Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Sunday, August 7, 2022

A phase-2, randomized, multicenter, placebo-controlled, proof-of-concept trial of oral fexinidazole in adults with chronic indeterminate Chagas disease

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Chagas disease (CD) has significant global health impact, but safe and effective treatments remain elusive. The nitroimidazole fexinidazole is a potential treatment.
Methods
This double-blind, randomised, placebo-controlled, dose-finding, proof-of-concept study was conducted in Bolivia. Adults with serologically-confirmed chronic indeterminate CD and positive PCR were randomly assigned to one of six fexinidazole regimens (1200 or 1800 mg/day for 2, 4, or 8 weeks) or placebo. Target recruitment was 20 patients/arm. The primary endpoint was sustained parasitological clearance by serial negative qPCR from end of treatment (EOT) until 6 months follow-up in the intention-to-treat population (ITT). Follow-up was extended to 12 months.
Results
Enrollment was interrupted after 4/47 patients presented with transient asymptomatic grade-3 and 4 neutropenia. Treatment of ongoing patients was stopped in all patients ad ministered >2 weeks. A total of 40 patients received from 3 days to 8 weeks of treatment with fexinidazole. Delayed onset neutropenia (n = 8) and increased liver enzymes (n = 8) were found in fexinidazole patients, versus none in the placebo arm. In the ITT analysis, sustained parasitological clearance from EOT to 12 months follow-up varied between 66.7% ("1200mg-2week") and 100.0% ("1800mg-2week"). Rapid, sustained clearance of parasitemia was observed in all treated patients with available data, but not in any patients in the placebo group, at 12 months (p = 0.0056). Further exploratory exposure-response analysis suggested low dosages of fexinidazole may be safe and effective.
Conclusions
Further evaluation is needed to establish fexinidazole's minimum effective dosage and risk-benefit relationship. Results suggest potential for effective treatment regimens of <10 days.
View on Web

No comments:

Post a Comment