Clinical Investigation of In-vivo Susceptibility of P.Falciparum to Artesunate in Western Cambodia

Summary

There are worrying signs that parasitological responses to the artemisinin drugs for uncomplicated falciparum malaria are slower than elsewhere in the world.If responses to artesunate are poor it is essential to have characterised the blood concentration profile as well as the parasitological response to differentiate resistance from abnormal pharmacokinetics. The primary objective of the study is to assess the level of resistance to artemisinin derivatives in Western Cambodia. A detailed evaluation of 2 different artesunate containing regimens in patients with uncomplicated malaria will be performed. Patients will be randomised to receive either a) Artesunate 2mg/kg/day for 7 days or b) Artesunate 4mg/kg/day for 3 days plus mefloquine 15mg/kg on day 3 and 10mg/kg on day 4 The effect on parasite clearance and cure will be assessed in relation to blood concentrations of the antimalarial drugs ('PK-PD').

Timeline

Start

2007-06

Primary completion

2009-12

Completion

2009-12

Publications

• Mechri M, Epaud R, Emond S, Coulomb A, Jaubert F, Tarrant A, Feldmann D, Flamein F, Clement A, de Blic J, Taam RA, Brunelle F, le Pointe HD. Surfactant protein C gene (SFTPC) mutation-associated lung disease: high-resolution computed tomography (HRCT) findings and its relation to histological analysis. Pediatr Pulmonol. 2010 Oct;45(10):1021-9. doi: 10.1002/ppul.21289.
• Anderson TJ, Nair S, Nkhoma S, Williams JT, Imwong M, Yi P, Socheat D, Das D, Chotivanich K, Day NP, White NJ, Dondorp AM. High heritability of malaria parasite clearance rate indicates a genetic basis for artemisinin resistance in western Cambodia. J Infect Dis. 2010 May 1;201(9):1326-30. doi: 10.1086/651562.
• Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, Lwin KM, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NP, Lindegardh N, Socheat D, White NJ. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009 Jul 30;361(5):455-67. doi: 10.1056/NEJMoa0808859.

Drugs

Indications