Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial.
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.


METHODS
Clinical trial with unblinded, nonrandom assignment of patients to intervention or control groups.


METHODS
Chagas disease center in Buenos Aires, Argentina.


METHODS
566 patients 30 to 50 years of age with 3 positive results on serologic tests and without heart failure.


METHODS
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.


METHODS
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).


CONCLUSIONS
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.
Viotti
Rodolfo
R
Hospital Interzonal General de Agudos Eva Perón and Instituto Nacional de Parasitología Dr. Mario Fatala Chaben, Buenos Aires, Argentina. peron@millicom.com.ar
Vigliano
Carlos
C
Lococo
Bruno
B
Bertocchi
Graciela
G
Petti
Marcos
M
Alvarez
María Gabriela
MG
Postan
Miriam
M
Armenti
Alejandro
A
D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D002598:Chagas Cardiomyopathy / Q000175:diagnosis* / Q000209:etiology; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology / Q000503:physiopathology; D002908:Chronic Disease; D018450:Disease Progression; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009593:Nitroimidazoles / Q000627:therapeutic use*; D011379:Prognosis; D012680:Sensitivity and Specificity; D014344:Trypanocidal Agents / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000276:immunology
D000913:Antibodies, Protozoan; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C009999:benzonidazole