A phase I/II randomized controlled clinical trial to assess the feasibility, safety, and preliminary effectiveness of paracetamol in resolving acute kidney injury in children with severe malaria.

BACKGROUND

Acute kidney injury (AKI) is prevalent among children with severe malaria, contributing to considerable morbidity and mortality. Oxidative stress has been implicated in the pathophysiology of malaria-induced AKI, and paracetamol, with its antioxidant properties, has been proposed as a solution. This phase I/II randomized trial evaluated paracetamol as a potential renoprotective adjunct in children with severe malaria and acute kidney injury.

METHODS

We conducted a phase I/II open label parallel randomized controlled trial of 40 hospitalized children aged > 6 months to < 12 years with malaria-induced AKI in eastern Uganda. Participants were randomized by a sealed envelope 1:1 to receive either oral paracetamol 20 mg/kg 6 hourly for 48 h or tepid sponging every 30 min until fever subsided. Only the assessors of the primary outcome were masked to the intervention. The primary outcome was renal recovery at 48 h assessed using restricted mean survival time (RMST) in intention to treat population of children according to their randomization groups.

RESULTS

Between 19 September 2021 and 25 August 2023, 250 children with hemoglobinuric severe malaria were screened and the 40 enrolled were randomly assigned paracetamol (n = 20) or tepid sponging (n = 20). The mean age was 6.54 (2.61) years. The mean time to renal recovery in the paracetamol group was 0.491 h (95% CI, -9.265 to 10.248; p = 0.921) longer than the control group within 48 h, but this difference was not statistically significant even after adjusting for age and weight: 1.04 h (95% CI, -8.61 to 10.70; p = 0.832). The safety assessment indicated no significant differences in adverse events and hepatotoxicity in either group.

CONCLUSIONS

Although paracetamol was safe, it did not significantly improve renal recovery in children with malaria-induced AKI. Further larger studies are needed to explore this role of paracetamol.

TRIAL REGISTRATION: ISRCTN84974248. Registered on August 12, 2020.