Renal Denervation in Patients With Chronic Heart Failure

NCT ID: NCT02085668

Last Updated: 2023-05-26

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2019-05-31

Brief Summary

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

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.

Conditions

Chronic Heart Failure; Cardio-Renal Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Group

Renal denervation and maintenance of heart failure medications

Group Type: EXPERIMENTAL

Renal denervation (Symplicity™)

Intervention Type: DEVICE

Delivery of radiofrequency through the wall of the renal artery to disrupt the surrounding renal nerves under angiography control

Control Group

Maintenance of heart failure medications with option for cross-over renal denervation treatment after 6-months

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Renal denervation (Symplicity™)

Delivery of radiofrequency through the wall of the renal artery to disrupt the surrounding renal nerves under angiography control

Intervention Type: DEVICE

Other Intervention Names

Renal denervation with Symplicity™ Renal Denervation System

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Saarland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Böhm, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Saarland

Locations

Paracelsus Medical University

Salzburg, , Austria

University Heart Center Freiburg Bad Krozingen

Bad Krozingen, , Germany

German Heart Institute Berlin

Berlin, , Germany

University Hospital Bonn

Bonn, , Germany

University Hospital Gießen Marburg

Giessen, , Germany

University Hospital Heidelberg

Heidelberg, , Germany

University Hospital Saarland

Homburg/Saar, , Germany

University of Leipzig, Heart Center

Leipzig, , Germany

University Hospital Tübingen

Tübingen, , Germany

Sahlgrenska University Hospital

Gothenburg, , Sweden

University Hospital Zurich

Zurich, , Switzerland

Countries

Austria; Germany; Sweden; Switzerland

Other Identifiers

CIV-13-10-011660

Identifier Type: OTHER

Identifier Source: secondary_id

RE-ADAPT-HF

Identifier Type: -

Identifier Source: org_study_id