A Prospective, Multicenter, Randomized, Blinded, Sham-controlled, Feasibility Study of Renal Denervation in Patients With Chronic Heart Failure

Study Overview
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Brief Summary
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The renin-angiotensin-aldosterone axis has been found to be a key system involved in heart failure disease progression and it may be inhibited by renal sympathetic denervation. Therefore, a clear need exists for further strategies to beneficially manipulate the sympathetic activation that is characteristic of the heart failure disease process. The combined experience in the pilot studies and the EU randomized, controlled study indicates that the Paradise Catheter System can safely denervate renal sympathetic nerves of the kidney without significant periprocedural complications. Preliminary results of a pilot study of catheter-based renal denervation in a small number of CHF patients did not show evidence of safety issues but suggest improvements in CHF symptoms. This trial will explore the safety and feasibility of renal denervation in a significantly higher number of patients with chronic heart failure. Both inter-individual and intra-individual controls will be used in order to obtain sufficient data and to in order to enable both treatment and control group to receive renal denervation. Additionally, this feasibility trial to describe the safety and feasibility of renal denervation in patients with elevated sympathetic activity as in patients with chronic heart failure, will further the understanding of the role of renal nerves in the control of chronic heart failure and the pathogenesis of both ventricular remodeling and cardio-renal syndrome.

Official Title
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A Prospective, Multicenter, Randomized, Blinded, Sham-controlled, Feasibility Study of Renal Denervation in Patients With Chronic Heart Failure

Conditions
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Chronic Heart Failure, Cardio-Renal Syndrome

Intervention / Treatment
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* Procedure: Renal arteriography followed by renal denervation
* Procedure: Sham Renal arteriography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with CHF diagnosed for at least 3 months prior to consent 6-min walk distance ≤350 m NYHA Class II-III symptoms of CHF Systolic left ventricular dysfunction as assessed by echocardiogram with left ventricular ejection fraction <45% eGFR calculated (CKD-EPI) >30 ml/min/1.73 m2 NT-pro-BNP >450 pg/ml, >900 pg/ml for patients with atrial fibrillation Optimal medical drug therapy according to current guidelines for CHF management. This medication may include loop diuretics, ACEi/ARBs, ARNI, SGLT-2 inhibitors, aldosterone antagonists, and beta-blockers, unless intolerance to any of the above is documented. Treatment for HF must be stable (including drug and dose) for 4 weeks prior to randomization, except diuretics (2 weeks stable) Appropriate use of medical devices such as an implantable cardioverter defibrillator (ICD) or a cardiac resynchronization therapy (CRT) consistent with prevailing local or international guidelines, and if a device is required, it must have been implanted for at least 3 months prior to consent for CRT and 1 month prior to consent for ICD Age ≥18 years and ≤80 years Exclusion Criteria: Renal arterial anatomy that is ineligible for treatment Myocardial infarction, unstable angina pectoris, or a cerebrovascular accident within 12 weeks prior to consent Office systolic BP at screening <90 mmHg Clinically significant cardiac structural valvular disease, unless corrected by a properly functional prosthetic valve Hypertrophic obstructive cardiomyopathy Major surgery in the previous 12 weeks prior to consent Hospitalization for decompensated CHF in the <30 days prior to consent Parenteral therapy for the treatment of CHF Respiratory support (excluding sleep apnea therapy) Left ventricular assist or planned heart transplantation Patient is pregnant, nursing, or planning to be pregnant Ineligibility to consent Primary pulmonary hypertension (systolic PAP >70 mmHg) BMI ≥40 kg/m² Any condition that would contraindicate the assessment of 6-min walk distance. Patient has type I diabetes mellitus

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Crossover Assignment
Interventional Model Description: Prospective, randomized, double-blind, sham-controlled, multicenter, feasibility study. Patients will be screened for meeting eligibility and centrally randomized to receive either renal denervation or sham procedure. Best medical therapy will be provided to all patients. Optional cross-over after 12 months for sham-group patients. Thus, there is an intra-individual control in patients of the control group and all of the randomized patients are entitled to receive study treatment.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>Renal denervation and maintenance of heart failure medications | Procedure: Renal arteriography followed by renal denervation<br>* Renal arteriography followed by renal denervation<br>|
| Sham Comparator: Control Group<br>Sham intervention, maintenance of heart failure medications with option for cross-over renal denervation treatment after 12 months | Procedure: Sham Renal arteriography<br>* Renal arteriography only<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 Minute Walk Test | Change in 6-min walk distance | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NT-proBNP | Change in plasma NT-proBNP values | 6 months | 
| KCCQ | Change in Overall Summary Score measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) | 6 months | 
| EQ-5D | Change in Chronic Heart Failure Questionnaire Self-Administered Standardized format (CHQ-SAS) dyspnea score | 6 months | 
| eGFR | chronic eGFR slope defined as eCRF | 6 months |