Background: Benznidazole is effective for treating acute-stage Chagas disease, but its effectiveness for treating indeterminate and chronic stages remains uncertain.
Objective: To compare long-term outcomes of patients with nonacute Chagas disease treated with benznidazole versus outcomes of those who did not receive treatment.
Design: Clinical trial with unblinded, nonrandom assignment of patients to intervention or control groups.
Setting: Chagas disease center in Buenos Aires, Argentina.
Patients: 566 patients 30 to 50 years of age with 3 positive results on serologic tests and without heart failure.
Measurements: The primary outcome was disease progression, defined as a change to a more advanced Kuschnir group or death. Secondary outcomes included new abnormalities on electrocardiography and serologic reactivity.
Intervention: Oral benznidazole, 5 mg/kg of body weight per day for 30 days (283 patients), or no treatment (283 patients).
Results: Fewer treated patients had progression of disease (12 of 283 [4%] vs. 40 of 283 [14%]; adjusted hazard ratio, 0.24 [95% CI, 0.10 to 0.59]; P = 0.002) or developed abnormalities on electrocardiography (15 of 283 [5%] vs. 45 of 283 [16%]; adjusted hazard ratio, 0.27 [CI, 0.13 to 0.57]; P = 0.001) compared with untreated patients. Left ventricular ejection fraction (hazard ratio, 0.97 [CI, 0.94 to 0.99]; P < 0.002) and left ventricular diastolic diameter (hazard ratio, 2.45 [CI, 1.53 to 3.95]; P < 0.001) were also associated with disease progression. Conversion to negative results on serologic testing was more frequent in treated patients than in untreated patients (32 of 218 [15%] vs. 12 of 212 [6%]; adjusted hazard ratio, 2.1 [CI, 1.06 to 4.06]; P = 0.034).
Limitations: Nonrandom, unblinded treatment assignment was used, and follow-up data were missing for 20% of patients. Loss to follow-up was more common among patients who were less sick. Two uncontrolled interim analyses were conducted.
Conclusions: Compared with no treatment, benznidazole treatment was associated with reduced progression of Chagas disease and increased negative seroconversion for patients presenting with nonacute disease and no heart failure. These observations indicate that a randomized, controlled trial should now be conducted.