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

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Varo, R ORCID: 0000-0003-4282-5572, Crowley, VM ORCID: 0000-0002-2593-1130, Mucasse, H, Sitoe, A, Bramugy, J ORCID: 0000-0002-2350-5584, Serghides, L ORCID: 0000-0002-2817-6134, Weckman, AM ORCID: 0000-0002-2200-4008, Erice, C ORCID: 0000-0001-9681-6861, Bila, R, Vitorino, P et al (show 10 more authors) , Mucasse, C, Valente, M, Ajanovic, S, Balanza, N ORCID: 0000-0002-3581-0383, Zhong, K, Derpsch, Y, Gladstone, M ORCID: 0000-0002-2579-9301, Mayor, A ORCID: 0000-0003-3890-2897, Bassat, Q ORCID: 0000-0003-0875-7596 and Kain, KC (2024) Adjunctive rosiglitazone treatment for severe pediatric malaria: A randomized placebo-controlled trial in Mozambican children International Journal of Infectious Diseases, 139. pp. 34-40. ISSN 1201-9712, 1878-3511

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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.

Item Type:	Article
Uncontrolled Keywords:	Adjunctive, Treatment, Plasmodium falciparum, Malaria, Severe, Rosiglitazone, Angiopoietin
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	19 Feb 2024 08:39
Last Modified:	28 Feb 2026 15:00
DOI:	10.1016/j.ijid.2023.11.031
Open Access URL:	https://doi.org/10.1016/j.ijid.2023.11.031
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3178759
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