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).

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.

• Authors: Jose Antonio Marin-Neto, Anis Rassi Jr, Carlos A Morillo, Alvaro Avezum, Stuart J Connolly, Sergio Sosa-Estani, Fernando Rosas, Salim Yusuf, BENEFIT Investigators
• Journal: American heart journal (Am Heart J) Vol. 156 Issue 1 Pg. 37-43 (Jul 2008) ISSN: 1097-6744 [Electronic] United States
• PMID: 18585495 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Nitroimidazoles
• benzonidazole

Topics

• Chagas Cardiomyopathy (diagnosis, drug therapy, etiology, 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, diagnosis, drug therapy)