Quantifying anti-trypanosomal treatment effects in chronic indeterminate Chagas disease: a secondary analysis of individual patient data from two proof-of-concept trials
Abstract
BACKGROUND
Determining parasitological cure in chronic Chagas disease is compromised by very low blood trypomastigote densities, which fluctuate close to or below the limit of quantitative PCR (qPCR) detection (approximately one parasite per 10 mL). We aimed to improve the statistical methodology used to analyse serial qPCR data to estimate treatment efficacy.
METHODS
In this secondary analysis, we pooled clinical and laboratory data from two prospective randomised controlled trials (E1224 [NCT01489228] and BENDITA [NCT03378661]) in Bolivian adults (aged 18-50 years) with chronic indeterminate Chagas disease. Both trials included positive and negative control groups, consisting of placebo and standard of care benznidazole (300 mg per day for 8 weeks), respectively. In E1224, participants were enrolled between July 19, 2011, and July 26, 2012, and the experimental groups were fosravuconazole monotherapies (400 mg per week for 4 weeks or 8 weeks, or 200 mg per week for 8 weeks); in BENDITA, participants were enrolled between Nov 30, 2016, and July 27, 2017, and the experimental groups were shorter or lower-dose benznidazole regimens (300 mg per day for 2 weeks or 4 weeks, or 150 mg per day for 4 weeks), or combinations of fosravuconazole 300 mg weekly for 8 weeks with either benznidazole 150 mg per day for 4 weeks or benznidazole 300 mg per week for 8 weeks. Triplicate qPCRs were done on one to three blood samples taken at eight to 12 follow-up visits over 1 year. The primary…
How strong is the evidence?
Evidence Hub reads this as a secondary / pooled analysis, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 441 participants or records.
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