Evaluation of the safety and efficacy of dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria in HIV-infected pregnant women: protocol of a multicentre, two-arm, randomised, placebo-controlled, superiority clinical trial (MAMAH project)

TY - JOUR

T1 - Evaluation of the safety and efficacy of dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria in HIV-infected pregnant women: protocol of a multicentre, two-arm, randomised, placebo-controlled, superiority clinical trial (MAMAH project)

AU - González, Raquel

AU - Nhampossa, Tacilta

AU - Mombo-Ngoma, Ghyslain

AU - Mischlinger, Johannes

AU - Esen, Meral

AU - Tchouatieu, André-Marie

AU - Pons-Duran, Clara

AU - Dimessa, Lia Betty

AU - Lell, Bertrand

AU - Lagler, Heimo

AU - Garcia-Otero, Laura

AU - Zoleko Manego, Rella

AU - El Gaaloul, Myriam

AU - Sanz, Sergi

AU - Piqueras, Mireia

AU - Sevene, Esperanca

AU - Ramharter, Michael

AU - Saute, Francisco

AU - Menendez, Clara

N1 - © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2021/11/23

Y1 - 2021/11/23

N2 - INTRODUCTION: Malaria infection during pregnancy is an important driver of maternal and neonatal health especially among HIV-infected women. Intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine is recommended for malaria prevention in HIV-uninfected women, but it is contraindicated in those HIV-infected on cotrimoxazole prophylaxis (CTXp) due to potential adverse effects. Dihydroartemisinin-piperaquine (DHA-PPQ) has been shown to improve antimalarial protection, constituting a promising IPTp candidate. This trial's objective is to determine if monthly 3-day IPTp courses of DHA-PPQ added to daily CTXp are safe and superior to CTXp alone in decreasing the proportion of peripheral malaria parasitaemia at the end of pregnancy.METHODS AND ANALYSIS: This is a multicentre, two-arm, placebo-controlled, individually randomised trial in HIV-infected pregnant women receiving CTXp and antiretroviral treatment. A total of 664 women will be enrolled at the first antenatal care clinic visit in sites from Gabon and Mozambique. Participants will receive an insecticide-treated net, and they will be administered monthly IPTp with DHA-PPQ or placebo (1:1 ratio) as directly observed therapy from the second trimester of pregnancy. Primary study outcome is the prevalence of maternal parasitaemia at delivery. Secondary outcomes include prevalence of malaria-related maternal and infant outcomes and proportion of adverse perinatal outcomes. Participants will be followed until 6 weeks after the end of pregnancy and their infants until 1 year of age to also evaluate the impact of DHA-PPQ on mother-to-child transmission of HIV. The analysis will be done in the intention to treat and according to protocol cohorts, adjusted by gravidity, country, seasonality and other variables associated with malaria.ETHICS AND DISSEMINATION: The protocol was reviewed and approved by the institutional and national ethics committees of Gabon and Mozambique and the Hospital Clinic of Barcelona. Project results will be presented to all stakeholders and published in open-access journals.TRIAL REGISTRATION NUMBER: NCT03671109.

AB - INTRODUCTION: Malaria infection during pregnancy is an important driver of maternal and neonatal health especially among HIV-infected women. Intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine is recommended for malaria prevention in HIV-uninfected women, but it is contraindicated in those HIV-infected on cotrimoxazole prophylaxis (CTXp) due to potential adverse effects. Dihydroartemisinin-piperaquine (DHA-PPQ) has been shown to improve antimalarial protection, constituting a promising IPTp candidate. This trial's objective is to determine if monthly 3-day IPTp courses of DHA-PPQ added to daily CTXp are safe and superior to CTXp alone in decreasing the proportion of peripheral malaria parasitaemia at the end of pregnancy.METHODS AND ANALYSIS: This is a multicentre, two-arm, placebo-controlled, individually randomised trial in HIV-infected pregnant women receiving CTXp and antiretroviral treatment. A total of 664 women will be enrolled at the first antenatal care clinic visit in sites from Gabon and Mozambique. Participants will receive an insecticide-treated net, and they will be administered monthly IPTp with DHA-PPQ or placebo (1:1 ratio) as directly observed therapy from the second trimester of pregnancy. Primary study outcome is the prevalence of maternal parasitaemia at delivery. Secondary outcomes include prevalence of malaria-related maternal and infant outcomes and proportion of adverse perinatal outcomes. Participants will be followed until 6 weeks after the end of pregnancy and their infants until 1 year of age to also evaluate the impact of DHA-PPQ on mother-to-child transmission of HIV. The analysis will be done in the intention to treat and according to protocol cohorts, adjusted by gravidity, country, seasonality and other variables associated with malaria.ETHICS AND DISSEMINATION: The protocol was reviewed and approved by the institutional and national ethics committees of Gabon and Mozambique and the Hospital Clinic of Barcelona. Project results will be presented to all stakeholders and published in open-access journals.TRIAL REGISTRATION NUMBER: NCT03671109.

KW - Antimalarials/adverse effects

KW - Artemisinins

KW - Drug Combinations

KW - Female

KW - HIV Infections/complications

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Infectious Disease Transmission, Vertical/prevention & control

KW - Malaria/drug therapy

KW - Multicenter Studies as Topic

KW - Pregnancy

KW - Pregnancy Complications, Parasitic/drug therapy

KW - Pregnant Women

KW - Quinolines

KW - Randomized Controlled Trials as Topic

U2 - 10.1136/bmjopen-2021-053197

DO - 10.1136/bmjopen-2021-053197

M3 - SCORING: Journal article

C2 - 34815285

VL - 11

JO - BMJ OPEN

JF - BMJ OPEN

SN - 2044-6055

IS - 11

M1 - e053197

ER -