Renal Denervation in Patients With Heart Failure Secondary to Chagas Disease

Heart Failure Clinical Trial

Official title:

Transcatheter Renal Denervation in Patients With Systolic Heart Failure Due to Chagas' Disease - a Safety and Efficacy Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02099903
• Other study ID #: 18400613.1.0000.0068
• Status: Recruiting
• Phase: N/A
• First received: March 19, 2014
• Last updated: March 26, 2014
• Start date: March 2014
• Est. completion date: August 2015

Study information

• Verified date: March 2014
• Source: InCor Heart Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics CommitteeBrazil: National Committee of Ethics in Research
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: August 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiomyopathies
• Chagas Cardiomyopathy
• Chagas Disease
• Heart Failure
• Heart Failure, Systolic

Intervention

Device:
• transcatheter renal denervation
Renal sympathetic denervation with an irrigated radiofrequency catheter.

Locations

Country	Name	City	State
Brazil	Heart Institute - InCor. University of Sao Paulo Medical School	Sao Paulo

Sponsors (2)

Lead Sponsor	Collaborator
InCor Heart Institute	Johnson & Johnson

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in serum B-type natriuretic peptide (BNP).		9 months.	No
Other	Quality of life assessed by Minnesota and EuroQOL five dimensions (EQ-5D)questionnaires.		9 months.	No
Other	Peripheral sympathetic activity measured by microneurography.		9 months.	No
Primary	Composite: death, myocardial infarction, cerebrovascular event, need of intervention on renal arteries and renal function impairment (decrease in estimated GFR > 30% from baseline).		30 days.	Yes
Secondary	Left Ventricular Ejection Fraction (LVEF) by echocardiography.		9 months.	No
Secondary	New York Heart Association (NYHA) functional class.		9 months.	No
Secondary	6-minute walk test		9 months.	No
Secondary	Peak Oxygen consumption (VO2) by ergoespirometry.		9 months.	No