The purpose of this study is to compare four regimens using US FDA GMP intravenous artesunate for the treatment of uncomplicated Plasmodium falciparum malaria to identify the most effective treatment regimen as determined by rapidity of parasite clearance by microscopy.
To compare the efficacy and tolerability of intravenous artesunate for the initial treatment of uncomplicated Plasmodium falciparum malaria at doses that bracket anticipated clinical doses (2.4 mg/kg once daily for 3 days; or 2.4 mg/kg initially, at 12 hours on Day 0, and then daily on Day 1 and 2) and thereby establish the safest, highly efficacious dosing regimen for use in future clinical trials.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
120
New Nyanza Provincial Hospital
Kisumu, Nyanza, Kenya
Kwai River Christian Hospital
Sangkhla Buri, Kanchanaburi, Thailand
The primary endpoint for this pharmacodynamic study is clearance of falciparum parasites from the blood.
Reference microscopic interpretation of Giemsa-stained thick and thin blood smears for malaria will serve as the diagnostic method of parasitemia detection.
Parasite clearance will be quantified using a discrete variable denoting efficacy to clear at least 90% of asexual parasites from the peripheral blood by 48 hours after administration of IV artesunate
Additional measures of parasite clearance will also be assessed.
A continuous variable of time to parasite reduction milestones:
parasite clearance time (PCT90 and PCT100), and parasite reduction ratios (PRR12h and PRR24h) at defined time points , and
A continuous variable of area under the curve (AUC) of quantifiable parasitemia
Tolerability of the treatment regimens will also be assessed throughout the study through use of evaluation for adverse events and safety laboratories to include hematology and chemistry tests.
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