Bio-availability of Rectal Artesunate in Children With Severe Falciparum Malaria

The study aims at describing the pharmacokinetic properties of rectal artesunate in well characterized severely ill patients using intravenous artesunate as a comparator.

Individually randomized, open label, 2-arm, cross-over, clinical trial. Patients are allocated to receive rectal artesunate at admission and intravenous artesunate after 12 hours or intravenous artesunate at admission and rectal artesunate after 12 hours. All patients are treated for severe malaria with intravenous quinine. Frequent blood samples are taken at fixed intervals after the administration of the first and the second dose of study drug. The time frame is 24 hours and thereafter patients continue the standard antimalarial therapy.

Inclusion Criteria:

• Weight ≥6 kilograms and ≤ 34 kilograms
• Severe malaria (WHO Guidelines 2013; Appendix 1)
• P. falciparum infection confirmed by Rapid Diagnostic Test (P. falciparum monoinfection or mixed infection with P. ovale or P. malariae)
• Parents or guardian signed Informed Consent

Exclusion Criteria:

• Acute diarrhoea defined as > 3 liquid stools in the previous 24 hours
• Visible anorectal malformations or a disease of the rectum
• Known hypersensitivity to quinine or artesunate
• A documented history of an effective dose of parenteral antimalarial in the preceding 24 hours or a single dose of rectal artesunate in the previous 12 hours or a dose of an artemisinin based combination therapy in the previous 6 hours
• Co-morbidity which in the judgement of the investigator would interfere with the patient treatment or results of the study or place the subject at undue risk
• Participation in another clinical trial or earlier in the same clinical trial