Comparison of Two Regimens of Artemether-lumefantrine for the Treatment of Malaria in Pregnancy

The aim of the current trial is to compare the standard 3-day regimen of artemether-lumefantrine to a 5-day regimen of artemether-lumefantrine in a group of pregnant women and a control of non-pregnant women with uncomplicated P. falciparum malaria. The pharmacokinetics of lumefantrine is modified in pregnancy and the standard regimen used for treatment of adults might not be sufficient to cure malaria, therefore exposing pregnant women to sub-therapeutic drug levels and increased risk of clinical failure. Previous pharmacokinetic studies have shown that the standard 3-day treatment during pregnancy results in reduced plasma concentrations of artemether, dihydroartemisinin and lumefantrine and a faster elimination of lumefantrine. Low lumefantrine plasma concentrations at day 7 are associated with therapeutic failure. Population-based simulations suggest that increased dose and treatment duration are needed for adequate drug exposure in these patients. We propose to assess the pharmacokinetics of a longer regimen of artemether-lumefantrine, (10 doses of artemether-lumefantrine over five days) compared to the standard regimen, (6 doses of artemether-lumefantrine over three days) in a small group of pregnant African women with uncomplicated P. falciparum malaria. The longer regimen should ensure that curative plasma concentration of lumefantrine is reached, and is unlikely to result in any increased frequency of adverse events.

Inclusion criteria

for non pregnant women:

• Age ≥18 and ≤ 45 years
• P. falciparum parasitemia ≥ 100 parasites/μL and less than 200.000 parasites/μL
• Hematocrit ≥21%
• Negative HIV test
• Negative pregnancy test*
• Written informed consent provided
• Willing to stay for 3 or 5 days at the hospital and to comply with the follow-up schedule

Inclusion criteria

for pregnant women (in addition to the above criteria except*):

• Gestational Age ≥ 14 weeks confirmed by ultrasound
• Singleton viable fetus

Exclusion criteria

for non-pregnant women:

• Severe malaria or signs of severe malaria
• Medical conditions requiring concomitant drug treatment or transfer to a different hospital
• Intake of artemether-lumefantrine within the two previous 2 weeks
• Known allergy to the study drugs
• Previous participation in this study or current participation in other studies

Exclusion criteria

for pregnant women (in addition to the above criteria):

• Signs of labour
• Fetal abnormalities identified by ultrasound