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A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01557140
Recruitment Status : Completed
First Posted : March 19, 2012
Last Update Posted : August 13, 2015
Information provided by (Responsible Party):
Antonio Luiz Pinho Ribeiro, Federal University of Minas Gerais

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.

Condition or disease Intervention/treatment Phase
Chagas Cardiomyopathy Heart Failure Dilated Cardiomyopathy Drug: RASi plus carvedilol Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Trial of Carvedilol After Renin-angiotensin System Inhibition in Chronic Chagas Cardiomyopathy
Study Start Date : May 2003
Actual Primary Completion Date : March 2004
Actual Study Completion Date : December 2006

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:
  • Randomized
  • Double blind
  • Controlled
  • Trial

Primary Outcome Measures :
  1. Changes in left ventricular ejection fraction [ Time Frame: Baseline, 4 months and 8 months ]

Secondary Outcome Measures :
  1. Changes in Framingham score [ Time Frame: Baseline, 4 months and 8 months ]
  2. Changes in quality of life (36-item Short-Form Health Survey) [ Time Frame: Baseline, 4 months and 8 months ]
  3. Changes in New York Heart Association functional class [ Time Frame: Baseline, 4 months and 8 months ]
  4. Changes in cardiothoracic ratio [ Time Frame: Baseline, 4 months and 8 months ]
  5. Changes in echocardiographic diastolic function indices [ Time Frame: Baseline, 4 months and 8 months ]
  6. Changes in brain natriuretic peptide levels [ Time Frame: Baseline, 4 months and 8 months ]
  7. Changes in chemokines [ Time Frame: Baseline, 4 months and 8 months ]
  8. Changes in autoantibodies levels [ Time Frame: Baseline, 4 months and 8 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01557140

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Chagas Disease Outpatient Center of the Federal University of Minas Gerais
Belo Horizonte, Minas Gerais, Brazil
Sponsors and Collaborators
Federal University of Minas Gerais
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Principal Investigator: Fernando A Botoni, MD, PhD Federal University of Minas Gerais

Publications of Results:
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Responsible Party: Antonio Luiz Pinho Ribeiro, Director-General, Hospital das Clínicas, UFMG, Federal University of Minas Gerais Identifier: NCT01557140    
Other Study ID Numbers: Carvedilol in Chagas disease
First Posted: March 19, 2012    Key Record Dates
Last Update Posted: August 13, 2015
Last Verified: August 2015
Keywords provided by Antonio Luiz Pinho Ribeiro, Federal University of Minas Gerais:
Chagas cardiomyopathy,
Renin-angiotensin system,
Renin-angiotensin system inhibitors,
Brain natriuretic peptide level,
Left ventricular ejection fraction,
Additional relevant MeSH terms:
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Chagas Cardiomyopathy
Cardiomyopathy, Dilated
Heart Diseases
Cardiovascular Diseases
Chagas Disease
Euglenozoa Infections
Protozoan Infections
Parasitic Diseases
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Antihypertensive Agents
Protective Agents
Calcium Channel Blockers
Membrane Transport Modulators
Calcium-Regulating Hormones and Agents
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors