Prevention of Pregnancy-associated Malaria in HIV-infected Women: Cotrimoxazole Prophylaxis Versus Mefloquine (PACOME)
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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 |
- proportion of placental malaria (presence of parasites in the placental blood smear at delivery) [ Time Frame: delivery ] [ Designated as safety issue: No ]
- 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 |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00970879
| 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, 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 |
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:
|
Malaria Parasitic Diseases Protozoan Infections Mefloquine Trimethoprim-Sulfamethoxazole Combination Anti-Infective Agents Anti-Infective Agents, Urinary |
Antimalarials Antiparasitic Agents Antiprotozoal Agents Pharmacologic Actions Renal Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on February 27, 2015