Clinical trial NCT00970879: Prevention of Pregnancy-associated Malaria in HIV-infected Women: Cotrimoxazole Prophylaxis Versus Mefloquine
Official title: Prevention of Pregnancy-associated Malaria in HIV-infected Women : Randomised Controlled Trial Testing Cotrimoxazole Prophylaxis Versus Intermittent Preventive Treatment With Mefloquine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malaria in Pregnancy
HIV Infections
Keywords: malaria
pregnancy
HIV
prevention
cotrimoxazole
mefloquine
Lead sponsor: Institut de Recherche pour le Developpement
Sponsor class: OTHER_GOV
Collaborators: name: Sidaction
name: Saint Antoine University Hospital
name: National University Hospital, Cotonou
name: Université d'Abomey-Calavi
name: Ministry of Health, Benin
First posted: 2009-09-03
Enrollment: 430
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the efficacy of cotrimoxazole prophylaxis in prevention of malaria during pregnancy in HIV-infected women, compared to intermittent preventive treatment with mefloquine.

Detailed description: Malaria infection during pregnancy can have adverse effects on both mother and fetus, including maternal anaemia and low birth weight which are responsible for mother and infant mortality. It is a particular problem for women in their first and second pregnancies and for women who are HIV-positive. Maternal HIV infection potentiates many of these adverse effects. In HIV-infected women, the World Health Organization (WHO) advocates the use of insecticide-treated bednets, and drugs : If the CD4 cell count is below 350/mm3 or the HIV disease is in WHO stage 2, 3 or 4, cotrimoxazole prophylaxis for the prevention of pneumocystosis and toxoplasmosis is indicated, that is assumed to also protect those women from malaria. Otherwise, they have to receive at least three doses of intermittent preventive treatment (IPT), most commonly with sulfadoxine-pyrimethamine (SP) given at the antenatal care visits. If IPT with SP has been a subject of many investigations, cotrimoxazole efficacy has never been assessed in prevention of malaria during pregnancy.

The investigators aim to evaluate the efficacy of cotrimoxazole prophylaxis in prevention of malaria during pregnancy in HIV-infected women. The investigators postulate that cotrimoxazole prophylaxis is not inferior to IPT in all women, unrelated to their CD4 cell count. In the control arm, the investigators will use mefloquine as IPT. The safety and efficacy of this drug have already been assessed in HIV-negative patients (NCT00274235).

A randomized controlled trial will be conducted in five hospitals in Benin. Pregnant women will be enrolled both in the Antenatal Care unit and in the Infectious Diseases unit of each setting. All women will receive insecticide-treated bednets at enrolment. Randomization will be stratified by hospital and CD4 cell count range. Women assigned to cotrimoxazole will receive cotrimoxazole prophylaxis daily during all the course of pregnancy. Women assigned to mefloquine IPT will receive mefloquine three times during pregnancy. Women randomised in this arm and having a low CD4 cell count or an advanced HIV disease will also receive cotrimoxazole prophylaxis in prevention of HIV/AIDS opportunistic infections. Drug efficacy will be judged on the prevalence of placental malaria at delivery.

This study will contribute to updating the recommendations concerning the prevention of malaria during pregnancy in HIV-infected women.

Eligibility criteria: Inclusion Criteria:

* Confirmed HIV seropositivity
* Permanent residency in the study catchment's area
* Confirmed pregnancy, gestational age\< 28 weeks
* More than 18 years of age
* Karnofsky index ≥80
* Willingness to deliver at the hospital
* Written informed consent

Exclusion Criteria:

* History of allergy to study drugs : sulpha drugs, mefloquine, quinine
* History or presence of major illnesses : severe renal disease , severe hepatic disease, severe neuropsychiatric disease
* Mefloquine or halofantrine received within the 4 weeks prior to enrolment

Primary outcomes:
measure: proportion of placental malaria (presence of parasites in the placental blood smear at delivery)
timeFrame: delivery
Secondary outcomes:
measure: placental malaria mean parasite density at delivery
timeFrame: delivery
measure: proportion of low birth weight infants (<2500 g) and mean birth weight
timeFrame: delivery
measure: proportion of maternal anaemia (<11g/dl) and severe maternal anaemia (<8g/dl) at delivery and during pregnancy
timeFrame: course of pregnancy and delivery
measure: cord blood malaria infection at delivery (infant parasitemia)
timeFrame: delivery
measure: pre-term deliveries (< 37 weeks)
timeFrame: delivery
measure: spontaneous abortions (early:<28 weeks, late: ≥28 weeks) and still births
timeFrame: course of pregnancy
measure: congenital anomalies
timeFrame: first 6 months of life
measure: safety profile of the two treatments: proportion and detailed description of adverse effects in each treatment arm
timeFrame: course of pregnancy (mother) anf first 6 months of life (infant)
measure: Mother-to-child HIV transmission rate in each treatment arm
timeFrame: 2 months after breastfeeding cessation
measure: To document the effect of cotrimoxazole in reducing infections in HIV-infected women, we will measure the incidence of bacterial and parasitic infections (other than malaria) during pregnancy
timeFrame: course of pregnancy
Other outcomes:
Locations:
city: Cotonou
country: Benin
facility: Hôpital d'Instruction des Armées Camp Guézo
city: Cotonou
country: Benin
facility: Hôpital de la Mère et de l'Enfant Lagune
city: Cotonou
country: Benin
facility: Hôpital de zone de Suru Lere
city: Cotonou
country: Benin
facility: Unviversity Hospital Hubert Koutoukou Maga
city: Porto-Novo
country: Benin
facility: Clinique Louis Pasteur
Study officials:
affiliation: Cotonou University Hospital & Faculté des Sciences de la Santé, Benin
name: Marcel D Zannou, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Saint Antoine Hospital, Assistance Publique-Hôpitaux se Paris
name: Pierre-Marie Girard, Professor
role: STUDY_CHAIR
affiliation: Institut de Recherche pour le Developpement
name: Michel Cot, MD, PHD
role: STUDY_DIRECTOR
References:
citation: Duvignaud A, Denoeud-Ndam L, Akakpo J, Agossou KV, Afangnihoun A, Komongui DG, Atadokpede F, Dossou-Gbete L, Girard PM, Zannou DM, Cot M. Incidence of malaria-related fever and morbidity due to Plasmodium falciparum among HIV1-infected pregnant women: a prospective cohort study in South Benin. Malar J. 2014 Jul 4;13:255. doi: 10.1186/1475-2875-13-255.