Rationale and Design of a Randomized Placebo-Controlled Trial Assessing the Effects of Etiologic Treatment in Chagas' Cardiomyopathy: The BENznidazole Evaluation For Interrupting Trypanosomiasis (BENEFIT)

Am Heart J. 2008 Jul;156(1):37-43. doi: 10.1016/j.ahj.2008.04.001.

Abstract

Background: Benznidazole is effective for treating acute and chronic (recently acquired) Trypanosoma cruzi infection (Chagas' disease). Recent data indicate that parasite persistence plays a pivotal role in the pathogenesis of chronic Chagas' cardiomyopathy. However, the efficacy of trypanocidal therapy in preventing clinical complications in patients with preexisting cardiac disease is unknown.

Study design: BENEFIT is a multicenter, randomized, double-blind, placebo-controlled clinical trial of 3,000 patients with Chagas' cardiomyopathy in Latin America. Patients are randomized to receive benznidazole (5 mg/kg per day) or matched placebo, for 60 days. The primary outcome is the composite of death; resuscitated cardiac arrest; sustained ventricular tachycardia; insertion of pacemaker or cardiac defibrillator; cardiac transplantation; and development of new heart failure, stroke, or systemic or pulmonary thromboembolic events. The average follow-up time will be 5 years, and the trial has a 90% power to detect a 25% relative risk reduction. The BENEFIT program also comprises a substudy evaluating the effects of benznidazole on parasite clearance and an echo substudy exploring the impact of etiologic treatment on left ventricular function. Recruitment started in November 2004, and >1,000 patients have been enrolled in 35 centers from Argentina, Brazil, and Colombia to date.

Conclusion: This is the largest trial yet conducted in Chagas' disease. BENEFIT will clarify the role of trypanocidal therapy in preventing cardiac disease progression and death.

Trial registration: ClinicalTrials.gov NCT00123916.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chagas Cardiomyopathy / diagnosis
  • Chagas Cardiomyopathy / drug therapy*
  • Chagas Cardiomyopathy / etiology*
  • Chagas Cardiomyopathy / mortality
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Evaluation Studies as Topic
  • Female
  • Follow-Up Studies
  • Humans
  • Latin America
  • Male
  • Nitroimidazoles / therapeutic use*
  • Pilot Projects
  • Risk Assessment
  • Severity of Illness Index
  • Survival Analysis
  • Time Factors
  • Treatment Outcome
  • Trypanosomiasis / complications*
  • Trypanosomiasis / diagnosis
  • Trypanosomiasis / drug therapy*

Substances

  • Nitroimidazoles
  • benzonidazole

Associated data

  • ClinicalTrials.gov/NCT00123916
  • ISRCTN/ISRCTN13967269