Benznidazole and Posaconazole in Eliminating Parasites in T. Cruzi Carriers

Study Questions:

What are the effects of combination therapy with benznidazole and posaconazole in T. cruzi carriers?

Methods:

STOP-CHAGAS was a prospective, multicenter, randomized, placebo-controlled study conducted in 120 subjects from Latin America and Spain who were randomized to four groups: posaconazole 400 mg twice a day (bid), benznidazole 200 mg plus placebo bid, benznidazole 200 mg bid plus posaconazole 400 mg bid, or placebo 10 mg bid. T. Cruzi DNA was detected by real-time polymerase chain reaction (RT-PCR) at 30, 60, 90, 120, 150, 180, and 360 days. The primary efficacy outcome was the proportion of subjects with persistent negative RT-PCR by day 180; the secondary outcome was negative RT-PCR at 360 days.

Results:

Only 13.3% of those receiving posaconazole and 10% receiving placebo achieved the primary outcome, compared with 80% receiving benznidazole + posaconazole and 86.7% receiving benznidazole monotherapy (p < 0.0001 vs. posaconazole/placebo). Posaconazole monotherapy or combined with benznidazole achieved high RT-PCR conversion rates during treatment (30 days, 93.3% and 88.9%; and 60 days, 90% and 92.3%) that were similar to benznidazole (89.7% and 89.3%); all superior to placebo or posaconazole (10% and 16.7%, p < 0.0001). This was not observed at 360 days; benznidazole + posaconazole and benznidazole monotherapy (both 96%), versus placebo (17%) and posaconazole (16%, p < 0.0001). Serious adverse events were rare (six patients), and observed in the benznidazole-treated patients. Permanent discontinuation was reported in 19 patients (31.7%) receiving either benznidazole monotherapy or combined with posaconazole.

Conclusions:

The authors concluded that no advantages were observed with combined therapy compared to benznidazole monotherapy.

Perspective:

This study reports that among individuals with chronic asymptomatic T. cruzi infection, posaconazole had significant short-term trypanostatic therapy; however, this effect was not sustained. Monotherapy with benznidazole was superior to posaconazole monotherapy, and achieved conversion of T. cruzi in all subjects on treatment by 30 days, which was sustained for at least 1 year. Furthermore, combination therapy did not provide any further advantages compared to benznidazole monotherapy. Additional research is indicated to mitigate the side effects of benznidazole, which resulted in discontinuation in one-third of the patients, including evaluation of shorter courses of therapy and the development of newer and better tolerated antiparasitic agents.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure

Keywords: Antiparasitic Agents, Chagas Disease, Heart Failure, Nitroimidazoles, Primary Prevention, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Trypanocidal Agents, Triazoles, Trypanosoma cruzi


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