Document Detail


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).
MedLine Citation:
PMID:  18585495     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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; Carlos A Morillo; Alvaro Avezum; Stuart J Connolly; Sergio Sosa-Estani; Fernando Rosas; Salim Yusuf;
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Publication Detail:
Type:  Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American heart journal     Volume:  156     ISSN:  1097-6744     ISO Abbreviation:  Am. Heart J.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-30     Completed Date:  2008-07-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370465     Medline TA:  Am Heart J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  37-43     Citation Subset:  AIM; IM    
Affiliation:
Medical School of Ribeirao Preto, University of Sao Paulo, Ribeirão Preto, Sao Paulo, Brazil. marin_neto@yahoo.com
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00123916; ISRCTN/ISRCTN13967269
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MeSH Terms
Descriptor/Qualifier:
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*
Chemical
Reg. No./Substance:
0/Nitroimidazoles; 22994-85-0/benzonidazole
Investigator
Investigator/Affiliation:
S Yusuf / ; J A Marin-Neto / ; C A Morillo / ; A Rassi / ; A Rassi / ; A Avezum / ; S J Connolly / ; S Sosa-Estani / ; F Rosas / ; C Britto / ; J Lazdins / ; B Ramos / ; C Morillo / ; A Avezum / ; S Yusuf / ; J A Marin-Neto / ; R Oliveira / ; L Dyal / ; H Penna-Guimarães / ; A C Mattos / ; A Rassi / ; C Britto / ; S Sosa-Estani / ; E Segura / ; F Rosas / ; F Guhl / ; J Lazdins / ; B C Maciel / ; P Sleight / ; H Acquatella / ; J Lazzari / ; D Sackett / ; R Robins / ; C Morillo / ; S Yusuf / ; B Ramos / ; R Oliveira / ; A Avezum / ; H Penna-Guimaraes / ; A C Mattos / ; J R Zappiello-Mendes / ; Juarez Braga / ; J A Marin-Neto / ; B C BC Maciel / ; Tonani / ; S Sosa-Estani / ; T A Orduna / ; F A Silva-Nieto / ; M P Bernachea / ; R Carrizo Pae / ; R Manzur / ; C A Cuneo / ; G Perez-Pardos / ; J Beloscar / ; E Oshiro / ; M C Bangher / ; L Gomes / ; V I Volberg / ; M Mallagray / ; A Rassi Jr / ; A Luquetti / ; A Schmidt / ; A A Fragata Filho / ; L Nigro-Maia / ; A M L Lorga / ; A S Souza / ; R C Pedrosa / ; E D Gontijo / ; W A Oliveira Jr / ; R Aras / ; G S Feitosa / ; A Prata / ; T L Silva / ; A A Steffens / ; C L P Cunha / ; L F A Oliveira / ; A C Carvalho / ; A C A Souza / ; J F K Saraiva / ; C Mady / ; E A Bocchi / ; G Reis / ; A A Fagundes / ; F Rosas / ; S Navarrete / ; R Quiroz / ; R Onate / ; E Villena / ; B Arana / ; A Laguna / ; R Espinosa /

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