Daily Co-trimoxazole Prophylaxis to Prevent Malaria in Pregnancy

NCT00711906 | Terminated Phase 3

• 1 other identifier: ITMP0108
• Study Type: interventional
• Target: 352
• Locations: 1 country
• Sites: 2

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.

Conditions

Malaria in Pregnancy

Keywords

Malaria; Pregnancy; HIV; Intermittent Preventive Treatment; Safety; Efficacy

Outcome Measures

Primary Outcomes (1)

• To test the hypothesis that co-trimoxazole prophylaxis is not inferior to SP intermittent preventive treatment in preventing placental malaria.

  Pregnancy

Secondary Outcomes (10)

• To evaluate efficacy of CTX prophylaxis in preventing malaria peripheral parasitaemia.

  Pregnancy

• To evaluate efficacy of CTX prophylaxis in preventing perinatal mortality and in improving birth weight

  At birth

• To establish the safety of CTX prophylaxis on the offspring by measuring the gestational age at delivery and birth weight.

  At birth

• To compare the efficacy profile of CTX prophylaxis to that of SP intermittent preventive treatment.

  Pregnancy

• To compare the safety profile of CTX prophylaxis to that of SP intermittent preventive treatment.

  Pregnancy

Study Arms (4)

1

EXPERIMENTAL

HIV-negative women taking CTX as chemoprophylaxis

Drug: Cotrimoxazole

2

ACTIVE COMPARATOR

HIV-negative women taking SP as IPT

Drug: Sulfadoxine-pyrimethamine

3

EXPERIMENTAL

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

Drug: Cotrimoxazole

4

ACTIVE COMPARATOR

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

Drug: Sulfadoxine-pyrimethamine

Interventions

Cotrimoxazole DRUG

Cotrimoxazole

Also known as: CTX, Bactrim

1; 3

Sulfadoxine-pyrimethamine DRUG

Sulfadoxine-pyrimethamine

Also known as: SP, Fansidar

2; 4

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Institute of Tropical Medicine, Belgium: lead
• Tropical Diseases Research Centre, Zambia: collaborator

Study Sites (2)

Choma hospital

Choma, Zambia

Location

Shampande Clinic

Shampande, Zambia

Location

Related Publications (2)

• 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.

  PMID: 39324693 DERIVED

• 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.

  PMID: 24830749 DERIVED

Related Links

• study results

MeSH Terms

Conditions

Malaria

Interventions

Trimethoprim, Sulfamethoxazole Drug Combination; fanasil, pyrimethamine drug combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Christine Manyando, MD

  Tropical Diseases Research Centre

  PRINCIPAL INVESTIGATOR

• Jean-Pierre Van geertruyden, MD PhD

  Institute of Tropical Medicine

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2008
• First Posted: July 9, 2008
• Study Start: February 1, 2009
• Primary Completion: February 1, 2010
• Study Completion: September 1, 2010
• Last Updated: January 18, 2016

Record last verified: 2016-01

Locations

ZA (2)