Renal Denervation in Patients With Heart Failure Secondary to Chagas Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by InCor Heart Institute
Sponsor:
Collaborator:
Johnson & Johnson
Information provided by (Responsible Party):
Pedro A. Lemos, InCor Heart Institute
ClinicalTrials.gov Identifier:
NCT02099903
First received: March 19, 2014
Last updated: March 26, 2014
Last verified: March 2014
  Purpose

It is a randomized prospective controlled study of transcatheter renal denervation in patients with systolic heart failure secondary to Chagas' disease. The purpose of the study is to evaluate the safety and effectiveness of renal denervation in patients with Chagas heart disease, due to reduction in renal and systemic sympathetic activity.


Condition Intervention
Heart Failure
Heart Failure, Systolic
Chagas Disease
Chagas Cardiomyopathy
Device: transcatheter renal denervation

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Transcatheter Renal Denervation in Patients With Systolic Heart Failure Due to Chagas' Disease - a Safety and Efficacy Study.

Resource links provided by NLM:


Further study details as provided by InCor Heart Institute:

Primary Outcome Measures:
  • Composite: death, myocardial infarction, cerebrovascular event, need of intervention on renal arteries and renal function impairment (decrease in estimated GFR > 30% from baseline). [ Time Frame: 30 days. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Left Ventricular Ejection Fraction (LVEF) by echocardiography. [ Time Frame: 9 months. ] [ Designated as safety issue: No ]
  • New York Heart Association (NYHA) functional class. [ Time Frame: 9 months. ] [ Designated as safety issue: No ]
  • 6-minute walk test [ Time Frame: 9 months. ] [ Designated as safety issue: No ]
  • Peak Oxygen consumption (VO2) by ergoespirometry. [ Time Frame: 9 months. ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Change in serum B-type natriuretic peptide (BNP). [ Time Frame: 9 months. ] [ Designated as safety issue: No ]
  • Quality of life assessed by Minnesota and EuroQOL five dimensions (EQ-5D)questionnaires. [ Time Frame: 9 months. ] [ Designated as safety issue: No ]
  • Peripheral sympathetic activity measured by microneurography. [ Time Frame: 9 months. ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: March 2014
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Medical therapy for heart failure
Standard optimized medical therapy for heart failure.
Experimental: Renal denervation + medical therapy.
Transcatheter Renal Denervation with irrigated radiofrequency catheter + standard medical therapy.
Device: transcatheter renal denervation
Renal sympathetic denervation with an irrigated radiofrequency catheter.
Other Name: Celsius Thermocool (Biosense Webster, California, USA)

Detailed Description:

The activation of the sympathetic nervous system is one of the main mechanisms involved in heart failure pathophysiology, as well as activation of the renin-angiotensin-aldosterone system. These compensatory mechanisms are initially beneficial, in order to restore adequate cardiac output. Their long-term activation, nevertheless, leads to several deleterious effects on cardiovascular system, such as direct myocite lesion, cardiac hypertrophy, myocardial ischemia, oxidative stress, cardiac arrhythmias and myocite apoptosis, among others.

It has been widely demonstrated that modulation of sympathetic nervous system is an important therapeutic target for the treatment of systolic heart failure. Beta-blocker and ACE inhibitors therapies are the main stem of heart failure treatment and have demonstrated reduction in morbidity and mortality of this condition. Despite optimized medical treatment, heart failure carries a poor prognosis.

Surgical sympathectomy has been used decades ago for the treatment of malignant hypertension and showed marked reduction in arterial pressure. However, these procedures were very aggressive and lead to long hospitalization and recovery periods, as well as several limiting adverse effects. Recently, transcatheter renal denervation has evolved as a promising and less invasive technique, which allows destruction of renal nerves located on the adventitia of the renal arteries. The ablation procedure is performed by delivery of radiofrequency energy from the tip of a catheter positioned into the renal arteries, through standard femoral artery catheterization, a less morbid and safer approach.

Renal denervation has been tested mainly in patients with resistant hypertension, among other indications, with promising results. The pathophysiological basis for this treatment in hypertension, as well as heart failure, stands on the participation of renal afferent and efferent nerves on the maintenance of elevated systemic vascular resistance. Activation of efferent nerves leads to excretion o renin, aldosterone, angiotensin II, elevated norepinephrine levels and consequent retention of salt and water and reduction of renal blood flow. This mechanism and also afferent renal nerves activation contributes to the elevation of sympathetic tonus on the central nervous system.

In animal models of heart failure, renal denervation demonstrated improvement on renal and cardiac function. Initial clinical studies suggest that this intervention is safe and potentially effective on the treatment of heart failure in humans. Chagas heart disease is a prevalent cause of heart failure in Brazil and shares several pathophysiological aspects described for other causes of heart failure. Our aim is to evaluate the safety and effectiveness of renal denervation in systolic heart failure due to Chagas Heart disease.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients ≥ 18 to ≤ 70 years of age with chronic systolic heart failure, Chagas disease etiology.
  2. Two positive serology results for Chagas by two distinct methods.
  3. NYHA (New York Heart Association) class II or III.
  4. Patients treated with maximum tolerated doses of standard pharmacotherapy for heart failure.
  5. LVEF (Left Ventricular Ejection Fraction) ≤ 40% (Simpson Method).

Exclusion Criteria:

  1. Patients with NYHA class I or IV.
  2. Sustained ventricular tachycardia (>30 sec) or with hemodynamic compromise.
  3. Presence of permanent pacemaker or implantable defibrillator.
  4. Systolic blood pressure < 90 mmHg.
  5. Heart beat < 60 bpm at rest.
  6. Advanced renal insufficiency (estimated glomerular filtration rate (GFR) < 30 ml/min/1.73 square meters).
  7. Patients with planned cardiac surgery or percutaneous revascularization.
  8. Other reasons which would preclude the patient from participating in the study (comorbidities, life expectancy less than 1 year).
  9. Unsuitable anatomy of renal arteries, renal stenosis or previous treatment with balloon or stent.
  10. Refusal of the patient.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02099903

Locations
Brazil
Heart Institute - InCor. University of Sao Paulo Medical School Recruiting
Sao Paulo, Brazil, 05403-000
Contact: Patricia Pereira    +55 11 2661-5368    patricia.pereira@incor.usp.br   
Principal Investigator: Pedro Lemos, MD PhD         
Sponsors and Collaborators
InCor Heart Institute
Johnson & Johnson
  More Information

No publications provided

Responsible Party: Pedro A. Lemos, Professor of Medicine, InCor Heart Institute
ClinicalTrials.gov Identifier: NCT02099903     History of Changes
Other Study ID Numbers: 18400613.1.0000.0068
Study First Received: March 19, 2014
Last Updated: March 26, 2014
Health Authority: Brazil: Ethics Committee
Brazil: National Committee of Ethics in Research

Keywords provided by InCor Heart Institute:
Heart Failure
Heart Failure, Systolic
Chagas Disease
Chagas Cardiomyopathy
Renal Denervation
Irrigated Radiofrequency Catheter

Additional relevant MeSH terms:
Heart Failure
Heart Failure, Systolic
Chagas Cardiomyopathy
Chagas Disease
Cardiomyopathies
Trypanosomiasis
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on August 19, 2014