Randomised Trial of 3 Artemisinin Combination Therapy for Malaria in Pregnancy

• Status: Active, not recruiting
• Trial end date: 2021-01-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a randomised, open label trial, comparing standard dose of dihydroartemisinin-piperaquine (DP) with standard fixed artesunate-mefloquine regimen (MAS3) and with a longer regimen of artemether-lumefantrine (ALN+) in the treatment of uncomplicated malaria in pregnant women. The sample size is 335 women in each arm which would be 1005 women in total. Pregnant patients in 2nd and 3rd trimester with acute uncomplicated malaria who meet eligibility criteria will be asked to participate in the study. The primary objective is to determine if the efficacy of DP and MAS3 are superior to ALN+ in the treatment of uncomplicated malaria in pregnancy. The study will also incorporate a dense pharmacokinetic study of mefloquine and artesunate (15 women in the MAS3 arm) and a population pharmacokinetic study for mefloquine, piperaquine and lumefantrine.

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

Details

• Lead Sponsor: University of Oxford
• Treatments: Artemether; Artemether-lumefantrine combination; Artemisinine; Artemisinins; Artenimol; Artesunate; Dihydroartemisinin; Lumefantrine; Mefloquine; Piperaquine

Criteria

Inclusion Criteria:

• Age 18-45 years

• Viable pregnancy of any gestation as assessed by ultrasound scanning

• Microscopically confirmed uncomplicated malaria (parasitaemia ≥ 5/500 WBC) with Plasmodium falciparum or Mixed infection (i.e. P.falciparum & P.vivax/ovale/malariae) or Plasmodium vivax/ovale/malariae

• Willingness and ability to comply with the study protocol for the duration of the trial

• Written informed consent provided

• No signs of labour

Additional criteria for patients in the detailed pharmacokinetic study group (N=24 in the MAS3 arm):

• HCT>25% (based on field reading i.e. capillary sample)

• P.falciparum monoinfection

• Agree to stay in the clinic for 7 days

• Written consent to participate the detailed PK subgroup

Exclusion Criteria:

• Known hypersensitivity to the study drugs

• P.falciparum asexual stage parasitaemia ≥ 4% RBCs

• Clinical or laboratory features of severe malaria based on WHO criteria-Appendix 1

• Gastrointestinal dysfunction that could alter absorption or motility

• History or known liver diseases or other chronic diseases (excluding thalassemia & G6PD deficiency)

• Presence of intercurrent illness or any condition which in the judgement of the investigator would place the patient at undue risk or interfere with the results of the study

• Splenectomy

• Hematocrit (HCT) <20% (based on field reading i.e. capillary sample) [ *NB: Dense mefloquine pharmacokinetic exclusion if HCT < 25%]

• Taking contraindicated medications

• History of narcotic or alcohol abuse