title: Safe and efficacious artemisinin-based combination treatments for African pregnant women with malaria: a multicentre randomized control trial.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Michael
authors.initials: M
authors.lastname: Nambozi
authors.forename: Modest
authors.initials: M
authors.lastname: Mulenga
authors.forename: Tinto
authors.initials: T
authors.lastname: Halidou
authors.forename: Harry
authors.initials: H
authors.lastname: Tagbor
authors.forename: Victor
authors.initials: V
authors.lastname: Mwapasa
authors.forename: Linda Kalilani
authors.initials: LK
authors.lastname: Phiri
authors.forename: Gertrude
authors.initials: G
authors.lastname: Kalanda
authors.forename: Innocent
authors.initials: I
authors.lastname: Valea
authors.forename: Maminata
authors.initials: M
authors.lastname: Traore
authors.forename: David
authors.initials: D
authors.lastname: Mwakazanga
authors.forename: Yves
authors.initials: Y
authors.lastname: Claeys
authors.forename: Céline
authors.initials: C
authors.lastname: Schurmans
authors.forename: Maaike
authors.initials: M
authors.lastname: De Crop
authors.forename: Joris
authors.initials: J
authors.lastname: Menten
authors.forename: Raffaella
authors.initials: R
authors.lastname: Ravinetto
authors.forename: Kamala
authors.initials: K
authors.lastname: Thriemer
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Van Geertruyden
authors.forename: Theonest
authors.initials: T
authors.lastname: Mutabingwa
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium. udalessandro@mrc.gm.
authors.forename: Umberto
authors.initials: U
authors.lastname: D'Alessandro
mesh_terms: D000328:Adult; D000655:Amodiaquine / Q000009:adverse effects / Q000627:therapeutic use; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use*; D000077332:Artesunate; D001724:Birth Weight / Q000187:drug effects; D002050:Burkina Faso; D004338:Drug Combinations; D004983:Ethanolamines / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005449:Fluorenes / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D005869:Ghana; D006801:Humans; D007231:Infant, Newborn; D008288:Malaria / Q000188:drug therapy*; D008295:Malawi; D015767:Mefloquine / Q000009:adverse effects / Q000627:therapeutic use; D010929:Placentation / Q000187:drug effects; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000188:drug therapy*; D011297:Prenatal Exposure Delayed Effects; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use; D015024:Zambia; D010879:Piperazines
chemical_list: D000655:Amodiaquine; D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D000077332:Artesunate; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D015767:Mefloquine; D011804:Quinolines; C515299:amodiaquine, artesunate drug combination; C039060:artenimol; C034759:piperaquine; D010879:Piperazines