Renal Denervation in Patients With Chronic Heart Failure

A Prospective, Multicenter, Randomized, Open-label, Feasibility, Safety and Efficacy Study of Renal Denervation in Patients With Chronic Heart Failure (CHF)

The purpose of the trial is to investigate the safety and effectiveness of renal denervation for the treatment of chronic heart failure (CHF).

Study Overview

• Status: Withdrawn
• Conditions: Chronic Heart Failure; Cardio-Renal Syndrome
• Intervention / Treatment: Device: Renal denervation (Symplicity™)

Detailed Description

Heart failure is a major public health problem. It is associated with high mortality, frequent hospitalization and represents a large cost to the health care system. Therapies to ameliorate the high mortality and morbidity of heart failure have focused on abrogation of activated neurohormonal systems associated with this condition. These systems include the renin-angiotensin-aldosterone system and the sympathetic nervous system.

Strategies to ameliorate sympathetic activation have primarily focused on blockade of the beta-adrenoceptors that mediate the adverse effects of activation of this system upon the myocardium. This has been a highly successful strategy with beta-blockers resulting in an approximately 35% reduction in mortality as well as improvements in hospitalization and quality of life and attenuation of disease progression.

However, less than full blockade of the effects of the sympathetic nervous system is achieved with the use of conventional doses of beta-blockers. Moreover, a not insignificant fraction of patients are unable to tolerate beta-blockers or are not able to have them up-titrated to target effective doses, in large part because of the systemic nature of these agents, whereas renal denervation allows the selective removal of the kidney's contribution to central sympathetic drive without blunting other compensatory mechanisms.

The renin-angiotensin-aldosterone axis has also been found to be a key system involved in heart failure disease progression and it too 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.

Cardiorenal syndrome is a major comorbid condition of patients with advanced chronic heart failure. In the setting of renal hypoperfusion and/or activation of neurohormonal and cytokine systems there is a reduction in glomerulofiltration. Renal function has been found to be a major determine of prognosis in these patients. Strategies to ameliorate cardiorenal syndrome are being actively pursued. There is considerable a priori evidence to suggest that the sympathetic nervous system, in particular renal sympathetic, is a key factor to the progression of cardiorenal syndrome and impaired tubulo-glomerular feedback. In particular renal sympathetics reduce renal perfusion through vascular alpha adrenergic receptor stimulation as well as, indirectly, through stimulation of local release of adenosine causing afferent glomerular arteriole constriction. We hypothesize that by disrupting renal sympathetic afferent and efferent activity these salutary adenosine inhibitory mediated effects will be demonstrated using the renal denervation approach.

A number of studies with hypertension patients indicate that the Symplicity Catheter System can safely denervate the kidney without significant periprocedural complications.

In a small first-in man pilot study, involving seven normotensive patients with chronic heart failure, six months after renal denervation their 6-min walk distance improved significantly and the patients' self-assessment of well-being also improved. No procedural or post procedural complications following renal denervation in patients in 6 months of intensive follow-up were found.

The investigators believe that therapeutic renal denervation using the Symplicity Catheter is a promising therapy for patients with elevated sympathetic activity, as in CHF.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Felix Mahfoud, MD; Phone Number: +49 6841 16 21346; Email: felix.mahfoud@uks.eu
• Study Contact Backup: Name: Christian D Ukena, MD; Phone Number: +49 6841 16 21346; Email: christian.ukena@uks.eu

Study Locations

• Austria
  • Salzburg, Austria, 5020
    • Paracelsus Medical University
    • Principal Investigator: Uta C Hoppe, MD
    • Sub-Investigator: Mathias Brandt, MD
• Germany
  • Bad Krozingen, Germany, 79189
    • University Heart Center Freiburg Bad Krozingen
    • Sub-Investigator: Ulrich Beschorner, MD
  • Berlin, Germany, 13353
    • German Heart Institute Berlin
    • Principal Investigator: Eckart Fleck, MD
    • Sub-Investigator: Sebastian Kelle, MD
  • Bonn, Germany, 53127
    • University Hospital Bonn
    • Sub-Investigator: Katja Twelker, MD
  • Gießen, Germany, 35392
    • University Hospital Gießen Marburg
    • Sub-Investigator: Oliver Dörr, MD
  • Heidelberg, Germany, 69120
    • University Hospital Heidelberg
    • Principal Investigator: Erwin Blessing, MD
    • Sub-Investigator: Oliver Müller, MD
  • Homburg/Saar, Germany, 66421
    • University hospital Saarland
    • Sub-Investigator: Felix Mahfoud, MD
  • Leipzig, Germany, 04289
    • University of Leipzig, Heart Center
    • Sub-Investigator: Ulrike Müller, MD
  • Tübingen, Germany, 72076
    • University Hospital Tübingen
    • Sub-Investigator: Tobias Geisler, MD
• Sweden
  • Gothenburg, Sweden, 41345
    • Sahlgrenska University Hospital
    • Principal Investigator: Bert Andersson, MD
    • Principal Investigator: Bengt Rundqvist, MD
• Switzerland
  • Zürich, Switzerland, 8091
    • University Hospital Zurich
    • Principal Investigator: Thomas Lüscher, MD
    • Sub-Investigator: Isabella Sudano, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• New York Heart Association Class II-III symptoms of chronic heart failure
• Systolic left ventricular dysfunction as assessed by echocardiogram with left ventricular ejection fraction in a range of 10%- 40%.
• GFR >30 mL/min/1.73m2
• Brain natriuretic Peptide (BNP) >100 pg/ml or N terminal (NT)-Pro-BNP >400 pg/ml.
• Optimal medical therapy according to current guidelines for CHF management. Treatment for HF must be stable (including drug and dose) for at least 4 weeks prior to procedure, with the exception of diuretics, where stability is required for at least 2 weeks.
• others

Exclusion Criteria:

• Renal arterial anatomy that is ineligible for treatment
• CHF caused by pericarditis or by acute myocarditis or by endocrine diseases.
• Myocardial infarction, unstable angina pectoris, or a cerebrovascular accident within three 12 weeks of the screening visit.
• Office systolic BP at screening less than 90 mmHg
• Primary pulmonary hypertension.
• Clinically significant cardiac structural valvular disease, unless corrected by a properly functional prosthetic valve
• Major surgery, including bariatric surgery, in the previous 12 weeks before baseline.
• Contrast media administration in the previous 30 days before baseline.
• Known hypersensitivity to material of the Symplicity Catheter.
• Inpatient hospitalization for decompensated HF in the previous 60 days before baseline.
• others

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group; Renal denervation and maintenance of heart failure medications	Device: Renal denervation (Symplicity™); Delivery of radiofrequency through the wall of the renal artery to disrupt the surrounding renal nerves under angiography control; Other Names: Renal denervation with Symplicity™ Renal Denervation System
No Intervention: Control Group; Maintenance of heart failure medications with option for cross-over renal denervation treatment after 6-months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of renal denervation with the Symplicity Catheter System with special consideration of clinically significant periprocedural adverse events in CHF patients	Number of complications associated with the delivery and/or use of the Symplicity Catheter (e.g., vascular injury and bleeding complications, access site hematoma, etc.). Vital signs, blood and urine measurements taken before, during and after the denervation procedure	Baseline visit for treatment group, month 6 visit for control group

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physiologic response to renal denervation: ventricular function	Measured by echocardiography at 6 months	From denervation prodecure to 6 months after renal denervation procedure
Physiologic Response to renal denervation: renal function	Calculated by glomerular filtration rate (GFR) at 6 months	From denervation prodecure to 6 months after renal denervation procedure
Physiologic Response to renal denervation: symptomatology/Quality of Life	Measured by EuroQol - 5 dimensions (EQ-5D) and by Kansas City Cardiomyopathy questionnaires at 6 months after renal denervation	From denervation prodecure to 6 months after renal denervation procedure
Physiologic Response to renal denervation: additional parameters	Composite measure	From denervation prodecure to 6 months after renal denervation procedure

Collaborators and Investigators

• Sponsor: University Hospital, Saarland
• Investigators: Principal Investigator: Michael Böhm, MD, University Hospital, Saarland

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Estimated): December 1, 2015
• Study Completion (Estimated): May 1, 2019

Study Registration Dates

• First Submitted: March 10, 2014
• First Submitted That Met QC Criteria: March 12, 2014
• First Posted (Estimated): March 13, 2014

Study Record Updates

• Last Update Posted (Actual): May 26, 2023
• Last Update Submitted That Met QC Criteria: May 24, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Chronic Heart Failure; Renal Denervation; Sympathetic activation; Cardio-Renal Syndrome; Symplicity
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Heart Failure; Cardio-Renal Syndrome
• Other Study ID Numbers: RE-ADAPT-HF; CIV-13-10-011660 (Other Identifier: EUDAMED Number European Databank on Medical Devices)