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).
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.


METHODS
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.


CONCLUSIONS
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.
Marin-Neto
Jose Antonio
JA
Medical School of Ribeirao Preto, University of Sao Paulo, Ribeirão Preto, Sao Paulo, Brazil. marin_neto@yahoo.com
Rassi
Anis
A
Morillo
Carlos A
CA
Avezum
Alvaro
A
Connolly
Stuart J
SJ
Sosa-Estani
Sergio
S
Rosas
Fernando
F
Yusuf
Salim
S
D002598:Chagas Cardiomyopathy / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology* / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005069:Evaluation Studies as Topic; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007843:Latin America; D008297:Male; D009593:Nitroimidazoles / Q000627:therapeutic use*; D010865:Pilot Projects; D018570:Risk Assessment; D012720:Severity of Illness Index; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D014352:Trypanosomiasis / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy*
D009593:Nitroimidazoles; C009999:benzonidazole