Adjunctive rosiglitazone treatment for severe paediatric 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

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)34-40
Number of pages7
JournalInternational Journal of Infectious Diseases
Volume139
Early online date25 Nov 2023
DOIs
Publication statusPublished - Feb 2024

Keywords

  • Adjunctive
  • Angiopoietin
  • Malaria
  • Plasmodium falciparum
  • Rosiglitazone
  • Severe
  • Treatment

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