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PREGACT: Safety and efficacy of four artemisinin-based combination treatments in African pregnant women with malaria

10 March 2016

The results of the clinical trial PREGACT were published in the New England Journal of Medicine on 10 March 2016. The study was conducted to compare four antimalarial drug combinations for treating pregnant women. The authors concluded that based on safety and efficacy, DHA-PQ (dihydroartemisinin with piperaquine) seems the most suitable treatment for uncomplicated malaria in pregnancy. The results are expected to inform WHO treatment guidelines.

“We congratulate Professor D’Alessandro and the study team with these important results. This study underlines the value of collaborative research and its impact. This is one of the very few large and well-designed studies on a special population group with paucity of data. We believe that these results will inform policy and positively contribute towards improved health care practice in this high-risk population group involving mothers and their babies”

Dr Michael Makanga, EDCTP Executive Director

Malaria in pregnancy is a major public health problem in endemic countries. In view of its harmful effects during pregnancy, it is extremely important to adequately treat malaria. However, few studies on antimalarial drugs have been carried out in pregnant women. As a high-risk group pregnant women are usually excluded from clinical trials for fear of teratogenicity. This has hindered the development of evidence-based recommendations for the prevention and treatment of malaria during pregnancy.

In the second and third trimester of pregnancy, WHO guidelines recommend a 3-day course with artemisinin-based combination therapy (ACT) known to be effective in the country/region, or clindamycin with either 7 days of artesunate or quinine. Though experience with the use of ACTs in pregnancy is increasing, it is still limited, particularly in sub-Saharan Africa. It is expected that the results of the study will feed directly into the WHO malaria treatment guidelines, in particular, regarding the performance of dihydroartemisinin-piperaquine for which no recommendation could be made in the current malaria treatment guidelines due to lack of data.

“The PREGACT trial provides the evidence base for the recommendations of ACT for pregnant women infected with malaria.”

Prof. Umberto D’Alessandro, PREGACT Project Coordinator

PREGACT

The PREGACT trial – Safe and efficacious artemisinin-based combination treatments for African pregnant women with malaria – was led by Professor Umberto D’Alessandro (previously Institute of Tropical Medicine, Belgium; currently MRC The Gambia Unit). For the trial 3,428 pregnant women with confirmed malaria infection were recruited in four countries (Burkina Faso, Ghana, Malawi and Zambia) in order to test the safety and efficacy of artemisinin-based combination therapies (dihydroartemisinin-piperaquine, mefloquine-artesunate, amodiaquine-artesunate and artemether-lumefantrine) when administered to pregnant women with P. falciparum infection during the second and the third trimester. The trial was completed in 2014.

Funding
It was funded by the European Developing Countries Clinical Trials Partnership (EDCTP) and by the Malaria in Pregnancy Consortium, which is funded through a grant from the Bill and Melinda Gates Foundation to the Liverpool School of Tropical Medicine. In addition, it benefited from the support of the following institutions: Belgian Development Cooperation Agency, Liverpool School of Tropical Medicine, Medical Research Council UK, Netherlands Organisation for Scientific Research (NWO). The total project budget was approximately € 6.5 million to which EDCTP contributed almost €3 million. The study drugs were provided by the Drugs for Neglected Diseases Initiative (Geneva), Novartis (Basel), Sanofi Aventis (Paris, France), and Sigma-Tau Industrie Farmaceutiche Riunite S.p.A (Roma, Italy).

More information

Publication
Umberto D’Alessandro et al.: The Safety and Efficacy of Four Artemisinin-Based Combination Treatments in African Pregnant Women with Malaria, New England Journal of Medicine 2016; 374:913-927 10 March 2016

Full list of authors and affiliations
D’Alessandro, Umberto – London School of Hygiene and Tropical Medicine,
Disease Control / Medical Research Council The Gambia Unit, United Kingdom / The Gambia
Tinto, Halidou – Centre Muraz, Parasitology, Burkina Faso
Traore-Coulibaly, Maminata – Centre Muraz, Parasitology, Burkina Faso
Tahita, Marc – Institut de Recherche en Sciences de la Santé, Centre Muraz, Burkina Faso
Valea, Innocent – Institut de Recherche en Sciences de la Santé, Centre
Muraz, Burkina Faso
Nambozi, Michael – Tropical Diseases Research Center, Clinical Sciences, Zambia
Mulenga, Modest – Tropical Diseases Research Centre, Zambia
Hachizovu, Sebastian – Tropical Diseases Research Center, Clinical Sciences, Zambia
Kabuya, Jean – Tropical Diseases Research Centre, Zambia
Mulenga, Joyce – Tropical Diseases Research Center, Clinical Sciences, Zambia
Ravinetto, Raffaella – Institute of Tropical Medicine, Clinical Trials Unit
Menten, Joris – Institute of Tropical Medicine, Clinical Trials Unit, Belgium
Thriemer, Kamala – Institute of Tropical Medicine, Clinical Trials Unit, Belgium
De Crop, Maaike – Institute of Tropical Medicine, Belgium
Claeys, Yves – Institute of Tropical Medicine, Belgium
Schurmans, Celine – Institute of Tropical Medicine, Belgium
Van Overmeir, Chantal – Institute of Tropical Medicine, Belgium
Geertruyden, Jean Pierre – Antwerp University, Faculty of Medicine and
Health Sciences, Belgium
Tagbor, Harry – School of Public Health, Kwame Nkrumah University of Science and Technology, Ghana
Antwi, Gifty – School of Public Health, Kwame Nkrumah University of Science and Technology, Ghana
Pekyi, Divine – Centre for Global Health Research, Canada
Ampromfi, Akua – Centre for Global Health Research, Canada
Gbekor, Prosper – Juaben Government Hospital, Ghana
Mwapasa, Victor – University of Malawi, College of Medicine, Malawi
Kalilani-Phiri, Linda – University of Malawi, College of Medicine, Malawi
Kalanda, Gertrude – University of Malawi, College of Medicine, Malawi
Madanitsa, Mwayiwawo – University of Malawi, College of Medicine, Malawi
Mutabingwa, Theonest – Hubert Kairuki Memorial University, Tanzania

 

MRC The Gambia Unit