Posaconazole as a trypanocidal drug: global efficacy and their impact in animal models of Chagas disease

BISIO, MARGARITA; JURADO MEDINA, LAURA; GARCÍA-BOURNISSEN, FACUNDO; GULIN, ERNESTO

Mar del Plata

Congreso; Reunión Sociedades de Biociencias; 2023

SAIC-AAFE-AB-AACyTAL

Systematic reviews (SR) and meta-analysis (MA) contribute to the 3Rs in animal research by formally summarizing existing data without requiring new animal experiments. After promising results inin vitro and in vivo models, posaconazole (POS) was evaluated in human patients with indeterminate phase of Chagas disease. However, POS therapeutic trials were unexpected failures. Previously,we conducted an SR (PROSPERO #205000) to summarize animal models and assess the risk of bias. In this work, we analyzed the overall efficacy of POS in Trypanosoma cruzi infection, using survival,cure rate and maximum parasitemia as endpoints. MA was performed by comparing outcomes from POS, infected non-treated (INT) and positive control (i.e., benznidazole (BZ) or nifurtimox(NFX)) animals. Anticipating a high heterogeneity, the analysis was performed as a random effects model. Survival was compared with risk ratios (RR), and cure rates were compared with odds ratios(OR). Subgroup analysis considered the phase of the disease treatment dose and schemes and T. cruzi strain. POS treatment, compared to INT, led to significantly higher survival (RR=6.14[3.76, 10.02], P