A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Antonio Luiz Pinho Ribeiro, Federal University of Minas Gerais
ClinicalTrials.gov Identifier:
NCT01557140
First received: February 21, 2012
Last updated: March 16, 2012
Last verified: March 2012

February 21, 2012
March 16, 2012
May 2003
March 2004   (final data collection date for primary outcome measure)
Changes in left ventricular ejection fraction [ Time Frame: Baseline, 4 months and 8 months ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01557140 on ClinicalTrials.gov Archive Site
  • Changes in Framingham score [ Time Frame: Baseline, 4 months and 8 months ] [ Designated as safety issue: No ]
  • Changes in quality of life (36-item Short-Form Health Survey) [ Time Frame: Baseline, 4 months and 8 months ] [ Designated as safety issue: No ]
  • Changes in New York Heart Association functional class [ Time Frame: Baseline, 4 months and 8 months ] [ Designated as safety issue: No ]
  • Changes in cardiothoracic ratio [ Time Frame: Baseline, 4 months and 8 months ] [ Designated as safety issue: No ]
  • Changes in echocardiographic diastolic function indices [ Time Frame: Baseline, 4 months and 8 months ] [ Designated as safety issue: No ]
  • Changes in brain natriuretic peptide levels [ Time Frame: Baseline, 4 months and 8 months ] [ Designated as safety issue: No ]
  • Changes in chemokines [ Time Frame: Baseline, 4 months and 8 months ] [ Designated as safety issue: No ]
  • Changes in autoantibodies levels [ Time Frame: Baseline, 4 months and 8 months ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Chagas Cardiomyopathy
  • Heart Failure
  • Dilated Cardiomyopathy
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:
  • Randomized
  • Double blind
  • Controlled
  • Trial
  • No Intervention: RASi plus placebo
    RAS inhibition was optimized and after patients were randomly assigned to receive placebo
  • No Intervention: RASi plus carvedilol
    RAS inhibition was optimized and after patients were randomly assigned to receive carvedilol
    Intervention: Drug: RASi plus carvedilol
Botoni FA, Poole-Wilson PA, Ribeiro AL, Okonko DO, Oliveira BM, Pinto AS, Teixeira MM, Teixeira AL Jr, Reis AM, Dantas JB, Ferreira CS, Tavares WC Jr, Rocha MO. A randomized trial of carvedilol after renin-angiotensin system inhibition in chronic Chagas cardiomyopathy. Am Heart J. 2007 Apr;153(4):544.e1-8.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
42
December 2006
March 2004   (final data collection date for primary outcome measure)

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).
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Brazil
 
NCT01557140
Carvedilol in Chagas disease
No
Antonio Luiz Pinho Ribeiro, Federal University of Minas Gerais
Federal University of Minas Gerais
Not Provided
Principal Investigator: Fernando A Botoni, MD, PhD Federal University of Minas Gerais
Federal University of Minas Gerais
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP