A phase I trial in Kenyan and Zambian children hospitalised with severe malaria tested adjunctive sevuparin as three infusions at 0, 8 and 16 hours. Twenty-three children were enrolled and 20 were included in the primary analysis. Model-guided escalation and dose-limiting APTT prolongation led to a maximum tolerated dose of 3 mg/kg per infusion. This is an early safety and dose-finding result, not evidence of clinical efficacy.
Key findings
- Twenty-three children were enrolled and 20 entered the primary analysis across 10 cohorts; the final dose was 3 mg/kg per infusion.
- Two dose-limiting toxicities occurred at 6 mg/kg, with further DLTs during de-escalation at 5 and 4 mg/kg.
- There was one death among 23 participants (4.3%), one readmission and one grade 3 non-DLT event; investigators judged all unrelated to sevuparin.
Why this matters globally
Severe childhood malaria still has high mortality and lacks proven adjunctive therapies. The study supplies a dose and safety basis for later trials, but should not change treatment practice before larger controlled efficacy studies.
Thai researcher contribution
Nicholas P. J. Day and Arjen M. Dondorp of the Mahidol Oxford Tropical Medicine Research Unit contributed severe-malaria and trial expertise to the African hospital network.
Limitations to consider
The sample comprised only 23 children, with 20 in the primary analysis, no control arm and no power to assess mortality or efficacy. Findings from Kenyan and Zambian children may not generalise to other settings.