Randomized Trial of Benznidazole for Chronic Chagas' Cardiomyopathy

• Autores: Morillo, C. A.; Marin Neto, J. A.; Avezum, Alvaro; Sosa-Estani, Sergio Alejandro; Rassi Junior, A.; Rosas, F.; Villena, E.; Quiroz, R.; Bonilla, R.; Britto, C.; Guhl, F.; Velazquez, E.; Bonilla, L.; Meeks, B.; Rao Melacini, P.; Pogue, J.; Mattos, A.; Lazdins, J.; Rassi, A.; Connolly, S. J.; Yusuf, S.
• Año de publicación: 2015
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Chagas; Trypanosoma Cruzi; Benznidazole; Clinical Trial
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

BACKGROUND:The role of trypanocidal therapy in patients with established Chagas´ cardiomyopathy is unproven.METHODS:We conducted a prospective, multicenter, randomized study involving 2854 patients with Chagas´ cardiomyopathy who received benznidazole or placebo for up to 80 days and were followed for a mean of 5.4 years. The primary outcome in the time-to-event analysis was the first event of any of the components of the composite outcome of death, resuscitated cardiac arrest, sustained ventricular tachycardia, insertion of a pacemaker or implantable cardioverter-defibrillator, cardiac transplantation, new heart failure, stroke, or other thromboembolic event.RESULTS:The primary outcome occurred in 394 patients (27.5%) in the benznidazole group and in 414 (29.1%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.07; P=0.31). At baseline, a polymerase-chain-reaction (PCR) assay was performed on blood samples obtained from 1896 patients; 60.5% had positive results for Trypanosoma cruzi on PCR. The rates of conversion to negative PCR results (PCR conversion) were 66.2% in the benznidazole group and 33.5% in the placebo group at the end of treatment, 55.4% and 35.3%, respectively, at 2 years, and 46.7% and 33.1%, respectively, at 5 years or more (P<0.001 for all comparisons). The effect of treatment on PCR conversion varied according to geographic region: in Brazil, the odds ratio for PCR conversion was 3.03 (95% CI, 2.12 to 4.34) at 2 years and 1.87 (95% CI, 1.33 to 2.63) at 5 or more years; in Colombia and El Salvador, the odds ratio was 1.33 (95% CI, 0.90 to 1.98) at 2 years and 0.96 (95% CI, 0.63 to 1.45) at 5 or more years; and in Argentina and Bolivia, the odds ratio was 2.63 (95% CI, 1.89 to 3.66) at 2 years and 2.79 (95% CI, 1.99 to 3.92) at 5 or more years (P<0.001 for interaction). However, the rates of PCR conversion did not correspond to effects on clinical outcome (P=0.16 for interaction).CONCLUSIONS:Trypanocidal therapy with benznidazole in patients with established Chagas´ cardiomyopathy significantly reduced serum parasite detection but did not significantly reduce cardiac clinical deterioration through 5 years of follow-up. (Funded by the Population Health Research Institute and others; ClinicalTrials.gov number, NCT00123916; Current Controlled Trials number, ISRCTN13967269.).
Fil: Morillo, C. A.. No especifica;
Fil: Marin Neto, J. A.. No especifica;
Fil: Avezum, Alvaro. No especifica;
Fil: Sosa-Estani, Sergio Alejandro. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Centro Nacional de Diagnóstico e Investigaciones Endemo-epidémicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rassi Junior, A.. No especifica;
Fil: Rosas, F.. No especifica;
Fil: Villena, E.. No especifica;
Fil: Quiroz, R.. No especifica;
Fil: Bonilla, R.. No especifica;
Fil: Britto, C.. No especifica;
Fil: Guhl, F.. No especifica;
Fil: Velazquez, E.. No especifica;
Fil: Bonilla, L.. No especifica;
Fil: Meeks, B.. No especifica;
Fil: Rao Melacini, P.. No especifica;
Fil: Pogue, J.. No especifica;
Fil: Mattos, A.. No especifica;
Fil: Lazdins, J.. No especifica;
Fil: Rassi, A.. No especifica;
Fil: Connolly, S. J.. No especifica;
Fil: Yusuf, S.. No especifica;