New drug for Chagas disease shows antitrypanosomal activity [CHAGASAZOL trial]

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1. Posaconazole showed anti-trypanosomal activity, but there was a high rate of treatment failure 10 months after treatment. 

2. Posaconazole had fewer serious adverse events than benznidazole. 

Evidence Rating Level: 1 (Excellent) 

Study Rundown: Chagas disease is caused by the parasite Trypanosoma cruzi which in its chronic form leads to cardiac and gastrointestinal pathology. Treatment options for chronic Chagas disease are limited. Benznidazole is considered standard of care but has shown mixed results for treatment of chronic disease and is associated with considerable side effects.

This study tested a new agent, posaconazole, against benznidazole for treatment of chronic Chagas disease. The study found that while posaconazole has anti-trypanosomal activity and fewer adverse effects, it did not produce as durable of a response as benznidazole. Treatment response in this study was evaluated with a quantitative PCR assay for parasite DNA in the blood.

Defining treatment endpoints in Chagas disease has been challenging. The clinically relevant end point is cardiac or gastrointestinal dysfunction. However, these may take years to manifest and progress. Serological conversion may also take years after treatment to occur. This study used a quantitative PCR method to find evidence of parasites in the blood. This had the benefit of enabling ongoing assessment of response to treatment, accepting the assumption that parasite DNA in the blood reflects parasite burden in the body. It should be noted that this PCR method has been shown to be highly specific but not sensitive. As such, the study’s results likely underestimate treatment failure. These results indicate that posaconazole may be useful for suppression of T. cruzi infection. Further studies to assess whether long-term suppressive therapy with posaconazole may slow or stop progression of chronic Chagas disease are warranted.

Click to read the study, published today in NEJM

Click to read the accompanying editorial in NEJM

Relevant Reading: Development of a real-time PCR assay for Trypanosoma cruzi detection in blood samples

In-Depth [randomized controlled trial]: Seventy-nine patients were randomized in a 1:1:1 ratio to high-dose posaconazole, low-dose posaconazole and benznidazole groups for 60 days of treatment. The patients were then followed for 10 months after treatment. Treatment failure 10 months after treatment was observed in 80-90% of patients who took posaconazole per-protocol compared to 6% of patients who took benznidazole per-protocol. In the intention-to-treat analysis, treatment failure was about the same in the posaconazole group (80-90%) while it was higher (38%) in the benznidazole group, reflecting the fact that 5 patients had to discontinue benznidazole owing to side effects while no posaconazole patients discontinued treatment.

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