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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Heart Failure; Cardio-Renal Syndrome
• Intervention / Treatment: Procedure: Renal arteriography followed by renal denervation; Procedure: Sham Renal arteriography

• Study Type: Interventional
• Enrollment (Anticipated): 144
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Felix Mahfoud, MD; Phone Number: +49-6841-16-15911; Email: Felix.Mahfoud@uks.eu

Study Locations

• Germany
  • Saarland
    • Homburg/Saar, Saarland, Germany, 66421
      • Recruiting
      • Saarland University Medical Center, Department for Internal Medicine III
      • Contact: Felix Mahfoud, MD; Phone Number: +49-6841-16-15911; Email: Felix.Mahfoud@uks.eu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Universität des Saarlandes
• Collaborators: Interdisciplinary Center Clinical Trials (IZKS), University Medical Center Mainz
• Investigators: Principal Investigator: Felix Mahfoud, MD, Saarland University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2022
• Primary Completion (Anticipated): May 1, 2025
• Study Completion (Anticipated): May 1, 2026

Study Registration Dates

• First Submitted: June 24, 2021
• First Submitted That Met QC Criteria: June 30, 2021
• First Posted (Actual): July 1, 2021

Study Record Updates

• Last Update Posted (Actual): November 4, 2022
• Last Update Submitted That Met QC Criteria: November 3, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Renal Insufficiency; Heart Failure; Cardio-Renal Syndrome
• Other Study ID Numbers: RE-ADAPT-HF (2021)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No