Safe and Efficacious Artemisinin-based Combination Treatments for African Pregnant Women with Malaria: A Multicentre Randomized Control Trial

Autor: Maaike De Crop, Linda Kalilani Phiri, Victor Mwapasa, Yves Claeys, Jean-Pierre Van Geertruyden, Umberto D'Alessandro, Modest Mulenga, Innocent Valea, Maminata Traore, Harry Tagbor, Joris Menten, Gertrude Kalanda, David Mwakazanga, Céline Schurmans, Tinto Halidou, Kamala Thriemer, Michael Nambozi, Raffaella Ravinetto, Theonest K. Mutabingwa
Přispěvatelé: Pregact Grp
Rok vydání: 2015
Předmět:
Pediatrics
Malawi
Artemether/lumefantrine
Malaria in pregnancy
Artesunate
Ghana
law.invention
Fetal Development
Study Protocol
Randomized controlled trial
law
Pregnancy
Obstetrics and Gynaecology
Clinical endpoint
Birth Weight
Artemether
Diagnosis & treatment
education.field_of_study
Obstetrics and Gynecology
Artemisinin-based therapy
Artemisinins
Mefloquine
Drug Combinations
Ethanolamines
Prenatal Exposure Delayed Effects
Quinolines
Female
medicine.drug
Adult
medicine.medical_specialty
Sub-Saharan
Population
Zambia
Antimalarials
Burkina Faso
parasitic diseases
medicine
Humans
education
Fluorenes
business.industry
Pregnant women
Artemether
Lumefantrine Drug Combination
Infant
Newborn
Amodiaquine
medicine.disease
Placentation
Surgery
Malaria
Clinical trial
Reproductive Medicine
Pregnancy Complications
Parasitic
Human medicine
business
Follow-Up Studies
Zdroj: Reproductive Health
Reproductive health
ISSN: 1742-4755
Popis: Background Asymptomatic and symptomatic malaria during pregnancy has consequences for both mother and her offspring. Unfortunately, there is insufficient information on the safety and efficacy of most antimalarials in pregnancy. Indeed, clinical trials assessing antimalarial treatments systematically exclude pregnancy for fear of teratogenicity and embryotoxicity. The little available information originates from South East Asia while in sub-Saharan Africa such information is still limited and needs to be provided. Design A Phase 3, non-inferiority, multicentre, randomized, open-label clinical trial on safety and efficacy of 4 ACT when administered during pregnancy was carried out in 4 African countries: Burkina Faso, Ghana, Malawi and Zambia. This is a four arm trial using a balanced incomplete block design. Pregnant women diagnosed with malaria are randomised to receive either amodiaquine-artesunate (AQ-AS), dihydroartemisinin-piperaquine (DHA-PQ), artemether-lumefantrine (AL), or mefloquine-artesunate (MQAS). They are actively followed up until day 63 post-treatment and then monthly until 4–6 weeks post-delivery. The offspring is visited at the time of the first birthday. The primary endpoint is treatment failure (PCR adjusted) at day 63 and safety profiles. Secondary endpoints included PCR unadjusted treatment failure up to day 63, gametocyte carriage, Hb changes, placenta malaria, mean birth weight and low birth weight. The primary statistical analysis will use the combined data from all 4 centres, with adjustment for any centre effects, using an additive model for the response rates. This will allow the assessment of all 6 possible pair-wise treatment comparisons using all available data. Discussion The strength of this trial is the involvement of several African countries, increasing the generalisability of the results. In addition, it assesses most ACTs currently available, determining their relative ‘-value-’ compared to others. The balanced incomplete block design was chosen because using all 4-arms in each site would have increased complexity in terms of implementation. Excluding HIV-positive pregnant women on antiretroviral drugs may be seen as a limitation because of the possible interactions between antiretroviral and antimalarial treatments. Nevertheless, the results of this trial will provide the evidence base for the formulation of malaria treatment policy for pregnant women in sub-Saharan Africa. Trial registration NCT00852423
Databáze: OpenAIRE
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