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.
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 language | English |
|---|---|
| Pages (from-to) | 34-40 |
| Number of pages | 7 |
| Journal | International Journal of Infectious Diseases |
| Volume | 139 |
| Early online date | 25 Nov 2023 |
| DOIs | |
| Publication status | Published - Feb 2024 |
Keywords
- Adjunctive
- Angiopoietin
- Malaria
- Plasmodium falciparum
- Rosiglitazone
- Severe
- Treatment
