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

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: Female

Summary

Malaria in pregnancy is a major cause of maternal and newborn morbidity and mortality in sub-Saharan Africa]. Effective antimalarial preventive and treatment regimens can significantly reduce malaria-related morbidity and mortality in the mother and baby. However, therapeutic choices are limited by concerns about possible toxicity to the fetus and because of these concerns pregnant women are normally excluded from clinical trials. This, combined with the lack of adverse events reporting system, results in a scarcity of data on drug safety and efficacy in pregnancy. Moreover, changes in the maternal physiology in pregnancy often alter the pharmacokinetic of drugs. Artemether-lumefantrine (ALN) is a highly efficacious artemisinin-based combination therapy approved by the World Health Organisation for use in the 2nd and 3rd trimesters, although it is still infrequently used in pregnancy and there is uncertainty as to the optimum dose. The pharmacokinetics of ALN are altered in pregnancy, resulting in reduced plasma concentrations and while the standard adult dose is still effective in high transmission settings, where pregnant women have higher levels of immunity, efficacy is reduced significantly in low transmission settings where women have lower levels of immunity. Inadequate antimalarial treatment dosing in pregnancy risks treatment failure or breakthrough infection and exposure of malaria parasites to sub-therapeutic drug concentrations thus selecting for drug resistance.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Oxford
• Collaborator: University of Kinshasa
• Treatments: Artemether; Artemether-lumefantrine combination; Artemether, Lumefantrine Drug Combination; Artemisinins; Lumefantrine

Criteria

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