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A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy

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ClinicalTrials.gov Identifier: NCT01557140
Recruitment Status : Completed
First Posted : March 19, 2012
Last Update Posted : August 13, 2015
Sponsor:
Information provided by (Responsible Party):
Antonio Luiz Pinho Ribeiro, Federal University of Minas Gerais

Tracking Information
First Submitted Date  ICMJE February 21, 2012
First Posted Date  ICMJE March 19, 2012
Last Update Posted Date August 13, 2015
Study Start Date  ICMJE May 2003
Actual Primary Completion Date March 2004   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 16, 2012)
Changes in left ventricular ejection fraction [ Time Frame: Baseline, 4 months and 8 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01557140 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 16, 2012)
  • Changes in Framingham score [ Time Frame: 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 ]
  • Changes in New York Heart Association functional class [ Time Frame: Baseline, 4 months and 8 months ]
  • Changes in cardiothoracic ratio [ Time Frame: Baseline, 4 months and 8 months ]
  • Changes in echocardiographic diastolic function indices [ Time Frame: Baseline, 4 months and 8 months ]
  • Changes in brain natriuretic peptide levels [ Time Frame: Baseline, 4 months and 8 months ]
  • Changes in chemokines [ Time Frame: Baseline, 4 months and 8 months ]
  • Changes in autoantibodies levels [ Time Frame: Baseline, 4 months and 8 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
Official Title  ICMJE 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Chagas Cardiomyopathy
  • Heart Failure
  • Dilated Cardiomyopathy
Intervention  ICMJE 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
Study Arms  ICMJE
  • 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
    Intervention: Drug: RASi plus carvedilol
Publications * 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.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 16, 2012)
42
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2006
Actual Primary Completion Date March 2004   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01557140
Other Study ID Numbers  ICMJE Carvedilol in Chagas disease
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Antonio Luiz Pinho Ribeiro, Federal University of Minas Gerais
Study Sponsor  ICMJE Federal University of Minas Gerais
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Fernando A Botoni, MD, PhD Federal University of Minas Gerais
PRS Account Federal University of Minas Gerais
Verification Date August 2015

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