|
Project Topic
|
Malaria in pregnancy is a major cause of maternal anaemia and low birth weight, resulting in significant maternal and infant mortality/morbidity, poor growth and infant development. Though artemisinin-based combination therapies (ACT) are currently recommended for the treatment of malaria in the 2nd and 3rd trimesters of pregnancy, their tolerability, safety and efficacy vary considerably, limiting treatment options. There is the need to find alternative treatment options for pregnant women with good efficacy, safety, and tolerability. Pyronaridine-artesunate (PA), the latest ACT registered, is well tolerated in children and non-pregnant adults for single and repeated treatment and has similar efficacy to artemether-lumefantrine (AL) or mefloquine-artesunate (MAS). Although PA has shown good safety and tolerability profile in pre-clinical studies, there is insufficient information to recommend its use during pregnancy. The main objective of this proposal is to determine PA’s efficacy, safety (primary endpoints) in African pregnant women (2nd or 3rd trimester) with uncomplicated falciparum malaria, and thus provide the necessary information to include this treatmentin the guidelines for the management of malaria during pregnancy, thus contributing to reduce the unacceptable burden of malaria among pregnant women. We propose to implement a three-arm multicentre randomized open label trial in 5 African countries (Burkina Faso, Mali, The Gambia, Democratic Republic of the Congo and Mozambique). Women in the 2nd or 3rd trimester of pregnancy and with malaria will be randomized to one of three treatments: PA, dihydroartemisin-piperaquine (DP) or AL, and followed up untilday 63 post-treatment, and at 4-6 weeks after delivery. The main hypothesis is that PA efficacy is non-inferior to DP or AL. Primary endpoint measures include one for efficacy and another for safety. Efficacy endpoint is PCR-adjusted cure rate atday 63. Secondary endpoints will include parasite and fever clearance time, haematological recovery, gametocyte carriage,PCR unadjusted cure rate at day 63, placental malaria, and outcome of pregnancy. Safety endpoints will be (severe) adverseevents, laboratory abnormalities, cardiac and hepatic toxicity. Exploratory endpoints will include PA’s pharmacokinetics, and its interaction with antiretrovirals in a subsample of HIVpositive women. For capacity building, the project will include a series of short term training (on clinical trial methodology and ICH standards,research ethics, molecular biology, placental histopathology, statistics, scientific writing and research management) and longterm training (5 MSc, 2 PhD). Targeted dissemination activities will facilitate maximizing the impact of the study findings.
|
