A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy

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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