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)

MARIN-NETO JA, RASSI A JR, MORILLO CA, AVEZUM A, CONNOLLY SJ, SOSA-ESTANI S, ROSAS F, YUSUF S; BENEFIT INVESTIGATORS

AMERICAN HEART JOURNAL, THE

MOSBY-ELSEVIER

Año: 2008 vol. 156 p. 37 - 43

0002-8703

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.