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

Sponsor:	Institut de Recherche pour le Developpement
Collaborators:	Sidaction Saint Antoine University Hospital National University Hospital, Cotonou Faculté des Sciences de la Santé, Benin Institut des Sciences Biomédicales Appliquées, Benin Programme National de Lutte contre le Sida Benin
Information provided by:	Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier:	NCT00970879

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 III

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
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:

MedlinePlus related topics: AIDS AIDS and Pregnancy Malaria

Drug Information available for: Mefloquine hydrochloride Mefloquine Trimethoprim-sulfamethoxazole combination

U.S. FDA Resources

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 ]

Estimated Enrollment:	492
Study Start Date:	October 2009
Estimated Study Completion Date:	October 2012
Estimated Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
cotrimoxazole (high): Experimental CD4 cell count≥350/mm3	Drug: cotrimoxazole 800 mg sulfamethoxazole and 160 mg trimethoprim daily, from 28 weeks of gestation until delivery
mefloquine: Active Comparator 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
cotrimoxazole (low): Experimental CD4 cell count<350/mm3	Drug: cotrimoxazole 800 mg sulfamethoxazole and 160 mg trimethoprim daily, from 28 weeks of gestation until delivery
mefloquine & cotrimoxazole: Active Comparator 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.

We aim to evaluate the efficacy of cotrimoxazole prophylaxis in prevention of malaria during pregnancy in HIV-infected women. We postulate that cotrimoxazole prophylaxis is not inferior to IPT in all women, unrelated to their CD4 cell count. In the control arm, we 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

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

Contacts

Contact: Lise Denoeud-NDAM, MD, MPH	0022921309021	lise.denoeud-ndam@ird.fr
Contact: Michel COT, MD, PHD	0033153739621	michel.cot@ird.fr

Locations

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

Sponsors and Collaborators

Institut de Recherche pour le Developpement

Sidaction

Saint Antoine University Hospital

National University Hospital, Cotonou

Faculté des Sciences de la Santé, Benin

Institut des Sciences Biomédicales Appliquées, Benin

Programme National de Lutte contre le Sida 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:	IRD, UR010 ( Dr Michel Cot )
Study ID Numbers:	IRD-Sidaction-01
Study First Received:	September 2, 2009
Last Updated:	September 2, 2009
ClinicalTrials.gov Identifier:	NCT00970879 History of Changes
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:

Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Antiprotozoal Agents
Slow Virus Diseases
Malaria
Trimethoprim-Sulfamethoxazole Combination
Renal Agents
Infection
Antimalarials
Antiparasitic Agents
Therapeutic Uses
Parasitic Diseases
Mefloquine

Retroviridae Infections
Protozoan Infections
RNA Virus Infections
Immune System Diseases
Coccidiosis
Acquired Immunodeficiency Syndrome
Anti-Infective Agents, Urinary
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on February 04, 2010