PACOME: Prevention of Pregnancy-associated Malaria in HIV-infected Women: Cotrimoxazole Prophylaxis Versus Mefloquine

Sponsor

Institut de Recherche pour le Developpement (Other)

Overall Status

Completed

CT.gov ID

NCT00970879

Collaborator

Sidaction (Other), Saint Antoine University Hospital (Other), National University Hospital, Cotonou (Other), Université d'Abomey-Calavi (Other), Ministry of Health, Benin (Other)

430

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

2.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Malaria in Pregnancy HIV Infections	Drug: cotrimoxazole Drug: mefloquine	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

430 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Prevention of Pregnancy-associated Malaria in HIV-infected Women : Randomised Controlled Trial Testing Cotrimoxazole Prophylaxis Versus Intermittent Preventive Treatment With Mefloquine

Study Start Date :

Dec 1, 2009

Actual Primary Completion Date :

Jul 1, 2012

Actual Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: cotrimoxazole (high) CD4 cell count≥350/mm3	Drug: cotrimoxazole 800 mg sulfamethoxazole and 160 mg trimethoprim daily, from 28 weeks of gestation until delivery
Active Comparator: mefloquine CD4 cell count≥350/mm3	Drug: mefloquine mefloquine 15 mg/Kg three times, between 16 and 28 weeks, 24 and 32 weeks, then 28 and 36 weeks of pregnancy
Experimental: cotrimoxazole (low) CD4 cell count<350/mm3	Drug: cotrimoxazole 800 mg sulfamethoxazole and 160 mg trimethoprim daily, from 28 weeks of gestation until delivery
Active Comparator: mefloquine & cotrimoxazole CD4 cell count<350/mm3	Drug: cotrimoxazole 800 mg sulfamethoxazole and 160 mg trimethoprim daily, from 28 weeks of gestation until delivery Drug: mefloquine mefloquine 15 mg/Kg three times, between 16 and 28 weeks, 24 and 32 weeks, then 28 and 36 weeks of pregnancy

Outcome Measures

Primary Outcome Measures

proportion of placental malaria (presence of parasites in the placental blood smear at delivery) [delivery]

Secondary Outcome Measures

placental malaria mean parasite density at delivery [delivery]
proportion of low birth weight infants (<2500 g) and mean birth weight [delivery]
proportion of maternal anaemia (<11g/dl) and severe maternal anaemia (<8g/dl) at delivery and during pregnancy [course of pregnancy and delivery]
cord blood malaria infection at delivery (infant parasitemia) [delivery]
pre-term deliveries (< 37 weeks) [delivery]
spontaneous abortions (early:<28 weeks, late: ≥28 weeks) and still births [course of pregnancy]
congenital anomalies [first 6 months of life]
safety profile of the two treatments: proportion and detailed description of adverse effects in each treatment arm [course of pregnancy (mother) anf first 6 months of life (infant)]
Mother-to-child HIV transmission rate in each treatment arm [2 months after breastfeeding cessation]
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 [course of pregnancy]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country
1	Hôpital d'Instruction des Armées Camp Guézo	Cotonou	Benin
2	Hôpital de la Mère et de l'Enfant Lagune	Cotonou	Benin
3	Hôpital de zone de Suru Lere	Cotonou	Benin
4	Unviversity Hospital Hubert Koutoukou Maga	Cotonou	Benin
5	Clinique Louis Pasteur	Porto-Novo	Benin

Sponsors and Collaborators

Institut de Recherche pour le Developpement
Sidaction
Saint Antoine University Hospital
National University Hospital, Cotonou
Université d'Abomey-Calavi
Ministry of Health, Benin

Investigators

Principal Investigator: Marcel D Zannou, Professor, Cotonou University Hospital & Faculté des Sciences de la Santé, Benin
Study Chair: Pierre-Marie Girard, Professor, Saint Antoine Hospital, Assistance Publique-Hôpitaux se Paris
Study Director: Michel Cot, MD, PHD, Institut de Recherche pour le Developpement