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
  Purpose

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 Intervention Phase
Malaria in Pregnancy
HIV Infections
Drug: cotrimoxazole
Drug: mefloquine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Institut de Recherche pour le Developpement:

Primary Outcome Measures:
  • proportion of placental malaria (presence of parasites in the placental blood smear at delivery) [ Time Frame: delivery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 430
Study Start Date: December 2009
Study Completion Date: December 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00970879

Locations
Benin
Unviversity Hospital Hubert Koutoukou Maga
Cotonou, 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
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
  More Information

No publications provided

Responsible Party: Lise Denoeud-Ndam, MD, MPH, Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier: NCT00970879     History of Changes
Other Study ID Numbers: IRD-Sidaction-01
Study First Received: September 2, 2009
Last Updated: January 21, 2013
Health Authority: Benin: Comité National Provisoire d'Ethique pour la Recherche en Santé

Keywords provided by Institut de Recherche pour le Developpement:
malaria
pregnancy
HIV
prevention
cotrimoxazole
mefloquine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Malaria
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Protozoan Infections
Parasitic Diseases
Mefloquine
Trimethoprim-Sulfamethoxazole Combination
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Infective Agents, Urinary
Renal Agents

ClinicalTrials.gov processed this record on August 19, 2014