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CompletedNCT00970879PACOMEUpdated Jan 23, 2013

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

A Phase 3 interventional study of cotrimoxazole and mefloquine in Malaria in Pregnancy and HIV Infections, sponsored by Institut de Recherche pour le Developpement. Completed at 5 sites in Benin. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2013-01-23.

Sponsored by Institut de Recherche pour le Developpement · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
430
Allocation
Randomized
Ages
18 Years and older
Sex
Female
01

Study 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.

Read the 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.

02

Conditions studied

  • Malaria in Pregnancy
  • HIV Infections

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Keywords

  • malaria
  • pregnancy
  • HIV
  • prevention
  • cotrimoxazole
  • mefloquine
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
430 participants (actual)

Study arms

  • Experimental
    cotrimoxazole (high)

    CD4 cell count≥350/mm3

    Drug: cotrimoxazole

  • Active comparator
    mefloquine

    CD4 cell count≥350/mm3

    Drug: mefloquine

  • Experimental
    cotrimoxazole (low)

    CD4 cell count\<350/mm3

    Drug: cotrimoxazole

  • Active comparator
    mefloquine & cotrimoxazole

    CD4 cell count\<350/mm3

    Drug: cotrimoxazole · Drug: mefloquine

Interventions

  • Drugcotrimoxazole

    800 mg sulfamethoxazole and 160 mg trimethoprim daily, from 28 weeks of gestation until delivery

  • Drugmefloquine

    mefloquine 15 mg/Kg three times, between 16 and 28 weeks, 24 and 32 weeks, then 28 and 36 weeks of pregnancy

05

What researchers measure

Primary outcomes

  1. proportion of placental malaria (presence of parasites in the placental blood smear at delivery)

    Time frame: delivery

Secondary outcomes

  1. placental malaria mean parasite density at delivery

    Time frame: delivery

  2. proportion of low birth weight infants (<2500 g) and mean birth weight

    Time frame: delivery

  3. proportion of maternal anaemia (<11g/dl) and severe maternal anaemia (<8g/dl) at delivery and during pregnancy

    Time frame: course of pregnancy and delivery

  4. cord blood malaria infection at delivery (infant parasitemia)

    Time frame: delivery

  5. pre-term deliveries (< 37 weeks)

    Time frame: delivery

  6. spontaneous abortions (early:<28 weeks, late: ≥28 weeks) and still births

    Time frame: course of pregnancy

  7. congenital anomalies

    Time frame: first 6 months of life

  8. 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)

  9. Mother-to-child HIV transmission rate in each treatment arm

    Time frame: 2 months after breastfeeding cessation

  10. 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

06

Study locations

5 sites
  • 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, Benin
07

References and documents

Publications

  • 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. PubMed 24996807 ↗
08

Registry details

Key details

Study ID
NCT00970879
Lead sponsor
Institut de Recherche pour le Developpement
Collaborators
Sidaction, Saint Antoine University Hospital, National University Hospital, Cotonou, Université d'Abomey-Calavi, Ministry of Health, Benin
Responsible party
Lise Denoeud-Ndam (MD, MPH, Institut de Recherche pour le Developpement) — Principal investigator
First posted
Sep 3, 2009
Start date
Dec 2009
Primary completion
Jul 2012
Completion
Dec 2012
Last update
Jan 23, 2013

Study contacts

Marcel D Zannou, Professor
principal investigator · Cotonou University Hospital & Faculté des Sciences de la Santé, Benin
Pierre-Marie Girard, Professor
study chair · Saint Antoine Hospital, Assistance Publique-Hôpitaux se Paris
Michel Cot, MD, PHD
study director · Institut de Recherche pour le Developpement

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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