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

This study has been completed.
Sponsor:
Collaborators:
Sidaction
Saint Antoine University Hospital
National University Hospital, Cotonou
Université d'Abomey-Calavi
Ministry of Health, Benin
Information provided by (Responsible Party):
Lise Denoeud-Ndam, Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier:
NCT00970879
First received: September 2, 2009
Last updated: January 21, 2013
Last verified: January 2013

September 2, 2009
January 21, 2013
December 2009
July 2012   (final data collection date for primary outcome measure)
proportion of placental malaria (presence of parasites in the placental blood smear at delivery) [ Time Frame: delivery ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00970879 on ClinicalTrials.gov Archive Site
  • placental malaria mean parasite density at delivery [ Time Frame: delivery ] [ Designated as safety issue: No ]
  • proportion of low birth weight infants (<2500 g) and mean birth weight [ Time Frame: delivery ] [ Designated as safety issue: No ]
  • proportion of maternal anaemia (<11g/dl) and severe maternal anaemia (<8g/dl) at delivery and during pregnancy [ Time Frame: course of pregnancy and delivery ] [ Designated as safety issue: No ]
  • cord blood malaria infection at delivery (infant parasitemia) [ Time Frame: delivery ] [ Designated as safety issue: No ]
  • pre-term deliveries (< 37 weeks) [ Time Frame: delivery ] [ Designated as safety issue: No ]
  • spontaneous abortions (early:<28 weeks, late: ≥28 weeks) and still births [ Time Frame: course of pregnancy ] [ Designated as safety issue: Yes ]
  • congenital anomalies [ Time Frame: first 6 months of life ] [ Designated as safety issue: Yes ]
  • safety profile of the two treatments: proportion and detailed description of adverse effects in each treatment arm [ Time Frame: course of pregnancy (mother) anf first 6 months of life (infant) ] [ Designated as safety issue: Yes ]
  • Mother-to-child HIV transmission rate in each treatment arm [ Time Frame: 2 months after breastfeeding cessation ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: course of pregnancy ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Prevention of Pregnancy-associated Malaria in HIV-infected Women: Cotrimoxazole Prophylaxis Versus Mefloquine
Prevention of Pregnancy-associated Malaria in HIV-infected Women : Randomised Controlled Trial Testing Cotrimoxazole Prophylaxis Versus Intermittent Preventive Treatment With Mefloquine

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
  • Malaria in Pregnancy
  • HIV Infections
  • 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
  • Experimental: cotrimoxazole (high)
    CD4 cell count≥350/mm3
    Intervention: Drug: cotrimoxazole
  • Active Comparator: mefloquine
    CD4 cell count≥350/mm3
    Intervention: Drug: mefloquine
  • Experimental: cotrimoxazole (low)
    CD4 cell count<350/mm3
    Intervention: Drug: cotrimoxazole
  • Active Comparator: mefloquine & cotrimoxazole
    CD4 cell count<350/mm3
    Interventions:
    • Drug: cotrimoxazole
    • Drug: mefloquine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
430
December 2012
July 2012   (final data collection date for primary outcome measure)

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
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Benin
 
NCT00970879
IRD-Sidaction-01
Yes
Lise Denoeud-Ndam, Institut de Recherche pour le Developpement
Institut de Recherche pour le Developpement
  • Sidaction
  • Saint Antoine University Hospital
  • National University Hospital, Cotonou
  • Université d'Abomey-Calavi
  • Ministry of Health, Benin
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
Institut de Recherche pour le Developpement
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP