Daily Co-trimoxazole Prophylaxis to Prevent Malaria in Pregnancy

NCT ID: NCT00711906

Last Updated: 2016-01-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 352 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2010-09-30

Brief Summary

Malaria is a major contributor of disease burden in Sub-Saharan Africa, and pregnant women and children are the most vulnerable population. Malaria in pregnancy increases the risks of abortion, prematurity, maternal anaemia, low birth weight (LBW), perinatal, neonatal and infant mortality. For prevention and control of malaria in pregnancy, Intermittent Preventive Treatment (IPT), insecticide treated nets (ITNs) and case management for malaria and anemia are recommended.

HIV infection in pregnancy increases the risk of malaria, LBW, post-natal mortality and also of anaemia. In pregnant women, HIV infection decreases the efficacy of IPT with the medicine sulfadoxine-pyrimethamine (SP), which is the only treatment with proven efficacy and safety in IPT and is recommended by the World Health Organization (WHO). Unfortunately, there is a documented increase of resistance to SP, so cotrimoxazole (CTX) could be an alternative: many studies in Zambia and Uganda demonstrated that it reduces mortality and morbidity in HIV infected persons, and CTX prophylaxis significantly improves birth outcomes in immuno-suppressed HIV women. Unfortunately, there is not yet information on its effectiveness for preventing placental malaria infection, maternal anaemia and LBW. Thus in this study, we aim to establish the safety and efficacy of daily CTX in preventing malaria infection during pregnancy and its consequences, both in HIV infected and non-infected pregnant women. This information is urgently needed to assist to issue guidelines on IPT in pregnancy.

Detailed Description

Malaria is a major contributor of disease burden in Sub-Saharan Africa, with pregnant women and children being the most vulnerable population. P. falciparum infection in pregnancy leads to parasite sequestration in placental vascular space, with increased risks of abortion, stillbirth, prematurity, intrauterine growth retardation, maternal anaemia, low birth weight (LBW), perinatal, neonatal and infant mortality. In low transmission areas, malaria can evolve towards severe disease with high risk of mortality. In endemic areas, it is still associated with maternal anaemia, LBW and stillbirth. For prevention and control of malaria in pregnancy, WHO recommends Intermittent Preventive Treatment (IPT), insecticide treated nets (ITNs) and case management for malaria and anemia.

HIV in pregnancy increases the risk of malaria, LBW, post-natal mortality and also anaemia, suggesting a synergistic interaction between HIV and malaria.

In pregnant women, HIV-1 infection decreases the efficacy of sulfadoxine-pyrimethamine(SP)IPT, although 2 or more doses in 2nd and 3rd trimesters still reduce peripheral parasitaemia, placental infections and maternal anaemia.

To date, SP is the only treatment with data on efficacy and safety in IPT: WHO recommends at least 2 doses after the first trimester. But there is a documented increase in SP resistance, so cotrimoxazole (CTX) could be an alternative: many studies in Zambia and Uganda demonstrated that it reduces mortality and morbidity in HIV infected individuals, and CTX prophylaxis significantly improves birth outcomes in women with CD4 count <200. Concurrent administration of SP and CTX has been associated with increased incidence of severe adverse reactions in HIV-infected patient.

WHO has promoted CTX as alternative to SP for IPT in immuno-compromised HIV-infected pregnant women. Unfortunately, there is no information on effectiveness of daily CTX for preventing placental malaria infection, maternal anaemia and LBW. In the past, CTX has been used to treat malaria in children and daily use of CTX by non-pregnant HIV-infected adults has been associated with a 70% reductions of the incidence of clinical malaria.

In this study, we will target both HIV infected and non-infected pregnant women with CD4≥ 200/µL, with the aim to establish the safety and efficacy of daily CTX in preventing malaria infection during pregnancy and its consequences, by assuming that CTX is not inferior to SP in reducing placental parasitaemia: such information is urgently needed to assist to issue guidelines on IPT in pregnant women.

Conditions

Malaria in Pregnancy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

1

HIV-negative women taking CTX as chemoprophylaxis

Group Type: EXPERIMENTAL

Cotrimoxazole

Intervention Type: DRUG

Cotrimoxazole

2

HIV-negative women taking SP as IPT

Group Type: ACTIVE_COMPARATOR

Sulfadoxine-pyrimethamine

Intervention Type: DRUG

Sulfadoxine-pyrimethamine

3

HIV-positive women (CD4\> 200) taking CTX as chemoprophylaxis

Group Type: EXPERIMENTAL

Cotrimoxazole

Intervention Type: DRUG

Cotrimoxazole

4

HIV-positive women (CD4 \> 200) taking SP as IPT

Group Type: ACTIVE_COMPARATOR

Sulfadoxine-pyrimethamine

Intervention Type: DRUG

Sulfadoxine-pyrimethamine

Interventions

Cotrimoxazole

Cotrimoxazole

Intervention Type: DRUG

Sulfadoxine-pyrimethamine

Sulfadoxine-pyrimethamine

Intervention Type: DRUG

Other Intervention Names

CTX; Bactrim; SP; Fansidar

Eligibility Criteria

Inclusion Criteria

• Confirmed pregnancy (through palpable fundus and/ or positive pregnancy test)
• Gestational age between 16 and 28 weeks.
• Informed consent by patient (or parent/ guardian if patient is less than 18 years of age)
• No symptoms consistent with malaria
• Willingness to deliver at the health facility
• Willingness to adhere to all requirements of the study (including HIV-1 testing)

Exclusion Criteria

• History of allergy to study drugs, or previous history of allergy to sulpha drugs
• History or presence of major illnesses likely to influence pregnancy outcome including diabetes mellitus, severe renal or heart disease, or active tuberculosis, prior to randomization;
• Any significant illness that requires hospitalization;
• Intent to move out of the study catchment's area before delivery or deliver at relative's home out of the catchment's area;
• Prior enrolment in the study or concurrent enrolment in another study
• Severe anaemia (Hb<7 g/dl)
• Previous history of unfavourable pregnancy outcome: pre-eclampsia, caesarean section, stillbirth.
• Being HIV infected and already receiving CTX prophylaxis or ARV treatment

• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Tropical Diseases Research Centre, Zambia

OTHER_GOV

Sponsor Role: collaborator

Institute of Tropical Medicine, Belgium

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christine Manyando, MD

Role: PRINCIPAL_INVESTIGATOR

Tropical Diseases Research Centre

Jean-Pierre Van geertruyden, MD PhD

Role: STUDY_DIRECTOR

Institute of Tropical Medicine

Locations

Choma hospital

Choma, , Zambia

Shampande Clinic

Shampande, , Zambia

Countries

Zambia

References

Pons-Duran C, Wassenaar MJ, Yovo KE, Marin-Carballo C, Briand V, Gonzalez R. Intermittent preventive treatment regimens for malaria in HIV-positive pregnant women. Cochrane Database Syst Rev. 2024 Sep 26;9(9):CD006689. doi: 10.1002/14651858.CD006689.pub3.

Reference Type: DERIVED

PMID: 39324693 (View on PubMed)

Manyando C, Njunju EM, Mwakazanga D, Chongwe G, Mkandawire R, Champo D, Mulenga M, De Crop M, Claeys Y, Ravinetto RM, van Overmeir C, Alessandro UD, Van Geertruyden JP. Safety of daily co-trimoxazole in pregnancy in an area of changing malaria epidemiology: a phase 3b randomized controlled clinical trial. PLoS One. 2014 May 15;9(5):e96017. doi: 10.1371/journal.pone.0096017. eCollection 2014.

Reference Type: DERIVED

PMID: 24830749 (View on PubMed)

Related Links

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0096017;jsessionid=5BFAF926D82FA94E2B41060D2FFBE596

study results

Other Identifiers

ITMP0108

Identifier Type: -

Identifier Source: org_study_id