Evaluating prescriber preferences for the treatment of indeterminate Chagas disease (EPPIC study): an international survey

Background: Benznidazole (BNZ) and nifurtimox (NFX) remain the only approved treatments for Trypanosoma cruzi infection, but both are associated with frequent adverse drug reactions (ADRs), long treatment duration, and limited accessibility, resulting in poor treatment adherence and premature discontinuation. Recent clinical trials have evaluated shorter and lower-dose regimens; however, the minimum level of efficacy considered acceptable by healthcare providers – in the context of improved safety and greater accessibility – has not been systematically investigated. This study aimed to identify prescriber-defined efficacy thresholds and the factors influencing prescribing preferences for new antiparasitic regimens for Chagas disease. Methods: We conducted an international, cross-sectional, web-based survey between June and August 2024 among healthcare providers, researchers, and public health practitioners with experience in Chagas disease from endemic and non-endemic countries. The survey assessed satisfaction with current antiparasitic drugs, perceived treatment disadvantages, and the willingness of practitioners to prescribe hypothetical new regimens with varying efficacy levels and additional clinical attributes. Results: Thirty of 50 invited participants completed the survey (60% response rate); most were physicians or nurses (57%), and 76% had more than six years of experience managing Chagas disease. An efficacy threshold of 70% or above was associated with substantially higher prescribing willingness: 46.7% of respondents reported being likely or very likely to prescribe a regimen with 70-79% efficacy, compared with 20.0% for 60-69% and 6.7% for 50-59%. Willingness to prescribe regimens with moderate efficacy (60-69%) was increased when regimens offered prevention of mother-to-child transmission, reduced ADR frequency and severity, or the possibility of second-line use. Improved accessibility was an additional determinant for regimen in the lowest efficacy range. Respondents identified ADRs, long treatment duration, and limited drug availability as the main disadvantages of current therapies. Conclusions: This study provides preliminary, provider-level evidence that prescriber acceptance of new antiparasitic regimens for T. cruzi infection is shaped by the overall benefit-risk profile, not efficacy alone. A 70% efficacy threshold emerged as a critical inflection point for prescribing willingness, while prevention of mother-to-child transmission, improved tolerability, and greater accessibility were identified as key factors that could support the adoption of regimens with moderate efficacy. These findings may inform the design of future clinical trials and the development of treatment strategies aligned with real-world prescribing priorities.