Renal Nerve Stimulation and Renal Denervation in Patients With Sympathetic Ventricular Arrhythmias (Redress VT)

• ClinicalTrials.gov Identifier: NCT02856373
• Recruitment Status: Terminated
• First Posted: August 4, 2016
• Last Update Posted: May 6, 2020
• Sponsor: Diagram B.V.
• Information provided by (Responsible Party): Diagram B.V.

Tracking Information

• First Submitted Date: June 10, 2016
• First Posted Date: August 4, 2016
• Last Update Posted Date: May 6, 2020
• Actual Study Start Date: March 3, 2015
• Actual Primary Completion Date: May 4, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 1, 2016)

• Induction of ventricular arrhythmias (e.g. ventricular tachycardia and ventricular fibrillation) [ Time Frame: A few minutes before RDN RNS will be performed. Time frame before RDN: 0-10 min. after RNS and before RDN. Time frame after RDN: 0-10 min. ]
  Induction of ventricular arrhythmias in response to RNS prior to RDN and absence of RNS induced ventricular arrhythmias after RDN
• Development of ventricular arrhythmia [ Time Frame: 6 months after procedure/intervention ]
  Development of ventricular arrhythmia during exercise stress testing performed 6 months after procedure/intervention

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 1, 2016)

• Time to first detection of ventricular arrhythmia or appropriate ICD therapy [ Time Frame: procedure/intervention-12 month follow up ]
  Time to first detection of ventricular arrhythmia or appropriate ICD therapy with the monitoring period starting immediately after the intervention.
• Changes in ventricular refractoriness (frequency) [ Time Frame: procedure/intervention ]
  Changes in ventricular refractoriness (frequency, beats/min) to programmed electrical stimulation in the setting of routine electrophysiological study before and directly (0-10 min) after RDN.
• Changes in ventricular refractoriness (duration) [ Time Frame: procedure/intervention ]
  Changes in ventricular refractoriness (duration, sec) to programmed electrical stimulation in the setting of routine electrophysiological study before and directly (0-10 min) after RDN.
• Number of ventricular arrhythmias [ Time Frame: procedure/intervention ]
  Inducibility (number) of ventricular arrhythmias to programmed electrical stimulation in the setting of routine electrophysiological study before and after RDN.
• Ventricular arrhythmia burden [ Time Frame: procedure/intervention- 6,12 months follow up ]
  Ventricular arrhythmia burden after 6 and 12 months of follow-up in patients with ICD or continuous rhythm monitoring with a loop recorder. The monitoring period starts immediately after the intervention.
• Blood pressure [ Time Frame: 6-12 months follow up ]
  Blood pressure at 6 and 12 months after the intervention
• Number of (Supra-)Ventricular arrhythmias induced by exercise testing [ Time Frame: baseline- 6 months follow up ]
  Number of (Supra-)Ventricular arrhythmias induced by exercise testing
• (Supra-)Ventricular arrhythmias response changes (frequency) induced by exercise testing [ Time Frame: baseline- 6 months follow up ]
  (Supra-)Ventricular arrhythmias response changes (frequency, beats/min) induced by exercise testing
• (Supra-)Ventricular arrhythmias response changes (duration) induced by exercise testing [ Time Frame: baseline- 6 months follow up ]
  (Supra-)Ventricular arrhythmias response changes (duration, sec) induced by exercise testing
• Changes in heart rate variability [ Time Frame: baseline- 3, 6 and 12 month follow up ]
  Changes in heart rate variability measures tested by Holter monitoring compared to measurement before the intervention
• Changes in prevalence of events [ Time Frame: 12 month before procedure/intervention-12 month follow up ]
  Changes in prevalence of events (hospital admission for VT or appropriate ICDshock) in the period of one year after intervention compared to a one year period before intervention.
• Change in blood pressure [ Time Frame: baseline- 6, 12 month follow up ]
  Change in blood pressure compared to measurement before the intervention
• Heart rate response changes induced by exercise testing [ Time Frame: baseline- 6 months follow up ]
  Heart rate response changes induced by exercise testing
• Blood pressure response changes induced by exercise testing [ Time Frame: baseline-6 months follow up ]
  Blood pressure response changes induced by exercise testing

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Renal Nerve Stimulation and Renal Denervation in Patients With Sympathetic Ventricular Arrhythmias
• Official Title: Renal Nerve Stimulation and Renal Denervation in Patients With Sympathetic Ventricular Arrhythmias: an Investigator Initiated Trial

Brief Summary

Rationale:

Sympathetic activity plays an important role in the pathogenesis of ventricular tachyarrhythmia. Previous studies have shown evidence of significant heritable influences on individual responses to adrenergic stimulation. Catheter-based renal sympathetic denervation (RDN) is a novel treatment option for patients with resistant hypertension, proved to reduce local and whole-body sympathetic activity. The investigators hypothesize that percutaneous transluminal electrical stimulation of the sympathetic nerve bundles in the renal arteries will cause ventricular arrhythmias and renal denervation will suppress these arrhythmias in patients with sympathetic ventricular arrhythmias.

Objective:

This study will investigate the effects of renal nerve stimulation before and after percutaneous transluminal RDN on cardiac excitable properties including induction of ventricular tachy-arrhythmias before and after RDN in six studies, i.e. patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome and arrhythmogenic right ventricular cardiomyopathy (ARVC), sympathetically driven ventricular arrhythmias, hypertrophic cardiomyopathy (HCM), dilated non-ischemic cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM). The aim of the six studies is to assess the anti-arrhythmic effects of RDN in patients with sympathetic ventricular tachy-arrhythmias.

Study design:

Investigator initiated, multi centre, six pretest-posttest design studies.

Study population:

Patients with recurrent sympathetically driven ventricular arrhythmia despite optimal pharmacological therapy. Patients should be diagnosed with CPVT and certain types of long QT syndrome, ARVC, HCM, DCM and ICM. Eligible patients will be in the age category of 18-85 year.

Intervention:

RDN will be performed according to routine clinical practice. Prior to the ablation procedure, catheter mapping of the renal arteries will be performed according to routine clinical practice. Clinical and biological responses to transluminal electrical renal nerve stimulation will be assessed before and after RDN.

Study endpoints:

• Main procedural study endpoint: Induction of ventricular arrhythmias in response to renal nerve stimulation prior to RDN and absence of renal nerves stimulation induced ventricular arrhythmias after RDN.
• Main clinical study endpoint: Development of ventricular arrhythmia during exercise stress testing performed 6 months after procedure.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

In several studies, it was shown that RDN was safe. The intervention resulted in significantly better control of blood pressure with less medication, and beneficial changes in heart rate variability, autonomic sympathetic balance, renal arteriolar function, and a higher success of atrial fibrillation prevention. In case reports and case series, RDN had a favourable effect in patients with sympathetic drug refractory ventricular tachy-arrhythmias.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Arrhythmias, Cardiac

Intervention

Procedure: RNS and RDN

The patients will undergo electrical renal nerve stimulation and subsequently renal nerve denervation

Study Arms

• CPVT
  catecholaminergic polymorphic ventricular tachycardia (CPVT) patients
  Intervention: Procedure: RNS and RDN
• long QT syndrome
  long QT syndrome patients
  Intervention: Procedure: RNS and RDN
• ARVC
  arrhythmogenic right ventricular cardiomyopathy (ARVC) patients
  Intervention: Procedure: RNS and RDN
• HCM
  hypertrophic cardiomyopathy (HCM) patients
  Intervention: Procedure: RNS and RDN
• DCM
  dilated non-ischemic cardiomyopathy (DCM) patients
  Intervention: Procedure: RNS and RDN
• ICM
  ischemic cardiomyopathy (ICM) patients
  Intervention: Procedure: RNS and RDN

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: May 4, 2020): 9
• Original Estimated Enrollment (submitted: August 1, 2016): 60
• Actual Study Completion Date: May 4, 2020
• Actual Primary Completion Date: May 4, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. The patient is willing and able to comply with the protocol and has provided written informed consent.
2. The patient falls within the target group as stated in 4.1.
3. Patient is an acceptable candidate for RDN treatment
4. Patient is 18-85 years of age
5. Documentation of ventricular arrhythmia (ECG, rhythm strip or ICD interrogation)

Exclusion Criteria:

1. Contraindication to anticoagulation therapy or heparin.
2. Previous selective cardiac sympathetic denervation or previous RDN procedure.
3. Acute coronary syndrome, cardiac surgery, PCI or stroke within 3 months prior to enrolment.
4. Untreated hypothyroidism or hyperthyroidism.
5. More than grade 1/3 valvular regurgitation and/or significant valve stenosis (moderate or severe).
6. Severe LV dysfunction (LVEF <20% and/or grade 3/4 diastolic dysfunction).
7. Enrolment in another investigational drug or device study.
8. Woman currently pregnant or breastfeeding or not using reliable contraceptive measures during fertile age.
9. Mental or physical inability to participate in the study.
10. Planned cardiovascular intervention.
11. Life expectancy ≤ 12 months.
12. Renal artery stenosis >50% of the arterial lumen, or renal artery lumen ≤3 mm.
13. Complex renal artery

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT02856373
• Other Study ID Numbers: 9218
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Diagram B.V.
• Study Sponsor: Diagram B.V.
• Collaborators: Not Provided

Investigators

• Principal Investigator: Arif Elvan, MD, PhD; Isala, department of Cardiology

• PRS Account: Diagram B.V.
• Verification Date: May 2020