin-
aldosterone system and promoting ventricular remodelling. Although RSDN has been shown to 
reduce the recurrence of VT in a case report of 2 patients suffering from electrical storm, to date 
no large prospective randomized study has evaluated the impact of RSDN in the prevention of 
recurrent VT in patients following catheter ablation of VT with ischemic or non-ischemic 
ventricular dysfunction. This study will specifically evaluate the safety and efficacy of 
adjunctive RSDN in the prevention of ICD therapy in patients with ischemic or non-ischemic 
ventricular dysfunction who are to receive a catheter-based VT ablation.  

Renal VT Version 1.3 November 2012 
 
 
9 
 
 
4.  Schedule of Treatment and Tests: 
 
TABLE 1: SCHEDULE OF TREATMENTS AND TESTS: 
 
Baseline 
 Procedure* 
Discharge 
1 month 
6,12,18 & 24 
months 
 
Type of visit 
 
 
Office 
 
Hospital 
 
Office 
Office or 
Transtelephonic 
 
Informed Consent 
 
 
X 
 
 
 
 
 
Brief History & Physical 
 
 
X 
 
 
 
 
X 
 
Blood Laboratory Testing: 
CBC, Electrolytes, 
BUN/Creatinine, BNP 
X 
 
 
 
X 
(12, 24m) 
NIH Stroke Scale 
X 
 
X 
 
 
Blood for Renal Hormones 
(OPTIONAL) 
X 
 
 
 
X  
(12m) 
 
TTE 
 
 
X 
 
 
 
 
X  
(12 m) 
 
Renal Angiography 
 
 
 
 
X 
 
 
 
 
Ultrasound or MR/CT 
Angiography  
 
 
 
 
X 
(6 m) 
 
Randomization 
 
 
 
X 
 
 
 
Renal Sympathetic 
Denervation 
 
 
X 
 
 
 
 
 
ICD Interrogation/remote 
transmission 
 
 
X 
 
 
 
 
 
X 
X 
 
EKG 
 
 
X 
 
 
 
 
 
 
X 
(12m) 
 
Office BP Measurements 
(including orthostatic BPs) 
 
 
X 
 
 
 
 
X 
X 
(12m) 
 
Medications 
 
 
X 
 
 
 
X 
 
X 
X 
 
Adverse Events 
 
 
X 
 
X 
 
X 
X 

Renal VT Version 1.3 November 2012 
 
 
10 
 
 
 
5.  Endpoints: 
 
 
5.1: Primary Endpoint: 
 
The following primary endpoint will be assessed:  Time to first event requiring appropriate ICD 
therapy or Incessant VT (VT occurring below the ICD rate cut-off); this will be assessed in the 
on-treatment patient cohort. 
 
5.2: Secondary Endpoints:  
 
The following secondary endpoints will be assessed: 
 
1) Appropriate ICD therapy for ventricular arrhythmia assessed in the full intention-to-treat 
patient cohort 
2) Appropriate ICD Shocks for ventricular arrhythmia 
3) Inappropriate ICD therapy 
4) All ICD therapy (Appropriate + Inappropriate) 
5) A composite of Mortality, ICD storm, and Incessant VT (VT occurring below the ICD 
rate cut-off) 
6) Number of Hospitalizations for Cardiovascular Causes. 
7) Total VT burden (Number of episodes). 
8) All-Cause Mortality. 
9) The occurrence of ICD storm, defined as ≥3 appropriate shock therapies within 24 hours. 
10) Differences in blood hormone measurements (including norepinephrine, aldosterone, 
renin, and BNP). 
11) Differences in BUN/creatinine measurements. 
12) Differences in cardiac parameters, including LV size (septal and free wall thickness) and 
mitral inflow (E&A velocity), as measured by trans-thoracic echocardiography. 
13) Procedure related adverse events including, but not limited to hematomas, 
pseudoanuerysms, renal artery stenosis, renal impairment, thromboembolic events, 
stroke, pericardial bleeding including tamponade and myocardial infarction. 
14) Development of orthostatic hypotension 
15) Changes in blood pressure 
16) Other individual complication rates including, but not limited to MI and death.  
17) 30-day Major Complication Rate defined as death, stroke, MI or any other serious 
adverse events related to the treatment or procedure within the first 30 days or through 
hospital discharge (whichever is longer); 
18) Procedure time 
 
6.  STUDY SUBJECTS 
 
6.1 INCLUSION CRITERIA 
 
State inclusion criteria for enrollment in study:  

Renal VT Version 1.3 November 2012 
 
 
11 
 
 
1. 
≥ 18 years of age 
2. 
Structural heart disease (post-MI, dilated cardiomyopathy, sarcoid myopathy, 
hypertrophic cardiomyopathy, chagas-related cardiomyopathy, etc.) 
3. 
Planned for catheter-based ablation of VT 
4. 
All patients will have an existing ICD  
5. 
Accessibility of renal vasculature (determined by renal angiography) 
6. 
Ability to understand the requirements of the study 
7. 
Willingness to adhere to study restrictions and comply with all post-         
procedural follow-up requirements 
 
 6.2 Exclusion Criteria  
 
Clinical Exclusion Criteria:  
1) MI or CVA within 30 days 
2) Coronary Artery Bypass Graft (CABG) within 30 days of this procedure 
3) Known renovascular abnormalities that would preclude RSDN (eg, renal artery 
stenosis) 
4) GFR <30 ml/min (unless receiving dialysis) 
5) Life expectancy <1 year for any medical condition 
6) Any condition resulting in a contraindication to anticoagulation (e.g. GI bleeding) 
7) Inability to give informed consent 
8) Known pregnancy or positive -HCG within 7 days of procedure. 
 
7. Sample Size Calculation: 
 
We generated our sample size using the following key assumptions: 
1. In patients receiving catheter ablation for VT alone, the estimated success rate 
(absence of ICD therapy) at 2 years is 65% 
2. In patients receiving RSDN in addition to VT ablation, we expect a 30% 
improvement such that the estimated 2 year success rate is 85% 
 
The power analysis revealed that a 30% improvement in therapy with RSDN would be detected 
with 83 patients per arm (80% power, 2-sided alpha error of 0.05). This would require an 
enrollment of a total of 168 patients, with follow-up of 2 years. We expect an ~10% loss to 
follow-up.  Accordingly, we will plan to enroll an additional ~10% of patients so as to have 
sufficient number of randomized patients: this would require 184 patients. In addition, we expect 
10% of patients will have renal vasculature inappropriate for the RSDN procedure (these are 
patients that will be consented pre-procedure, but will screen out after renal angiography during 
the VT ablation procedure).  Accordingly, we will ultimately plan to include a total of 202 
patients: ~18 patients would screen out after renal angiography, and there would remain a total of 
92 patients randomized to each arm. 
 
This study is divided into two phases: a PILOT phase (to include 20 patients) followed by the 
remaining 182 patients to a total of 202 patients. The PILOT phase will be conducted at 2 sites: 
Homolka Hospital (Prague, Czech Republic) and Mount Sinai Medical Center. An interim safety 

Renal VT Version 1.3 November 2012 
 
 
12 
 
analysis for the primary endpoint will be conducted when all patients in the PILOT phase (20 
subjects) have completed the 1-month follow up visit. 
 
 
8. Patient Enrollment and withdrawal: 
 
This will be a multicenter trial.  Patients meeting the study inclusion criteria will be identified in 
the outpatient or inpatient setting by one of the study sites’ primary or co-investigators.   
 
The study will typically be described (including the risks and benefits) during the initial clinic or 
hospital visit.  Consent will typically be obtained at the time of the initial assessment if it is clear 
that the patient truly understands the nature of the study.  Alternatively, the patient will be 
allowed to take a copy of the consent form home to contemplate whether they would like to be 
enrolled in the study.  A sample consent form can be found in Appendix 1.  Only patients who 
voluntarily provide consent will be included in this study.  Consent will be obtained prior to 
undergoing the ablation procedure. Patients will be able to withdraw from the study at any point 
without compromising their medical care.   
 
Consent must be obtained before the VT ablation procedure.

5HQDO979HUVLRQ1RYHPEHU



 3UH3URFHGXUHDQG$EODWLRQ6WXG\'HVLJQ)ORZ&KDUW
6FUHHQLQJ,QFOXVLRQ&OLQLFDO([FOXVLRQ&ULWHULD
$VVHVVPHQW*HQHUDODQGDUUK\WKPLDKLVWRU\HFKREORRGODERUDWRU\
WHVWLQJRIILFH%3PHDVXUHPHQW%DVHOLQH77(EORRGZRUN%DVHOLQH
,&'LQWHUURJDWLRQDQG1,+VWURNHVFDOH
5DQGRPL]DWLRQ
3ODFHER$UP
1RIXUWKHUWKHUDS\
)ROORZ8S
¾ )ROORZXSRFFXUVDW
DQGPRQWKV,&'LQWHUURJDWLRQ
DWHDFKYLVLW
¾ %ORRGODERUDWRU\WHVWLQJDWDQG
PRQWKV
¾ (.*DWPRQWKV
¾ (FKRDWPRQWKV
¾ 5HQDOXOWUDVRXQGRU&705
$QJLRJUDSK\DWPRQWKV
5DQGRPL]DWLRQZLOOEHSHUIRUPHGDIWHULQWUDSURFHGXUDOUHQDODQJLRJUDSK\WRHQVXUH
WKDWWKHYDVFXODWXUHLVDPHQDEOHWRFDWKHWHUEDVHGUHQDOV\PSDWKHWLFGHQHUYDWLRQ
97$EODWLRQ
$EODWLRQ$UP
&DWKHWHUEDVHGUHQDO
V\PSDWKHWLFGHQHUYDWLRQ
5HQDO$QJLRJUDSK\
3DWLHQWVZLWKXQVXLWDEOHUHQDODUWHULHVH[FOXGHGDV
VFUHHQ IDLOXUH

Renal VT Version 1.3 November 2012 
 
 
14 
 
 
PRE- AND ABLATION PROCEDURE 
 
9.1.1 
PRE-PROCEDURE  
The following tests and procedures will occur before the ablation: 
 
 
Recording of patient medical history (including details of  VT both clinical/ICD) 
 
Recording medication history (including all AAD ever used, duration of use) 
 
Obtain β-HCG in females of child bearing age the morning of the procedure as per usual clinical 
practice 
 
Baseline assessment of arrhythmia burden and type: Office/inpatient records, ICD interrogation 
report 
 
Baseline NIH stroke scale 
 
If performed for any reason, collect any pre-procedural imaging: MRI/CT and Renal Ultrasounds 
within 6 months of procedure   
 
Baseline laboratory, including complete blood count, standard electrolyte panel, renal function, 
and brain natriuretic peptide levels. 
 
Baseline Transthoracic Echocardiogram 
 
Baseline blood pressure. Proper blood pressure measurement technique is essential: i) patient 
should sit quietly in a chair with his/her back supported for 5 minutes before taking the 
measurement; ii) use of the correct cuff size with the air bladder encircling at least 80% of the 
arm (the adult large cuff for the majority of patients); iii) support the arm at heart level during the 
cuff measurement; iv) a minimum of 2 readings should be taken at intervals of at least 1 minute 
and the average of those readings should be taken to represent the patient’s blood pressure; v) the 
blood pressure should be measured 
 
Consent must be obtained before the VT ablation procedure. 
 
Randomization into one of two groups will be performed by opening the Randomization envelope 
after Renal Angiography. 
Study/Experimental Group:  These subjects will undergo catheter-based sympathetic 
renal denervation.  
Placebo Control Group: These subjects will receive no further intervention.. 
 
9.1.2 
PRE-PROCEDURE MEDICATION MANAGEMENT 
After the ablation procedure, patients should receive either an antiplatelet agent (aspirin, 
clopidogrel, etc) or anticoagulant (warfarin, dabigatran, etc) for at least 1 week.  Further decisions 
regarding the peri-procedural management of other cardiovascular (including anti-coagulant and 
anti-thrombotic agents) and non-cardiovascular medications should be as per clinical practice – 
but every effort should be made to maximize beta-blocker therapy, ACEI/ARB, and 
spironolactone therapy as per the guidelines.    
 
9.1.3 
VT ABLATION PROCEDURAL DETAILS  
 
Patients will be brought to the electrophysiology laboratory in a fasting state 
 
General anesthesia/conscious sedation will be used according to operator preference 
 
Patients will undergo electrophysiology study and VT ablation as per standard practice 
 
Therapeutic anticoagulation will be administered with intravenous heparing with a target 
ACT of 300 seconds or greater.  
 
9.1.4 
RENAL SYMPATHETIC ABLATION PROCEDURAL DETAILS 
 
In patients randomized to receive RSDN, the procedure will be performed after the VT ablation 
on therapeutic anticoagulation with intravenous heparin.  

Renal VT Version 1.3 November 2012 
 
 
15 
 
 
Abdominal aortography will be performed to assess the renal arteries for the suitability of 
catheter-based renal denervation in all patients. For those patients in whom the angiogram 
demonstrates that the renal anatomy is inappropriate for the RSDN procedure (small renal 
arteries, extensive atherosclerosis, renal stenosis, etc), the patient will be excluded from the study 
as a screen failure. The patient’s baseline information will be collected but no further follow-up 
required (beyond assessing for any adverse events related to the procedure).  If the renal arteries 
are deemed suitable for RSDN, the patient will then undergo randomization. 
 
Randomization will be done by permuted-block randomization centrally and will be stratified by 
site. Allocation concealment shall be maintained at all sites by the use of a web-based central 
randomization scheme. The operating physician controlling the delivery of ablative energy will 
be aware of the outcome.  This approach has been selected to minimize (1) study bias and (2) 
placebo effect. The randomization schema will be blocked by size for each site.   
 
After confirmation of eligibility, an irrigated radiofrequency ablation catheter will be introduced 
sequentially into each renal artery. 
 
The ablation catheter is placed within a long vascular sheath and advanced into the renal artery.  
The sheath is advanced over the catheter to engage the renal artery ostium and allow for contrast 
injection and visualization of the vessel during catheter manipulation.   
 
After completion of the measurement, no more than six radiofrequency ablation lesions separated 
both longitudinally and rotationally (a ―spiral pattern‖, see figure) will be placed per renal artery.  
The power will be started at 10 W and titrated to a maximum 20 W, as deemed appropriate by the 
impedance drop (goal 10% drop).  Each lesion should be between 30-120 seconds in duration (no 
more than 120 seconds per lesion). 
 
 
 
 
 POST-PROCEDURE 
 
9.2.1 
POST-PROCEDURE FOLLOW UP 
 
 
All patients will be monitored to verify vascular hemostasis prior to discharge from the 
hospital.   
 
All patients will receive either oral aspirin (81-325 mg QD) or clopidogrel (75 mg QD) or 
warfarin or dabigatran or rivaroxiban for at least 1 week upon discharge. 
 
Medication and adverse event review will be performed prior to discharge.  
 
Complications including vascular, stroke, heart failure etc, and presence of ventricular 
arrhythmias will be documented. 
 
NIH stroke scale will be repeat post-procedure 
 
ICD programming:  (see below section 9.2.3) 

Renal VT Version 1.3 November 2012 
 
 
16 
 
 
The total number of episodes of VT, ATP, and Shocks will be documented at all visits. 
 
The follow-up includes: 
o 1 Months 
 
History and Physical 
 
ICD interrogation (may be trans-telephonic) 
 
Office BP measurements (x2) including orthostatics 
 
Review of Medications and Adverse events 
o 6 Months 
 
 
ICD interrogation (may be trans-telephonic) 
 
Review of Medications and Adverse Events 
 
Repeat Renal Ultrasound or MR/CT Angiography 
o 12 Months:  
 
ICD interrogation (may be trans-telephonic) 
 
EKG 
 
Office BP measurements (x2) including orthostatics 
 
Lab tests (CBC, Electrolytes, BUN/Cr) 
 
Blood for Renal Hormones (OPTIONAL) 
 
BNP Level. 
 
Review of Medications and Adverse Events 
 
Repeat TTE 
o 18 Months: 
 
ICD interrogation (may be trans-telephonic) 
 
Review of Medications and Adverse Events 
o 24 Months: 
 
ICD interrogation (may be trans-telephonic) 
 
Lab tests (CBC, Electrolytes, BUN/Cr) 
 
BNP Level 
 
Review of Medications and Adverse Events 
 
9.2.2 
POST-PROCEDURE MEDICATION MANAGEMENT 
 
 
 
Standard cardiovascular medications are left up to the discretion of the investigator – but 
BBLs, ACEI, ARBs and aldosterone antagonist use is recommended as per standard 
guidelines. 
 
Therapeutic anticoagulation (example Warfarin or equivalent agent) beyond the requisite 1 
week post-procedure timepoint is at the discretion of the patient’s physician.  
 
9.2.3 
ICD PROGRAMMING 
 
 
The following programmed detection and therapy parameters should be used to optimize 
therapy delivered to the subject during the course of the study for both the Catheter Ablation 
Group (Treatment) and Control Group: 
 
ICD Programming Requirements 
Arrhythmia 
Programming Strategy 
VT Zone 
175-195 bpm 
VF Zone 
200 bpm.  ATP to 250 bpm 
Monitor Zone 
130-170 bpm 
VT Therapy 
ATP – recommended.  Programmed at 
investigators discretion 

Renal VT Version 1.3 November 2012 
 
 
17 
 
SVT 
Discriminators 
Should be ―ON‖ in VT zone.  
Programmed at investigators 
discretion. 
 
Device Specific Detection Parameters 
Arrhythmia 
Medtronic 
Boston-Scientific 
St. Jude 
Biotronik 
VF 
18/24 beats 
5s (1-25s std, but 
would be 
approx.3-10 
beats) 
18 intervals (uses 
binned counter) 
18/24 
VT 
18-20 beats 
5s 
18-20 
18-20 (must be 
VF) 
Monitor 
No effect (on 
newer devices) 
 
Monitor may 
affect detection 
 
Comments 
 
 
 
Uses the same 
criteria for 
detection and 
redetection 
 
 
 SAFETY 
        
We anticipate no significant increase in adverse events as compared to the VT ablation or 
renal angiography procedure. The local site primary investigator will oversee the safety of the 
study at his/her site.  All adverse events will be reported to the Data Coordinating Center 
(Mount Sinai School of Medicine). Adverse events will be monitored and tallied for each 50 
patients enrolled in the study (after the 20 patients enrolled during the PILOT phase), and 
presented to an independent Cardiologist (who will serve as the Data Safety Monitoring 
individual). All adverse events will be adjudicated as being either: 1) related to the renal 
denervation procedure; 2) related to the VT ablation procedure or 3) unrelated to either 
procedure. Because of the small size of this study, the DSMB will consist of one 
Cardiologist; the PI will also be present at the meetings to relate any pertinent trial 
information.  However, recommendations are solely up to the discretion of the DSMB 
 
9.3.1 Interim and Futility Analyses 
 
An interim or futility analyses will be performed after completion of the PILOT phase of this 
study: after the enrollment of 20 subjects (10 controls, 10 study group). This analysis will be 
presented to the DSMB, who has the authority to terminate the study prematurely if an 
increase in adverse events is encountered. If the DSMB determines the trial should be 
stopped early either because of efficacy or safety concerns, or otherwise modified, the DSMB 
will prepare formal written recommendations to the PI to consider final action. Moreover, any 
pressing safety concerns that the DSMB identifies will be verbally communicated to the PI as 
soon as possible, prior to written documentation. The trial will be terminated early if severe 
procedure-related adverse events occur in more than 15% of patients in the treatment arm. 
 
9.3.2 Clinical Events Committee 
 
A separate Clinical Events Committee (CEC) composed of 2 independent 
electrophysiologists will adjudicate all ICD events in this study. 
 
 

Renal VT Version 1.3 November 2012 
 
 
18 
 
 RISKS 
VT ablation will occur according to standard procedure, and therefore the risk includes that of a 
standard VT ablation. These risks include:  
Common:   
            
 
Discomfort at the site of vascular access 
 
Groin hematoma 
 
 
 Uncommon: 
 
 
Bleeding 
 
Vascular injury 
 
Thromboembolism, including renal infarction and peripheral atheroembolism. This risk is 
minimized considerably by the short duration of the procedure, as well as the use of a 
saline-irrigated ablation catheter. 
 
Risks associated with sedatives/anesthesia. 
 
Injury to adjacent structures (phrenic nerve, cardiac valves)  
 
Vascular complications (including pseudoaneurysm, AV fistula requiring surgical 
intervention) 
 
Radiation burns 
 
Pneumonia and/or sepsis 
 
Death  
 
Discomfort in the throat region  
 
Cardiac Perforation requiring drainage or surgery 
 
Injury to adjacent structures (phrenic nerve, esophagus, lung, cardiac valves)  
 
Congestive heart failure  
 
Myocardial infarction 
 
Radiation burns 
 
The potential additional risks of the RSDN procedure are anticipated to be uncommon but may include: 
 
Renal artery dissection 
 
Renal artery stenosis or occlusion  
 
Renal dysfunction potentially needing hemodialysis  
 
Thromboembolism, including renal infarction and peripheral atheroembolism. This risk is 
minimized considerably by the short duration of the procedure, as well as the use of a 
saline-irrigated ablation catheter. 
 
10.0 STUDY MANAGEMENT 
 
10.1 Study Data Collection and Processing 
The Case Report Form (CRF) is an integral part of the study and subsequent reports.  The 
CRF must be used to capture all study data recorded in the patient’s medical record.  The 
CRF must be kept current to reflect patient status during the course of the study.  Patients 
will be identified by a 5 digit number and their initials.  The investigator must keep a 
separate log of patient names and medical record numbers (or other personal identifiers) 
for their own reference. All study-related documents (CRFs, source medical records, 
regulatory binder must be kept in a secure, locked environment with access limited to 
study personnel only. 

Renal VT Version 1.3 November 2012 
 
 
19 
 
The PI is responsible for ensuring the following at his/her site: 1) adherence to the 
protocol; 2) verifying adherence to local regulations on the conduct of clinical research; 
and 3) ensuring completeness, accuracy, and consistency of the data entered in the CRF. 
Final CRFs in human readable format must be reviewed and verified for accuracy by the 
study site Principal Investigator and signed-off.  A copy of the final CRF will remain at 
the investigator’s site at the completion of the study. 
 
The CRF numbering convention is as follows: 
 
_01_-_2_ _3__4_ A -B -A 
_01_: Site # must be 2 digits (use leading zero) --- (sites 01-10) 
 
_2_ _3__4_: patient screening/enrollment # (001 – 500)—must be 3 digits 
 
A-B-A: Patient initials (if no middle initial, use dash)  
Total 5 digits and initials for enrolled patients. 
 
10.2 
Confidentiality 
Patient information will be kept confidential and managed according to the 1996 HIPAA 
guidelines. All patient information will be de-identified and stored in a secure, locked 
environment. Each patient will be given a unique subject number and will be identified 
by this number and their initials. All data used in the analysis and reporting of this 
evaluation will be without identifiable reference to the patient. Data relating to the study 
might be made available to third parties (for example in case of an audit performed by 
regulatory authorities) provided the data are treated confidential and that the patient’s 
privacy is protected.   
 
10.3 
Deviations from Protocol 
 
The investigator will not deviate from the protocol except in medical emergencies or in 
unforeseen, isolated instances where minor changes are made that will not increase the 
patient’s risk or affect the validity of the trial.  In medical emergencies, prior approval for 
protocol deviations will not be required, but the IRB/EC must be notified within five days 
of the incident. 
 
10.4 Withdrawal of Subjects 
 
A subject may withdraw from the study at any time should they choose to do so.  
Additionally, subjects may be withdrawn by the investigator if deemed appropriate due to 
safety or compliance issues. 
 
10.5 Economic Impact on Subjects 
 
The catheter-based renal sympathetic denervation procedure is part of a research study 
and is investigational. The cost of the renal sympathetic denervation procedure and 
follow-up will be the responsibility of the subject or the subject’s insurance carrier.  No 
payment will be made to the subject for taking part in this study. 
 
11.0 ETHICAL AND REGULATORY CONSIDERATIONS 
 

Renal VT Version 1.3 November 2012 
 
 
20 
 
11.1 Risk to subjects: Although it is unlikely, it is possible there may be loss of 
confidentially.  This is a typical risk of any research study.  Stenosis, dissection, and 
groin complications are possible clinical risks however they are not anticipated risks in 
this trial. 
 
11.2 Potential Benefits to Subjects: After undergoing RSDN, patients may experience 
less episodes of VT requiring ATP or shocks a result of the expected reduction in whole 
body norepinephrine spillover and sympathetic nerve activity. 
 
 
11.3 Role of the Coordinating Center 
 
As principal investigator and study sponsor of this clinical study, Vivek Y. Reddy, MD 
assumes the overall responsibility for the conduct of the study, including assurance that 
the study meets national and institutional guidelines for study conduct.  In this study, 
Vivek Y. Reddy, MD will have certain direct responsibilities and will delegate other 
responsibilities to his staff at the Coordinating Center, the Mount Sinai Hospital. 
Together, the coordinating center will: 1) ensure adherence to the national and 
institutional regulations; 2) develop and distribute protocols and case report forms; 3) 
coordinate data organization; 4) perform statistical analyses. 
 
11.4 Maintaining Records (21 CFR 812. 140 (B)) 
 
The Coordinating center will maintain copies of correspondence, data, shipment of 
devices, adverse device effects and other records related to the clinical trial.   
 
11.5 Site Record Retention Policy 
 
All clinical sites will maintain study records for two years after research termination. 
 
11.6 Institutional Review Board (IRB) / Ethics Committee (EC) Information 
 
This protocol and the informed consent must be reviewed and approved by the 
appropriate IRB/EC where the trial is to be conducted before enrollment of patients.  
Changes to the protocol that may increase the risk or present new risks to the patient, or 
may adversely affect the validity of the trial, must be approved in writing by the IRB/EC 
before the change is made. 
 
The study site Principal Investigator(s) is responsible for submitting and obtaining initial 
and continuing review (at intervals not greater than once a year) of the trial by their 
IRB/EC. 
 
 
12.0  
DATA HANDLING 
 
Information about patients will be kept confidential and managed according to the requirements 
of the United States of American Health Insurance Portability and Accountability Act of 1996 
(HIPAA). Those regulations require a signed patient authorization informing the patient of the 
following:  
 
1. What protected health information (PHI) will be collected from patients. 

Renal VT Version 1.3 November 2012 
 
 
21 
 
2. Who will have access to that information and why.  
3. Who will use or disclose that information.  
4. The rights of a research patient to revoke their authorization for use of their PHI.  
 
In the event that a patient revokes authorization to collect or use PHI, the investigator, by 
regulation, retains the ability to use all information collected prior to the revocation of patient 
authorization. For patients that have revoked authorization to collect or use PHI, attempts should 
be made to obtain permission to collect at least vital status (i.e. that the patient is alive) at the end 
of their scheduled registry period. 
 
 
In order to ensure patient confidentiality, all case report forms and patient information (CT / MRI, 
if reviewed), fluoroscopic and endoscopic images, ECGs) will be de-identified and replaced with 
a unique patient identifier.  Information will be stored in the office of the local study coordinator, 
which will be kept in a secure location. The research study coordinators, principal investigator 
and co-investigators will be the only people with access to this data. All data will be stored 
without any patient information apart from the unique three digit patient identifier.  There will be 
a code sheet that will link the de-identified data back to the subjects. This will be encrypted and 
password-protected. One copy will be stored in the primary investigator’s computer, and another 
in the research coordinator’s computer.  
 

Renal VT Version 1.3 November 2012 
 
 
22 
 
References: 
 
1. 
Zipes DP, Wellens HJ. Sudden cardiac death. Circulation 1998;98:2334-51. 
2. 
Straus SM, Bleumink GS, Dieleman JP, van der Lei J, Stricker BH, Sturkenboom MC. 
The incidence of sudden cardiac death in the general population. Journal of clinical 
epidemiology 2004;57:98-102. 
3. 
Kong MH, Fonarow GC, Peterson ED, et al. Systematic review of the incidence of 
sudden cardiac death in the United States. Journal of the American College of Cardiology 
2011;57:794-801. 
4. 
Epstein AE, DiMarco JP, Ellenbogen KA, et al. ACC/AHA/HRS 2008 Guidelines for 
Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of 
Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee 
to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac 
Pacemakers and Antiarrhythmia Devices) developed in collaboration with the American 
Association for Thoracic Surgery and Society of Thoracic Surgeons. Journal of the American 
College of Cardiology 2008;51:e1-62. 
5. 
Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-
defibrillator for congestive heart failure. The New England journal of medicine 2005;352:225-
37. 
6. 
Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in 
patients with myocardial infarction and reduced ejection fraction. The New England journal of 
medicine 2002;346:877-83. 
7. 
von Kanel R, Baumert J, Kolb C, Cho EY, Ladwig KH. Chronic posttraumatic stress and 
its predictors in patients living with an implantable cardioverter defibrillator. Journal of affective 
disorders 2011;131:344-52. 
8. 
Connolly SJ, Dorian P, Roberts RS, et al. Comparison of beta-blockers, amiodarone plus 
beta-blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: 
the OPTIC Study: a randomized trial. JAMA : the journal of the American Medical Association 
2006;295:165-71. 
9. 
Aliot EM, Stevenson WG, Almendral-Garrote JM, et al. EHRA/HRS Expert Consensus 
on Catheter Ablation of Ventricular Arrhythmias: developed in a partnership with the European 
Heart Rhythm Association (EHRA), a Registered Branch of the European Society of Cardiology 
(ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of 
Cardiology (ACC) and the American Heart Association (AHA). Heart rhythm : the official 
journal of the Heart Rhythm Society 2009;6:886-933. 
10. 
Reddy VY, Reynolds MR, Neuzil P, et al. Prophylactic catheter ablation for the 
prevention of defibrillator therapy. The New England journal of medicine 2007;357:2657-65. 
11. 
Krum H, Schlaich M, Whitbourn R, et al. Catheter-based renal sympathetic denervation 
for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet 
2009;373:1275-81. 
12. 
Schlaich MP, Sobotka PA, Krum H, Lambert E, Esler MD. Renal sympathetic-nerve 
ablation for uncontrolled hypertension. The New England journal of medicine 2009;361:932-4. 
13. 
Lown B, Verrier RL. Neural activity and ventricular fibrillation. The New England 
journal of medicine 1976;294:1165-70. 

Renal VT Version 1.3 November 2012 
 
 
23 
 
14. 
Han P, Cai W, Wang Y, et al. Catecholaminergic-induced arrhythmias in failing 
cardiomyocytes associated with human HRCS96A variant overexpression. American journal of 
physiology Heart and circulatory physiology 2011;301:H1588-95. 
15. 
van der Werf C, Zwinderman AH, Wilde AA. Therapeutic approach for patients with 
catecholaminergic polymorphic ventricular tachycardia: state of the art and future developments. 
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working 
groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European 
Society of Cardiology 2011. 
16. 
Watanabe H, Knollmann BC. Mechanism underlying catecholaminergic polymorphic 
ventricular tachycardia and approaches to therapy. Journal of electrocardiology 2011;44:650-5. 
17. 
Smithwick RH, Thompson JE. Splanchnicectomy for essential hypertension; results in 
1,266 cases. Journal of the American Medical Association 1953;152:1501-4. 
18. 
Schlaich MP, Lambert E, Kaye DM, et al. Sympathetic augmentation in hypertension: 
role of nerve firing, norepinephrine reuptake, and Angiotensin neuromodulation. Hypertension 
2004;43:169-75. 
19. 
Kenchaiah S, Pfeffer MA. Cardiac remodeling in systemic hypertension. The Medical 
clinics of North America 2004;88:115-30. 
20. 
Ukena C, Bauer A, Mahfoud F, et al. Renal sympathetic denervation for treatment of 
electrical storm: first-in-man experience. Clinical research in cardiology : official journal of the 
German Cardiac Society 2011.