A 30-day benznidazole regimen offers safer Chagas disease treatment option

A 30-day course of benznidazole taken once a day could offer people with chronic Trypanosoma cruzi infection a safer and more practical option than the current standard treatment, taken twice a day for 60 days. The TESEO trial - co-led by The University of Texas at El Paso, the CEADES Foundation in Bolivia and the Barcelona Institute for Global Health (ISGlobal) - results are reported today in The Lancet Infectious Diseases.

TESEO is the first randomized clinical trial to evaluate benznidazole and nifurtimox head-to-head under identical conditions, with sustained follow-up to detect parasites in the blood by PCR for three years."  

Igor Almeida, Ph.D., professor of biological sciences at UTEP and co-senior author of the study

Corresponding authors and co-senior authors of the study were Faustino Torrico (CEADES) and Joaquim Gascón (ISGlobal).

Trypanosoma cruzi infection affects more than seven million people worldwide, mainly in Latin America, and is a growing public health concern in the United States, Europe and Japan. About 30-40% of infected people develop Chagas disease, with serious heart or digestive complications, yet fewer than 1% are diagnosed and treated. The only two drugs, benznidazole and nifurtimox, are given in regimens set more than 50 years ago, which frequently cause side effects like headaches, nausea, joint pain and fever, resulting in up to 31% of patients stopping treatment early.

Six treatment strategies compared over three years

The phase 2b clinical trial enrolled 450 adults at three centers in Bolivia and randomly assigned them to six groups. Three received benznidazole: two pills daily for 60 days (the standard regimen); one pill daily for 30 days; or one daily for 90 days. The other three received nifurtimox: two pills daily for 60 days (the standard regimen); two daily for 30 days; or one daily for 90 days. The researchers recorded drug-related adverse events and tested participants' blood for parasite DNA over three years.

Fewer side effects with 30 days of benznidazole 

Only the 30-day benznidazole regimen significantly reduced side effects: 37% of participants had a drug-related adverse event, compared with 60% on the standard regimen, meaning nearly 40% fewer patients were affected. It was also easier to follow, with 83% of patients completing treatment without interruption, compared with 60%. Most side effects appeared within the first two weeks, regardless of treatment length, and almost all resolved.

Halved treatment was just as effective

Three years after treatment, the parasite remained undetectable in the blood of 94% of participants in the 30-day group, compared with 95% in the standard group, demonstrating the treatment's non-inferiority. The 30-day regimen, the team said, therefore offered the best balance between benefits and harms of the six strategies tested. The nifurtimox regimens were less effective overall.

"The improved safety profile of the shorter benznidazole regimen, combined with once-daily dosing, has the potential to substantially increase the proportion of patients who complete treatment," says Gascón. 

The 30-day course also uses a quarter of the drug: "We can treat four patients with the same amount of drug we previously used for one," adds Torrico.

What TESEO means for UTEP

The seven-year trial, funded by an approximately $8 million award from the National Institute of Allergy and Infectious Diseases, was completed despite the COVID-19 pandemic, with partial support from UTEP's Border Biomedical Research Center (BBRC).

"TESEO is a landmark for the College of Science and for UTEP. It is the first clinical trial our University has sponsored, and it has produced a result that could change how Chagas disease is treated around the world," said Marc Knecht, Ph.D., dean of the College of Science.

"The BBRC is a hub for biomedical research at UTEP that strengthens our focus on health disparities that affect the communities we serve," said Michael Kenney, Ph.D., director of the BBRC. "TESEO shows what that investment can deliver."

"TESEO shows that a research program built in our department can lead an international clinical trial with results that matter to patients worldwide," said Kendal Hirschi, Ph.D., chair of the Department of Biological Sciences and co-director of the BBRC.

Next steps

Larger phase 3 trials are needed to confirm these results before the 30-day regimen can be incorporated into treatment guidelines, and people currently receiving treatment for Chagas disease should continue the regimen prescribed by their doctor, the team said.