Adjunctive rosiglitazone treatment for severe pediatric malaria: A randomized placebo-controlled trial in Mozambican children
Rosauro Varo, Valerie M Crowley, Humberto Mucasse, Antonio Sitoe, Justina Bramugy, Lena Serghides, Andrea M Weckman, Clara Erice, Rubao Bila, Pio Vitorino, Campos Mucasse, Marta Valente, Sara Ajanovic, Núria Balanza, Kathleen Zhong, Yiovanna Derpsch, Melissa Gladstone, Alfredo Mayor, Quique Bassat, Kevin C Kain, Rosauro Varo, Valerie M Crowley, Humberto Mucasse, Antonio Sitoe, Justina Bramugy, Lena Serghides, Andrea M Weckman, Clara Erice, Rubao Bila, Pio Vitorino, Campos Mucasse, Marta Valente, Sara Ajanovic, Núria Balanza, Kathleen Zhong, Yiovanna Derpsch, Melissa Gladstone, Alfredo Mayor, Quique Bassat, Kevin C Kain
Abstract
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.
Keywords: Adjunctive; Angiopoietin; Malaria; Plasmodium falciparum; Rosiglitazone; Severe; Treatment.
Conflict of interest statement
Declaration of competing interest The authors do not hold a patent for this indication of rosiglitazone. Rosauro Varo had a fellowship from the program Río Hortega of the Instituto de Salud Carlos III (ISCIII) (CD16/00024) while the study was conducted.
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
Source: PubMed