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

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

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.

Study Overview

• Status: Terminated
• Conditions: Arrhythmias, Cardiac
• Intervention / Treatment: Procedure: RNS and RDN

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Overijssel
    • Zwolle, Overijssel, Netherlands, 8025AB
      • A. Elvan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: CPVT; catecholaminergic polymorphic ventricular tachycardia (CPVT) patients	Procedure: RNS and RDN; The patients will undergo electrical renal nerve stimulation and subsequently renal nerve denervation
Other: long QT syndrome; long QT syndrome patients	Procedure: RNS and RDN; The patients will undergo electrical renal nerve stimulation and subsequently renal nerve denervation
Other: ARVC; arrhythmogenic right ventricular cardiomyopathy (ARVC) patients	Procedure: RNS and RDN; The patients will undergo electrical renal nerve stimulation and subsequently renal nerve denervation
Other: HCM; hypertrophic cardiomyopathy (HCM) patients	Procedure: RNS and RDN; The patients will undergo electrical renal nerve stimulation and subsequently renal nerve denervation
Other: DCM; dilated non-ischemic cardiomyopathy (DCM) patients	Procedure: RNS and RDN; The patients will undergo electrical renal nerve stimulation and subsequently renal nerve denervation
Other: ICM; ischemic cardiomyopathy (ICM) patients	Procedure: RNS and RDN; The patients will undergo electrical renal nerve stimulation and subsequently renal nerve denervation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Induction of ventricular arrhythmias (e.g. ventricular tachycardia and ventricular fibrillation)	Induction of ventricular arrhythmias in response to RNS prior to RDN and absence of RNS induced ventricular arrhythmias after RDN	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.
Development of ventricular arrhythmia	Development of ventricular arrhythmia during exercise stress testing performed 6 months after procedure/intervention	6 months after procedure/intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first detection of ventricular arrhythmia or appropriate ICD therapy	Time to first detection of ventricular arrhythmia or appropriate ICD therapy with the monitoring period starting immediately after the intervention.	procedure/intervention-12 month follow up
Changes in ventricular refractoriness (frequency)	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.	procedure/intervention
Changes in ventricular refractoriness (duration)	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.	procedure/intervention
Number of ventricular arrhythmias	Inducibility (number) of ventricular arrhythmias to programmed electrical stimulation in the setting of routine electrophysiological study before and after RDN.	procedure/intervention
Ventricular arrhythmia burden	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.	procedure/intervention- 6,12 months follow up
Blood pressure	Blood pressure at 6 and 12 months after the intervention	6-12 months follow up
Number of (Supra-)Ventricular arrhythmias induced by exercise testing	Number of (Supra-)Ventricular arrhythmias induced by exercise testing	baseline- 6 months follow up
(Supra-)Ventricular arrhythmias response changes (frequency) induced by exercise testing	(Supra-)Ventricular arrhythmias response changes (frequency, beats/min) induced by exercise testing	baseline- 6 months follow up
(Supra-)Ventricular arrhythmias response changes (duration) induced by exercise testing	(Supra-)Ventricular arrhythmias response changes (duration, sec) induced by exercise testing	baseline- 6 months follow up
Changes in heart rate variability	Changes in heart rate variability measures tested by Holter monitoring compared to measurement before the intervention	baseline- 3, 6 and 12 month follow up
Changes in prevalence of events	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.	12 month before procedure/intervention-12 month follow up
Change in blood pressure	Change in blood pressure compared to measurement before the intervention	baseline- 6, 12 month follow up
Heart rate response changes induced by exercise testing	Heart rate response changes induced by exercise testing	baseline- 6 months follow up
Blood pressure response changes induced by exercise testing	Blood pressure response changes induced by exercise testing	baseline-6 months follow up

Collaborators and Investigators

• Sponsor: Diagram B.V.
• Investigators: Principal Investigator: Arif Elvan, MD, PhD, Isala, department of Cardiology

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2015
• Primary Completion (Actual): May 4, 2020
• Study Completion (Actual): May 4, 2020

Study Registration Dates

• First Submitted: June 10, 2016
• First Submitted That Met QC Criteria: August 1, 2016
• First Posted (Estimate): August 4, 2016

Study Record Updates

• Last Update Posted (Actual): May 6, 2020
• Last Update Submitted That Met QC Criteria: May 4, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Denervation; Renal Artery
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac
• Other Study ID Numbers: 9218

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No