Safe and Efficacious Artemisinin-based Combination Treatments for African Pregnant Women With Malaria

Summary

Malaria is the most important human parasitic disease and is responsible of high morbidity and mortality in resource-poor countries. Pregnant women, who are a high-risk group, are almost always excluded from clinical trials; thus, the investigators lack sufficient information on the safety and efficacy of most antimalarials in pregnancy. The recommendation of the World Health Organization to use artemisinin combination therapy (ACT) in the 2nd and 3rd trimester is already implemented in several African countries, however documentation of their efficacy and safety in pregnancy is still limited. Thus, the investigators propose to evaluate the efficacy and safety of 4 ACT(artemether-lumefantrine, amodiaquine-artesunate, mefloquine-artesunate and dihydroartemisinin-piperaquine), when used to treat pregnant women with P. falciparum malaria; the results will help to recommend the optimal therapy for this high-risk group in Africa.

Conditions

• Malaria in Pregnancy

Interventions

DRUG

Dihydroartemisinin-piperaquine

DHA-PQ tablets are green film coated intended for oral use and contain 20/160mg or 40/320mg of dihydroartemisinin (DHA) and piperaquine phosphate (PQ) respectively. In this trial the 40/320mg for adults will be used. Developed by Sigma Tau in partnership with Medicines for Malaria Venture.

DRUG

Artesunate-mefloquine

MQAS will be provided as a fixed-dose ACT. There are 2 strengths (AS25+MQ55mg and AS100+MQ220mg) and dosing regimen is calculated according to 12 mg/kg AS and 24mg/kgMQ total dose over three days. Pregnant women will receive 2 tablets/day for 3 days. It is developed by Farmanguinhos with the Drugs for Neglected Diseases Initiative. To be noted: if the FDCs will not get the WHO pre-qualification before the start of recruitment, the separate AS and MQ will be used

DRUG

Artesunate-amodiaquine

AQAS, developed by teh DNDi with Sanofi-Aventis and manufactured by Sanofi-Aventis, has been pre-qualified by the WHO in 2008 and is available in several African countries, including those involved in this trial. AQ-AS tablets are round, yellow on one side and white-slightly yellow on the other, with a breaking bar, AS engraved on one side and either 25, 50 or 100 on the other side. Tablets to be used in this trial are those 100mg/270mg AS/AQ, containing 100 mg of artesunate, 352.640 mg of amodiaquine hydrochloride corresponding to 270mg of amodiaquine base.

DRUG

Artemether-lumefantrine

AL (tablets containing a FDC of 20 mg of artemether and 120 mg of lumefantrine) is manufactured by Novartis and has been extensively used in Africa for the treatment of uncomplicated malaria. AL was registered in Switzerland in 1999, has since received marketing authorisation in several endemic and non-endemic countries and it is WHO pre-qualified.

Sponsors & Collaborators

• National Institute for Medical Research, Tanzania

  collaborator OTHER_GOV

• Kwame Nkrumah University of Science and Technology

  collaborator OTHER

• Centre Muraz

  collaborator OTHER

• Kamuzu University of Health Sciences

  collaborator OTHER

• Tropical Diseases Research Centre, Zambia

  collaborator OTHER_GOV

• Institute of Tropical Medicine(KIT), Amsterdam

  collaborator UNKNOWN

• Liverpool School of Tropical Medicine

  collaborator OTHER

• Institute of Tropical Medicine, Belgium

  lead OTHER

Principal Investigators

• Umberto D'Alessandro, MD · Institute Tropical Medicine Belgium and MRC Unit in The Gambia

• Tinto Halidou, PharmD · Centre Muraz

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

15 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-06-30

Primary Completion

2013-10-31

Completion

2015-04-30

Countries

• Burkina Faso
• Ghana
• Malawi
• Zambia

Study Locations