Adjunctive rosiglitazone treatment for severe pediatric malaria: A randomize d placebo-controlle d trial in Mozambican children

Objectives: We tested the hypothesis that adjunctive rosiglitazone treatment would reduce levels of circulating angiopoietin-2 (Angpt-2) and improve outcomes of Mozambican children with severe malaria.Methods: A randomized, double-blind, placebo-controlled trial of rosiglitazone vs placebo as adjunctive treatment to artesunate in children with severe malaria was conducted. A 0.045 mg/kg/dose of rosiglitazone or matching placebo were administered, in addition to standard of malaria care, twice a day for 4 days. The primary endpoint was the rate of decline of Angpt-2 over 96 hours. Secondary outcomes included the longitudinal dynamics of angiopoietin-1 (Angpt-1) and the Angpt-2/Angpt-1 ratio over 96 hours, parasite clearance kinetics, clinical outcomes, and safety metrics.Results: Overall, 180 children were enrolled; 91 were assigned to rosiglitazone and 89 to placebo. Children who received rosiglitazone had a steeper rate of decline of Angpt-2 over the first 96 hours of hospitalization compared to children who received placebo; however, the trend was not significant ( P = 0.28). A similar non-significant trend was observed for Angpt-1 ( P = 0.65) and the Angpt-2/Angpt-1 ratio ( P = 0.34). All other secondary and safety outcomes were similar between groups ( P > 0.05).Conclusion: Adjunctive rosiglitazone at this dosage was safe and well tolerated but did not significantly affect the longitudinal kinetics of circulating Angpt-2.(c) 2023 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )