Adjunctive rosiglitazone treatment for severe paediatric malaria: A randomized placebo-controlled trial in Mozambican children

Varo, Rosauro, Crowley, Valerie M., Mucasse, Humberto, Sitoe, Antonio, Bramugy, Justina, Serghides, Lena, Weckman, Andrea M., Erice, Clara, Bila, Rubao, Vitorino, Pio, Mucasse, Campos, Valente, Marta, Ajanovic, Sara, Balanza, Núria, Zhong, Kathleen, Derpsch, Yiovanna ORCID:, Gladstone, Melissa, Mayor, Alfredo, Bassat, Quique and Kain, Kevin C. (2024) Adjunctive rosiglitazone treatment for severe paediatric malaria: A randomized placebo-controlled trial in Mozambican children. International Journal of Infectious Diseases, 139. pp. 34-40. ISSN 1201-9712

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Objective: 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 versus 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 four 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: One hundred eighty children were enrolled; 91 were assigned to rosiglitazone and 89 to placebo. Children that received rosiglitazone had a steeper rate of decline of Angpt-2 over the first 96h of hospitalization compared to children that received placebo; however, the trend was not significant (P = 0.288). A similar non-significant trend was observed for Angpt-1 (P = 0.65) and the Angpt-2/Angpt-1 ratio (P = 0.347). All other secondary and safety outcomes were similar between groups (P > 0.05).   Conclusions: Adjunctive rosiglitazone at this dosage was safe and well tolerated but did not significantly affect the longitudinal kinetics of circulating Angpt-2.

Item Type: Article
Additional Information: Funding information: This study was funded in part by the Canadian Institutes of Health Research (CIHR) Foundation Grant FDN-148439 (KCK), a Canada Research Chair in Molecular Parasitology (KCK; and LS) and the Thomas Mather Fund (LS and KCK). Funders had no role in the design, conduct or decision to publish this study. CISM is supported by the Government of Mozambique and the Spanish Agency for International Development (AECID). ISGlobal receives support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. This research is part of ISGlobal's Program on the Molecular Mechanisms of Malaria, which is partially supported by the Fundación Ramón Areces. The manufacturer of rosiglitazone (AvandiaⓇ, GlaxoSmithKline) had no role in this study. NB is supported by an FPU predoctoral fellowship from the Spanish Ministry of Universities (FPU18/04260).
Uncontrolled Keywords: adjunctive,angiopoietin,malaria,plasmodium falciparum,rosiglitazone,severe,treatment,microbiology (medical),infectious diseases,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2726
Faculty \ School: Faculty of Social Sciences > School of Psychology
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Depositing User: LivePure Connector
Date Deposited: 02 Dec 2023 03:34
Last Modified: 09 Jan 2024 01:37
DOI: 10.1016/j.ijid.2023.11.031


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