A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy

August 10, 2015 updated by: Antonio Luiz Pinho Ribeiro, Federal University of Minas Gerais

A Randomized Trial of Carvedilol After Renin-angiotensin System Inhibition in Chronic Chagas Cardiomyopathy

Chronic Chagas cardiomyopathy causes substantial morbidity and mortality in Latin America. Whether RAS inhibitors and beta-blockers are safe and beneficial has been challenged because of the lack of formal trials. Hence, the objective of this study was to determine the safety and efficacy of renin-angiotensin system (RAS) inhibitors and beta-blockers in chronic Chagas cardiomyopathy. This way, the investigators conducted a double-blind, placebo-controlled, and randomized trial in 42 patients with Trypanosoma cruzi infection and cardiomyopathy. All patients received enalapril (up-titrated to 20 mg BID) and spironolactone (25 mg QD). Subsequently, the patients were randomly assigned to receive placebo (n = 20) or carvedilol up-titrated to 25 mg BID (n = 19). The primary end points were change in left ventricular ejection fraction (LVEF) after RAS inhibition and that after the addition of carvedilol. The secondary end points were changes in other echocardiographic parameters, Framingham score, quality of life (36-item Short-Form Health Survey), New York Heart Association class, radiographic indices, brain natriuretic peptide levels, and chemokines as well as safety end points.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Chronic Chagas cardiomyopathy (CCC) is an important cause of heart failure (HF) and sudden death in Latin America.1 According to recent estimates, 13 million people worldwide are infected with Trypanosoma cruzi, of whom 3.0 to 3.3 million are symptomatic.2 The incidence rate is 200000 cases per year. Among those infected, 30% have clinical features of CCC and 15% ultimately develop overt left ventricular (LV) insufficiency-the main prognostic determinant of the disease. In Chagas cardiomyopathy, the hemodynamic and neurohormonal responses do not differ from those in other cardiomyopathies. This common pathophysiology suggests that treatments shown to be effective by classic HF trials should be beneficial in CCC. However, CCC has several specific characteristics, such as early cardiac denervation, frequent ventricular arrhythmias, and several forms as well as grades of conduction disturbances, including sinus bradycardia, complete atrioventricular block, and right bundle-branch block. Morphologically, hypertrophy, dilatation, and severe fibrosis are prominent. In 20% to 40% of cases, an apical ventricular aneurysm is present.1 These peculiarities in combination lead to a high incidence of sudden death (60% of all deaths), cardiac insufficiency, and ventricular remodeling. The responses of patients to the usual drugs prescribed in HF could be different, and this perception has led to the suboptimal dosing or lack of initiation of medical treatments that are of proven efficacy in patients with other etiologies of HF. The underlying problem is that therapies that are effective in patients with HF caused by non-chagasic cardiomyopathies, such as those with renin-angiotensin system inhibitors (RASis) and h-blockers, have yet to be formally tested in CCC. There are few clinical trials and no randomized study on this subject. Consequently, the investigators evaluated the effects of optimizing treatment with enalapril and spironolactone and then undertook a randomized trial of adding a h-blocker in the treatment of patients with CCC.

Study Type

Interventional

Enrollment (Actual)

42

Phase

  • Phase 4

Contacts and Locations

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

Study Locations

  • Brazil
    • Minas Gerais
      • Belo Horizonte, Minas Gerais, Brazil
        • Chagas Disease Outpatient Center of the Federal University of Minas Gerais

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 and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Criteria for inclusion were positivity for T cruzi as confirmed by 2 or more serological tests (indirect immunofluorescence, ELISA, and/or indirect hemagglutination) and having cardiomyopathy.

  • Cardiomyopathy was present when at least 3 of the following criteria were fulfilled:

    • LV enddiastolic diameter (LVDD) N55 mm
    • LVDD/body surface area > 2.7cm/m2
    • LV ejection fraction (LVEF) < 55%
    • QRS interval > 120 ms
    • echocardiographic evidence of diffuse or segmental systolic wall motion abnormalities.

Exclusion Criteria:

  • Exclusion criteria were being pregnant
  • Using any h-blocker
  • Having additional comorbidities (eg, hypertension, diabetes mellitus, thyroid dysfunction, chronic obstructive pulmonary disease, asthma, and renal or hepatic failure).

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
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: RASi plus placebo
RAS inhibition was optimized and after patients were randomly assigned to receive placebo
EXPERIMENTAL: RASi plus carvedilol
RAS inhibition was optimized and after patients were randomly assigned to receive carvedilol
Drug: RASi plus carvedilol
Patients were randomly assigned to 2 groups, with 1 group receiving renin-angiotensin system inhibitors (enalapril) plus carvedilol and the other receiving renin-angiotensin system inhibitors (enalapril) plus placebo
Other Names:
  • Controlled
  • Randomized
  • Double blind
  • Trial

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Changes in left ventricular ejection fraction
Time Frame: Baseline, 4 months and 8 months
Baseline, 4 months and 8 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Changes in Framingham score
Time Frame: Baseline, 4 months and 8 months
Baseline, 4 months and 8 months
Changes in quality of life (36-item Short-Form Health Survey)
Time Frame: Baseline, 4 months and 8 months
Baseline, 4 months and 8 months
Changes in New York Heart Association functional class
Time Frame: Baseline, 4 months and 8 months
Baseline, 4 months and 8 months
Changes in cardiothoracic ratio
Time Frame: Baseline, 4 months and 8 months
Baseline, 4 months and 8 months
Changes in echocardiographic diastolic function indices
Time Frame: Baseline, 4 months and 8 months
Baseline, 4 months and 8 months
Changes in brain natriuretic peptide levels
Time Frame: Baseline, 4 months and 8 months
Baseline, 4 months and 8 months
Changes in chemokines
Time Frame: Baseline, 4 months and 8 months
Baseline, 4 months and 8 months
Changes in autoantibodies levels
Time Frame: Baseline, 4 months and 8 months
Baseline, 4 months and 8 months

Collaborators and Investigators

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

Sponsor

Federal University of Minas Gerais

Investigators

  • Principal Investigator: Fernando A Botoni, MD, PhD, Federal University of Minas Gerais

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

May 1, 2003

Primary Completion (ACTUAL)

March 1, 2004

Study Completion (ACTUAL)

December 1, 2006

Study Registration Dates

First Submitted

February 21, 2012

First Submitted That Met QC Criteria

March 16, 2012

First Posted (ESTIMATE)

March 19, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

August 13, 2015

Last Update Submitted That Met QC Criteria

August 10, 2015

Last Verified

August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Carvedilol in Chagas disease

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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