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Benznidazole more effective than posaconazole at treating T. cruzi infection in asymptomatic patients
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CHICAGO — Benznidazole monotherapy or benznidazole combined with posaconazole is more effective at treating Trypanosoma cruzi infection in asymptomatic patients than posaconazole alone, according to data presented at the American College of Cardiology Scientific Session.
However, there are significant adverse effects with benznidazole, researchers reported.
“Approximately 8 million people are chronically affected with T. cruzi and 30% of infected individuals may develop cardiomyopathy in 30 years,” Carlos Morillo, MD, FRCP(C), FACC, from the Population Health Research Institute and McMaster University in Hamilton, Ontario, Canada, said during a presentation. “However, the vast majority of these individuals have what we would call an indeterminate form of the disease. That is, there is no evidence of cardiac myopathy or any electrographic evidence of cardiac alterations.”
STOP-CHAGAS is a multicenter, randomized, four-arm study that evaluated the short- and long-term effects of benznidazole monotherapy, posaconazole monotherapy (Noxafil, Merck) and combined therapy compared with placebo. The trial was conducted in 17 centers in Argentina, Chile, Colombia, Guatemala, Mexico and Spain. For eligibility, patients were required to be aged 18 to 50 years and have at least two positive serologic tests and a positive polymerase chain reaction (PCR) test detecting T. cruzi DNA.
Overall, 120 patients were enrolled in the study with 30 patients randomly assigned to each arm:
- posaconazole 400 mg twice daily;
- placebo 10 mL twice daily;
- benznidazole 200 mg twice daily plus posaconazole 400 mg twice daily; or
- benznidazole 200 mg twice daily plus placebo twice daily.
The primary endpoint was the proportion of patients with persistent negative PCR at 180 days. Mean follow-up was 360 days.
According to the results, patients in the posaconazole or combination therapy groups, as well as the benznidazole monotherapy group, had higher rates of negative PCR at day 30 and day 60 (posaconazole, 91%; combination therapy, 92%; benznidazole, 92%) than those in the placebo group (10%; P < .001). However, at 180 days, the rate of negative PCR in the posaconazole group was only 15.5% (95% CI, 6.9-31.8), comparable to the rate in the placebo group (10%; 95% CI, 3.5-25.6). In contrast, the rates were 82.1% (95% CI, 64.4-92.1) for the combined therapy group and 86.7% (95% CI, 70.3-94.7) for the benznidazole monotherapy group (P < .0001 for all comparisons of combination therapy or benznidazole vs. posaconazole or placebo).
Posaconazole achieved results in the short term that were not sustained long term, while benznidazole was effective in both the short and long term, Morillo said during the presentation. However, he said, 30% of those assigned benznidazole, alone or in a combined therapy, had to discontinue therapy due to adverse effects.
“The problem with benznidazole is that there is a significant amount of side effects. The effectiveness of a shorter duration of treatment with a lower dose along with the combination therapy should be investigated further,” Morillo said. – by Tracey Romero
Reference:
Morillo C, et. al. Featured Clinical Research II. Presented at: American College of Cardiology Scientific Session; April 2-4, 2016; Chicago.
Disclosure: The STOP-CHAGAS trial was funded by Merck. Morillo reports no relevant financial disclosures.