Brief Title
A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
Official Title
A Randomized Trial of Carvedilol After Renin-angiotensin System Inhibition in Chronic Chagas Cardiomyopathy
Brief Summary
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.
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 Phase
Phase 4
Study Type
Interventional
Primary Outcome
Changes in left ventricular ejection fraction
Secondary Outcome
Changes in Framingham score
Condition
Chagas Cardiomyopathy
Intervention
RASi plus carvedilol
Study Arms / Comparison Groups
RASi plus placebo
Description: RAS inhibition was optimized and after patients were randomly assigned to receive placebo
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
42
Start Date
May 2003
Completion Date
December 2006
Primary Completion Date
March 2004
Eligibility Criteria
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).
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Fernando A Botoni, MD, PhD, ,
Location Countries
Brazil
Location Countries
Brazil
Administrative Informations
NCT ID
NCT01557140
Organization ID
Carvedilol in Chagas disease
Responsible Party
Principal Investigator
Study Sponsor
Federal University of Minas Gerais
Study Sponsor
Fernando A Botoni, MD, PhD, Principal Investigator, Federal University of Minas Gerais
Verification Date
August 2015