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

• Published in: International journal of infectious diseases 2024-02, Vol.139, p.34-40
• Main Authors: 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, Gladstone, Melissa, Mayor, Alfredo, Bassat, Quique, Kain, Kevin C
• Format: Article
• Language: English
• Subjects: Adjunctive; Antimalarials - adverse effects; Artesunate - therapeutic use; Child; Double-Blind Method; Humans; Malaria; Malaria - drug therapy; Malaria, Falciparum - drug therapy; Mozambique; Plasmodium falciparum; Rosiglitazone; Rosiglitazone - therapeutic use; Severe; Treatment
• ISSN: 1201-9712; 1878-3511
• DOI: 10.1016/j.ijid.2023.11.031

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. 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. 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). Adjunctive rosiglitazone at this dosage was safe and well tolerated but did not significantly affect the longitudinal kinetics of circulating Angpt-2.