Artemisone for the Treatment of Uncomplicated Falciparum Malaria in Western Cambodia
Status:
Withdrawn
Trial end date:
2010-10-01
Target enrollment:
Participant gender:
Summary
It has now been demonstrated clearly that in Western Cambodia parasitological responses to
artesunate and artemether containing treatment regimens for uncomplicated falciparum malaria
are slower than elsewhere in the world. Median parasite clearance time (PCT) in patients
treated with artesunate 4 mg/kg/day was 78 hours and with 2 mg/kg/day 82 hours, compared to
54 and 48 hours, respectively, in Western Thailand; at 72hours peripheral blood parasitaemia
was still detectable in 55% of patients in Western Cambodia, compared to 7.5% in Western
Thailand. Although occasional poor responses to artesunate have been described previously the
current reports suggest a consistent problem. These antimalarials are central to current
treatment strategies, and so spread of parasites with reduced artemisinin susceptibility
outside this area would be a disaster. A recent consensus meeting Pnomh Penh agreed that this
should indeed be termed resistance, and represented a major threat to malaria control.
Radical containment measures would be needed. This study aims to address whether a
semi-synthetic or fully synthetic peroxide antimalarial would be more effective than
artesunate and could therefore be used in Cambodia as part of the elimination strategy.
Artemisone is a semisynthetic derivative of dihydroartemisinin, which importantly changes its
tertiary structure. This drug has also shown promising efficacy for the treatment of
uncomplicated falciparum malaria in phase II trials in Thailand and seems to be at least as
efficacious as artesunate. No significant toxicity has been reported for artemisone and it is
very well tolerated. If sensitivity for artemisone has remained intact in Western Cambodia,
this will have important implications for the strategies available for containment of the
threatening problem of artesunate resistance in Western Cambodia. It will also have important
implications for further development of these drugs for the use in artemisinin combination
therapies (ACTs).