Clinical trial NCT02085668: Renal Denervation in Patients With Chronic Heart Failure
Official title: A Prospective, Multicenter, Randomized, Open-label, Feasibility, Safety and Efficacy Study of Renal Denervation in Patients With Chronic Heart Failure (CHF)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Chronic Heart Failure
Cardio-Renal Syndrome
Keywords: Chronic Heart Failure
Cardio-Renal Syndrome
Renal Denervation
Symplicity
Sympathetic activation
Lead sponsor: Universität des Saarlandes
Sponsor class: OTHER
First posted: 2014-03-13
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Safety of renal denervation with the Symplicity Catheter System with special consideration of clinically significant periprocedural adverse events in CHF patients
timeFrame: Baseline visit for treatment group, month 6 visit for control group
Secondary outcomes:
measure: Physiologic response to renal denervation: ventricular function
timeFrame: From denervation prodecure to 6 months after renal denervation procedure
measure: Physiologic Response to renal denervation: renal function
timeFrame: From denervation prodecure to 6 months after renal denervation procedure
measure: Physiologic Response to renal denervation: symptomatology/Quality of Life
timeFrame: From denervation prodecure to 6 months after renal denervation procedure
measure: Physiologic Response to renal denervation: additional parameters
timeFrame: From denervation prodecure to 6 months after renal denervation procedure
Other outcomes:
Locations:
city: Salzburg
country: Austria
facility: Paracelsus Medical University
city: Bad Krozingen
country: Germany
facility: University Heart Center Freiburg Bad Krozingen
city: Berlin
country: Germany
facility: German Heart Institute Berlin
city: Bonn
country: Germany
facility: University Hospital Bonn
city: Gießen
country: Germany
facility: University Hospital Gießen Marburg
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg
city: Homburg/Saar
country: Germany
facility: University Hospital Saarland
city: Leipzig
country: Germany
facility: University of Leipzig, Heart Center
city: Tübingen
country: Germany
facility: University Hospital Tübingen
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
city: Zürich
country: Switzerland
facility: University Hospital Zurich
Study officials:
affiliation: University Hospital, Saarland
name: Michael Böhm, MD
role: PRINCIPAL_INVESTIGATOR
References: