Pharmacokinetic of Mefloquine-Artesunate in Plasmodium Falciparum Malaria Infection in Pregnancy

• Status: Completed
• Trial end date: 2009-07-01
• Target enrollment: 0
• Participant gender: Female

Summary

Malaria in pregnancy is a major public health problem in Sub-Saharan Africa. Over the past decades, P. falciparum has shown increasing resistance to chloroquine and Sulphadoxine-Pyrimethamine, which has prompted a change in treatment approach; artemisinin containing combination therapies (ACTs) are now the standard treatment of P. falciparum malaria in areas with established resistance to traditional therapies. However, a standard approach for using ACT in pregnancy does not exist in Africa, where some countries keep on using quinine, while others allow the use of ACTs. Thus, there is need of establishing the safety and efficacy of ACTs in malaria-infected pregnant women. Since the pharmacokinetic of antimalarials may be altered during pregnancy and since available pharmacokinetic data are still somewhat limited, we propose to carry out a study confirming or disproving existing pharmacokinetic data (collected in South-East Asia), before starting any larger African efficacy and safety trials. The fixed-dose combination mefloquine-artesunate (MQ-AS), developed by the Drugs for Neglected Diseases Initiative, will be used in the study, which will compare the pharmacokinetics of MQ-AS for treatment of P.falciparum in 24 pregnant women in the second and third trimesters, to the pharmacokinetics of this regimen in 24 matched non-pregnant P.falciparum infected women. The study will be carried out in Burkina Faso.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institute of Tropical Medicine, Belgium
• Collaborators: Centre Muraz; Liverpool School of Tropical Medicine
• Treatments: Artemisinins; Artesunate; Mefloquine

Criteria

Inclusion Criteria:

1. Plasmodium falciparum monoinfection (any density)

2. At least 18 years old;

3. Haemoglobin at leats 7 g/dL;

4. Residence within the health facility catchment's area;

5. Willing to adhere to the study requirements

6. Willing to deliver in health facility

7. Ability to provide written informed consent

8. EITHER pregnant women in the 2nd or 3rd trimester (cases)or non-pregnant women between the ages of 18 and 49 years (controls).

Exclusion Criteria:

1. Pregnancy 1st trimester

2. History of known pregnancy complications or bad obstetric history such as repeated stillbirths or eclampsia;

3. Known major illnesses likely to influence pregnancy outcome including diabetes mellitus, severe renal or heart disease, or active tuberculosis;

4. Current cotrimoxazole prophylaxis or ARV treatment;

5. Any significant presenting illness that requires hospitalization, including severe malaria;

6. Intent to move out of the study catchment area before delivery or deliver at relative's home out of the catchment area.

7. Prior enrollment in the study or concurrent enrollment in another study.

8. Unable to take oral medication

9. Clear evidence of treatment with antimicrobials with antimalarial activity (erythromycin or other macrolides, co-trimoxazole or other sulfonamides, any tetracycline including doxycycline, quinolones and clindamycin) or exposure to antimalarial drugs within the week prior enrollment.

10. History of allergy or hypersensivity to interventional drugs

11. Patients taking drugs with possible interaction with study drugs (i.e. digoxin or warfarin)

12. History or family history of epilepsy or psychiatric disorder

13. Presence of signs and symptoms of severe malaria

14. Inability to tolerate oral medication (repeated vomiting, impairment of consciousness). Vomiting of any of the treatment doses will lead to exclusion from the pharmacokinetic sampling.