A clinical trial evaluates drug combinations for the treatment of asymptomatic Chagas patients

ISGlobal participated in an international clinical trial (STOP-CHAGAS) that evaluated the efficacy of two drugs, alone or combined, in eliminating Trypanosoma cruzi in infected adult patients. Using the detection of parasite DNA as therapeutic efficacy readout, the study shows that the combination of two drugs (benznidazole and posaconazole) does not provide added benefit as compared to benznidazole monotherapy, and highlights the need to develop new antiparasitic drugs that are effective and safe.

An estimated 6 million people worldwide are currently infected with Trypanosoma cruzi, the parasite causing Chagas disease. Although many do not present symptoms, 30 to 40 per cent of them will end up developing heart and digestive complications. A recent publication estimates that 200,000 people will die from Chagas cardiomyopathy in the next 5 years. The available treatments against T. cruzi are less effective in adults than in the younger population, and therefore it is urgent to find new drugs or new combinations of existing drugs to treat these patients.

The goal of the STOP-CHAGAS trial was to evaluate, for the first time, the efficacy of a combination of two drugs to eliminate the parasite in asymptomatic adult patients. The multicentric randomized clinical trial was performed with 120 patients from 19 centres in 5 Latinoamerican countries and Spain. The patients were divided in 4 groups that received treatment (placebo, benznidazole, posaconazole, or both) during 60 days. The presence – or not- of parasite was determined by DNA amplification methods at 6 and 12 months. The results indicate that posaconazole was very effective in the first 60 days but its effect was not sustained, in contrast to benznidazole whose effect was maintained up to one year after treatment initiation in 87% of the cases (100% of those who finished the treatment). However, 30% of benznidazole-treated patients interrupted the treatment due to side effects. The combination of both drugs had no added benefits compared with benznidazole monotherapy.

“These results underline the need to find new drugs or alternative regimes that help decrease the secondary effects of benznidazole and improve treatment efficacy” says Joaquim Gascon, director of the Chagas Initiative and study co-author, “as well as the need to develop new and better tolerated drugs for the treatment of chronically infected adult patients”.