Recruitment completed for clinical trial evaluating parenteral artesunate regimen for children with severe malaria

The Severe Malaria in African Children network (SMAC) completed enrolment of patients for the phase III artesunate follow-up study led by Prof. Kremsner (University of Tübingen). A total of 1,046 children with severe malaria are enrolled in this study and the end of follow-up period for the last patient enrolled is expected to be reached by the end of October 2012. The primary objective of the study is to further evaluate simplification of the treatment of severe malaria by administering artesunate in a three-dose regimen intramuscularly rather than intravenously.

The overall goal of this Phase III Comparative, Open-Label, Dose and Regimen Optimisation Follow-up Study is to compare the efficacy, safety and tolerability of three-dose regimens: intravenous (iv) artesunate and intramuscular (im) artesunate simplified dosing regimens (4 mg/kg artesunate at 0, 24 and 48 hours; 12 mg/kg total dose) and the standard iv 5-dose regimen (2.4 mg/kg artesunate at 0, 12, 24, 48 and 72 hours; 12 mg/kg total dose).

If the outcome of this study is positive, further simplification of the treatment of severe malaria by administering artesunate in a  three-dose regimen intramuscularly will contribute to reducing costs and improving severe malaria management in resource limited settings. These results will inform future policy and evidence-based changes in the WHO guidelines for malaria treatment.

Collaboration
The sponsor of the clinical trial is the University of Tübingen (Germany). The clinical trial sites are in Gabon (Albert Schweitzer Hospital in Lambaréné and the Université de Médecine et Science de la Santé in Libreville), Ghana (School of Medical Sciences, Kumasi), Kenya (KEMRI Coast in Kilifi and KEMRI Kondele Children’s Hospital in Kisumu), Malawi (Queen Elizabeth Central Hospital, Blantyre), and The Gambia (MRC laboratories, Banjul). Supporting sites are in Austria (University of Innsbruck, Innsburck and the Vienna School of Clinical Research, Vienna), Germany (Institut für klinische Pharmacologie, Stuttgart), United Kingdom (St George’s Hospital Medical School, London). The study is cofunded by the Federal Ministry of Education and Research (Germany).

Earlier SMAC phase II study
The earlier SMAC phase II multicentre clinical trial, also coordinated by Prof. Peter G. Kremsner, proved that a shorter anti-malaria treatment is equally effective as the longer standard regimen in treating children with severe malaria. It was shown that three doses over two days of the drug artesunate delivered intravenously are as effective as five doses over three days. The results for the SMAC studies on artesunate treatment for severe malaria were published online in the Journal of Infectious Diseases in December 2011 (doi: 10.1093/infdis/jir724).

More information

• Registration at PACTR, the Pan African Clinical Trials Registry: PACTR201102000277177