Daily Co-trimoxazole Prophylaxis to Prevent Malaria in Pregnancy

This study has been terminated.
(Malaria prev. fell in the study area, so we cannot evaluate the primary endpoint)
Sponsor:
Collaborator:
Tropical Diseases Research Centre, Zambia
Information provided by (Responsible Party):
Institute of Tropical Medicine, Belgium
ClinicalTrials.gov Identifier:
NCT00711906
First received: July 8, 2008
Last updated: June 4, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Malaria in Pregnancy
Drug: Cotrimoxazole
Drug: Sulfadoxine-pyrimethamine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: The Role of Daily Co-trimoxazole Prophylaxis For Prevention of Malaria And Its Effects in Pregnancy

Resource links provided by NLM:


Further study details as provided by Institute of Tropical Medicine, Belgium:

Primary Outcome Measures:
  • To test the hypothesis that co-trimoxazole prophylaxis is not inferior to SP intermittent preventive treatment in preventing placental malaria. [ Time Frame: Pregnancy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate efficacy of CTX prophylaxis in preventing malaria peripheral parasitaemia. [ Time Frame: Pregnancy ] [ Designated as safety issue: No ]
  • To evaluate efficacy of CTX prophylaxis in preventing perinatal mortality and in improving birth weight [ Time Frame: At birth ] [ Designated as safety issue: Yes ]
  • To establish the safety of CTX prophylaxis on the offspring by measuring the gestational age at delivery and birth weight. [ Time Frame: At birth ] [ Designated as safety issue: Yes ]
  • To compare the efficacy profile of CTX prophylaxis to that of SP intermittent preventive treatment. [ Time Frame: Pregnancy ] [ Designated as safety issue: No ]
  • To compare the safety profile of CTX prophylaxis to that of SP intermittent preventive treatment. [ Time Frame: Pregnancy ] [ Designated as safety issue: Yes ]
  • Spontaneous abortion [ Time Frame: </=28 weeks gestation ] [ Designated as safety issue: Yes ]
  • Pre-term delivery [ Time Frame: <37 completed weeks ] [ Designated as safety issue: Yes ]
  • Neonatal mortality [ Time Frame: Within 28 days after birth ] [ Designated as safety issue: Yes ]
  • Maternal mortality [ Time Frame: Up to 6 weeks following delivery ] [ Designated as safety issue: Yes ]
  • Major and minor birth defects [ Time Frame: At birth and up to 6 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 352
Study Start Date: February 2009
Study Completion Date: September 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
HIV-negative women taking CTX as chemoprophylaxis
Drug: Cotrimoxazole
Cotrimoxazole
Other Names:
  • CTX
  • Bactrim
Active Comparator: 2
HIV-negative women taking SP as IPT
Drug: Sulfadoxine-pyrimethamine
Sulfadoxine-pyrimethamine
Other Names:
  • SP
  • Fansidar
Experimental: 3
HIV-positive women (CD4> 200) taking CTX as chemoprophylaxis
Drug: Cotrimoxazole
Cotrimoxazole
Other Names:
  • CTX
  • Bactrim
Active Comparator: 4
HIV-positive women (CD4 > 200) taking SP as IPT
Drug: Sulfadoxine-pyrimethamine
Sulfadoxine-pyrimethamine
Other Names:
  • SP
  • Fansidar

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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  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: NCT00711906

Locations
Zambia
Choma hospital
Choma, Zambia
Shampande Clinic
Shampande, Zambia
Sponsors and Collaborators
Institute of Tropical Medicine, Belgium
Tropical Diseases Research Centre, Zambia
Investigators
Principal Investigator: Christine Manyando, MD Tropical Diseases Research Centre
Study Director: Jean-Pierre Van geertruyden, MD PhD Institute of Tropical medicine
  More Information

Additional Information:
No publications provided by Institute of Tropical Medicine, Belgium

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Institute of Tropical Medicine, Belgium
ClinicalTrials.gov Identifier: NCT00711906     History of Changes
Other Study ID Numbers: ITMP0108
Study First Received: July 8, 2008
Last Updated: June 4, 2014
Health Authority: Zambia: Pharmaceutical Regulatory Authority

Keywords provided by Institute of Tropical Medicine, Belgium:
Malaria
Pregnancy
HIV
Intermittent Preventive Treatment
Safety
Efficacy

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Pyrimethamine
Sulfadoxine
Trimethoprim-Sulfamethoxazole Combination
Sulfadoxine-pyrimethamine
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Renal Agents

ClinicalTrials.gov processed this record on July 23, 2014