Quantifying anti-trypanosomal treatment effects in chronic indeterminate Chagas disease: an individual patient data meta-analysis of two proof of concept trials
Abstract
Abstract Background The current antiparasitic treatment for chronic Chagas disease of 8 weeks daily benznidazole or nifurtimox is poorly tolerated and reaches only a small minority of those with chronic infections. Defining parasitological cure is compromised by the low blood trypomastigote densities, which fluctuate close to or below the limit of qPCR detection. Methods To address this limitation and improve the assessment of parasitological cure we developed a probabilistic model of therapeutic efficacy based on serial qPCR data. We pooled clinical and laboratory data from two prospective trials in Bolivian adults with chronic indeterminate Chagas disease. In both trials randomised arms included placebo or standard of care benznida-zole (300mg/day for 8 weeks). In the first trial, the experimental arms were fosravuconazole monotherapies (400mg/week for 4 or 8 weeks, or 200mg/week for 8 weeks); in the second trial the experimental arms were shorter or lower dose benznidazole regimens (300mg/day for 2 or 4, or 150mg/day for 4 weeks), or combinations of fosravuconazole 300mg weekly for 8 weeks with either benznidazole 150mg/day for 4 weeks or benznidazole 300mg/week for 8 weeks. Serial parasite densities were estimated from triplicate qPCRs targeting T. cruzi satellite DNA taken from one to three 5 or 10ml blood samples at 8-12 visits over one year. Treatment efficacies were estimated under a hierarchical Bayesian model, taking as input serial cycle threshold (Ct) data…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 441 participants or records.
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