Renal Denervation in Patients With Heart Failure and Severe Left Ventricular Dysfunction.

June 3, 2013 updated by: doc. MUDr. Miloš Táborský, CSc., FESC, MBA, University Hospital Olomouc

Long Term Study on the Possible Beneficial Effects of Catheterised Renal Denervation in Patients With Heart Failure and Left Ventricular Systolic Dysfunction Who Are Already on Standard Medical Therapy.

It is a randomized prospective controlled study evaluating the effect of transcatheter renal denervation on the clinical status of patients with chronic heart failure and its safety procedures. The working hypothesis of the study is that by performing transcatheter renal denervation in patients with chronic heart failure and severe left ventricular systolic dysfunction there will a resultant reduction in the renal sympathetic activation which in turn will reduce the number of hospitalizations and deaths from heart failure.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Chronic heart failure in the European countries occurs in 2-3% of the population with a significant increase in the higher age groups (1). Improved treatment of acute conditions (especially myocardial infarction) has resulted in more patients entering into the category of chronic heart failure. Chronic heart failure has a poor prognosis. Diagnosis and treatment are challenging both medically and economically. Half of the patients with systolic heart failure die within 4 years and more than 50% of patients with severe heart failure (NYHA functional class of IV) die within one year (1). The current treatments for heart failure are not only aimed at influencing the symptoms, but also preventing the progression of heart failure to reduce mortality.

Heart failure leads to the activation of compensatory mechanisms designed to restore adequate cardiac output. These mechanisms are initially beneficial, but their long-term activation leads to further progression of the pathological process and deterioration of cardiac function. One of the basic pathophysiological processes in heart failure is excessive activation of the sympathetic nervous system. This causes increased levels of circulating catecholamines which is proportional to the severity of the disease that is patients with the highest levels of norepinephrine have the worst prognosis. Beta-blocker therapy which is designed to inhibit activity of sympathetic nervous system causes milder symptoms of heart failure in patients by modifying disturbed hemodynamics and ultimately the clinical status. In recent years, the therapeutic efficacy of beta-blockers in chronic heart failure has been verified in a number of controlled clinical trials (2-5). These studies have confirmed that long-term treatment with beta-blocker therapy alleviates the symptoms of heart failure, improves the clinical condition of the patients and reduces mortality like ACE inhibitors.

High activity of renal sympathetic nerves in patients with chronic heart failure is an early predictor of increased mortality (6). The main pathophysiological basis of this finding is probably excessive sodium retention due to direct activation of sympathetic fibers innervating renal tubules (7). Recent experimental work on animals have shown that surgical renal denervation inhibits an increase in renal vascular resistance, prevents a decrease in renal blood flow (8), and also prevents changes in expression of angiotensin receptors in the kidney (8).

Surgical sympathectomy began to be used for the treatment of severe and malignant hypertension more than 50 years ago. But this was a rather complicated procedure, which was accompanied by a number of adverse effects (orthostatic hypotension and tachycardia, shortness of breath, bowel and sexual disorders]. Moreover it required a long hospitalization of 2-4 weeks and then required a recovery period of 1-2 months. However this intervention led to a rapid decrease in pressure and a higher survival rate after surgery in a large observational study(9).

In recent years a method has been developed in which destruction of renal sympathetic nerves that are present in the adventitia of renal arterial walls is done by catheterization (10). This procedure uses a catheter with a radiofrequency ablator at its tip (Symplicity, Ardian / Medtronic, USA), which is introduced through the femoral artery and then progressively introduced into the renal arteries. A randomized study has demonstrated that this procedure has a high degree of safety for the patients and a high rate of efficacy as well. In patients with resistant hypertension treated with transcatheter renal denervation there was a significant drop in blood pressure of 33/11 mmHg (p < 0.0001) that occurred after 6 months compared to a control group receiving unmodified pharmacological treatment (11).

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Czech Republic
      • Olomouc, Czech Republic, 775 20
        • Recruiting
        • University Hospital, Olomouc
        • Contact:
        • Contact:
          • Miloš Táborský, doc., MUDr., CSc., FESC, MBA
          • Phone Number: +420 588 443 201
          • Email: milos.taborsky@fnol.cz
        • Principal Investigator:
          • Miloš Táborský, doc., MUDr., CSc., FESC, MBA
        • Sub-Investigator:
          • Albert Louis, MUDr.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • Patients over 18 years of age with chronic heart failure, ischemic and non-ischemic etiology.
  • NYHA (New York Heart Association) class II-IV.
  • LVEF (Left Ventricular Ejection Fraction) ≤ 35%.
  • Patients treated with maximum tolerated doses of standard pharmacotherapy for heart failure, who were stable for at least four weeks without acute decompensated heart failure.
  • Prior to enrollment, patients must give informed consent.

Exclusion Criteria:

  • Patients with history of acute coronary syndrome or stroke within the last 6 months.
  • Significant valvular defects and/or planned cardiac surgery.
  • Systolic blood pressure <110 mmHg.
  • Advanced renal insufficiency (estimated GFR (Glomerular Filtration Rate) according to MDRD <30 ml/min/1.73 square meters).
  • Unsuitable anatomy of renal arteries (presence of significant renal stenosis, renal artery narrower than 4 mm).
  • Patients who underwent renal angioplasty or stent placement into the renal artery in the past.
  • Severe coagulation disorders.
  • Pregnancy or lactation.
  • Refusal of the patient.
  • Other diseases limiting prognosis of the patient to less than 2 years.
  • Other reasons which in the opinion of the attending physician would preclude the individual from participating in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Standard medical therapy
Experimental: Renal denervation + standard medical therapy
Patients in this arm will undergo catheterised renal denervation in addition to having optimization of medical therapy for heart failure.
Procedure: Catheterised renal denervation
Other Names:
  • Symplicity, Ardian / Medtronic, USA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in serum NT-proBNP at 6 months and 1 year from baseline in both groups.
Time Frame: 6 months and 1 year
The level of NT-proBNP (N-terminal prohormone of Brain Natriuretic Peptide) is a reliable indicator of the severity of heart failure. Lowering levels will indicate improvement in the heart function.
6 months and 1 year

Secondary Outcome Measures

Outcome Measure
Time Frame
Reduction in the number of hospitalizations and/or deaths due to cardiovascular causes.
Time Frame: 1 year to 4 years
1 year to 4 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Significant Renal impairment and symptomatic hypotension.
Time Frame: 6 months to 1 year
Increase in serum creatinine of 2 times the baseline or decrease in estimated glomerular filtration according to MDRD (Modification of Diet in Renal Disease) by more than 50% from baseline will be used to assess renal function.
6 months to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Olomouc

Investigators

  • Principal Investigator: Miloš Táborský, doc., MUDr., CSc., FESC, MBA, Head of Department of First Clinic of Internal Medicine - Cardiology, University Hospital, Olomouc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2012

Primary Completion (Anticipated)

September 1, 2013

Study Completion (Anticipated)

June 1, 2016

Study Registration Dates

First Submitted

May 25, 2013

First Submitted That Met QC Criteria

June 3, 2013

First Posted (Estimate)

June 6, 2013

Study Record Updates

Last Update Posted (Estimate)

June 6, 2013

Last Update Submitted That Met QC Criteria

June 3, 2013

Last Verified

June 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OLOMOUC 1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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