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

HIV Infections Clinical Trial

— PACOME  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00970879
• Other study ID #: IRD-Sidaction-01
• Status: Completed
• Phase: Phase 3
• First received: September 2, 2009
• Last updated: January 21, 2013
• Start date: December 2009
• Est. completion date: December 2012

Study information

• Verified date: January 2013
• Source: Institut de Recherche pour le Developpement
• Contact: n/a
• Is FDA regulated: No
• Health authority: Benin: Comité National Provisoire d'Ethique pour la Recherche en Santé
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 430
• Est. completion date: December 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• HIV Infections
• Malaria
• Malaria in Pregnancy

Intervention

Drug:
• cotrimoxazole
800 mg sulfamethoxazole and 160 mg trimethoprim daily, from 28 weeks of gestation until delivery
• mefloquine
mefloquine 15 mg/Kg three times, between 16 and 28 weeks, 24 and 32 weeks, then 28 and 36 weeks of pregnancy

Locations

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

Sponsors (6)

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

Country where clinical trial is conducted

Benin, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	proportion of placental malaria (presence of parasites in the placental blood smear at delivery)		delivery	No
Secondary	placental malaria mean parasite density at delivery		delivery	No
Secondary	proportion of low birth weight infants (<2500 g) and mean birth weight		delivery	No
Secondary	proportion of maternal anaemia (<11g/dl) and severe maternal anaemia (<8g/dl) at delivery and during pregnancy		course of pregnancy and delivery	No
Secondary	cord blood malaria infection at delivery (infant parasitemia)		delivery	No
Secondary	pre-term deliveries (< 37 weeks)		delivery	No
Secondary	spontaneous abortions (early:<28 weeks, late: =28 weeks) and still births		course of pregnancy	Yes
Secondary	congenital anomalies		first 6 months of life	Yes
Secondary	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)	Yes
Secondary	Mother-to-child HIV transmission rate in each treatment arm		2 months after breastfeeding cessation	No
Secondary	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	No