Malaria in PregnancyPhase 3NCT00711906
Daily Co-trimoxazole Prophylaxis to Prevent Malaria in Pregnancy
A Phase 3 study testing Cotrimoxazole and Sulfadoxine-pyrimethamine in people with Malaria in Pregnancy, run by Institute of Tropical Medicine, Belgium at 2 sites in Zambia.
Trial 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. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Malaria in Pregnancy
- What is being tested?
- Cotrimoxazole and Sulfadoxine-pyrimethamine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 352 participants
- Where
- 2 sitesZambia
- Study dates
- Feb 2009to Sep 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: The Role of Daily Co-trimoxazole Prophylaxis For Prevention of Malaria And Its Effects in Pregnancy
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.
Read the 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
- Being tested
- Cotrimoxazole, Sulfadoxine-pyrimethamine
- Keywords
- Malaria, Pregnancy, HIV, Intermittent Preventive Treatment, Safety, Efficacy
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CotrimoxazoleDrug
Also called CTX, Bactrim
Cotrimoxazole
Sulfadoxine-pyrimethamineDrug
Also called SP, Fansidar
Sulfadoxine-pyrimethamine
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | HIV-negative women taking CTX as chemoprophylaxis Receives: Drug: Cotrimoxazole |
| 2 | Active comparator | HIV-negative women taking SP as IPT Receives: Drug: Sulfadoxine-pyrimethamine |
| 3 | Experimental | HIV-positive women (CD4> 200) taking CTX as chemoprophylaxis Receives: Drug: Cotrimoxazole |
| 4 | Active comparator | HIV-positive women (CD4 > 200) taking SP as IPT Receives: Drug: Sulfadoxine-pyrimethamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To test the hypothesis that co-trimoxazole prophylaxis is not inferior to SP intermittent preventive treatment in preventing placental malaria.
Measured: Pregnancy
Secondary outcomes (10)
To evaluate efficacy of CTX prophylaxis in preventing malaria peripheral parasitaemia.
Measured: Pregnancy
To evaluate efficacy of CTX prophylaxis in preventing perinatal mortality and in improving birth weight
Measured: At birth
To establish the safety of CTX prophylaxis on the offspring by measuring the gestational age at delivery and birth weight.
Measured: At birth
To compare the efficacy profile of CTX prophylaxis to that of SP intermittent preventive treatment.
Measured: Pregnancy
To compare the safety profile of CTX prophylaxis to that of SP intermittent preventive treatment.
Measured: Pregnancy
Spontaneous abortion
Measured: </=28 weeks gestation
Pre-term delivery
Measured: <37 completed weeks
Neonatal mortality
Measured: Within 28 days after birth
Maternal mortality
Measured: Up to 6 weeks following delivery
Major and minor birth defects
Measured: At birth and up to 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2008 (estimated)
- Study startFeb 2009
- Primary completionFeb 2010
- Study completionSep 2010
Why it stopped: Malaria prev. fell in the study area, so we cannot evaluate the primary endpoint
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Malaria in PregnancyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 352 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Tropical Medicine, Belgium
- Sponsor type
- University, hospital or other
- Collaborators
- Tropical Diseases Research Centre, Zambia
- Responsible party
- Sponsor
- Investigators
- Christine Manyando, MD, Principal investigator, Tropical Diseases Research CentreJean-Pierre Van geertruyden, MD PhD, Study director, Institute of Tropical Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00711906
- Sponsor's protocol ID
- ITMP0108
- Status last verified
- Jan 2016
- First submitted
- 8 Jul 2008
- Last updated
- 18 Jan 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 39324693Manyando 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.
PubMed 24830749
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Daily Co-trimoxazole Prophylaxis For Prevention of Malaria And Its Effects in Pregnancy
- ClinicalTrials.gov ID
- NCT00711906
- Acronym / sponsor ID
- ITMP0108
- Conditions
- Malaria in Pregnancy
- Keywords
- Malaria, Pregnancy, HIV, Intermittent Preventive Treatment, Safety, Efficacy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Malaria prev. fell in the study area, so we cannot evaluate the primary endpoint
- Enrolment
- 352 participants (actual)
- Lead sponsor
- Institute of Tropical Medicine, BelgiumUniversity, hospital or other
- Collaborators
- Tropical Diseases Research Centre, Zambia
- Study start
- Feb 2009
- Primary completion
- Feb 2010 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 9 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: CotrimoxazoleHIV-negative women taking CTX as chemoprophylaxis |
| 2 | Active comparator | Drug: Sulfadoxine-pyrimethamineHIV-negative women taking SP as IPT |
| 3 | Experimental | Drug: CotrimoxazoleHIV-positive women (CD4> 200) taking CTX as chemoprophylaxis |
| 4 | Active comparator | Drug: Sulfadoxine-pyrimethamineHIV-positive women (CD4 > 200) taking SP as IPT |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CotrimoxazoleAlso: CTX, BactrimCotrimoxazole | Drug | 1, 3 |
| Sulfadoxine-pyrimethamineAlso: SP, FansidarSulfadoxine-pyrimethamine | Drug | 2, 4 |
Primary outcome
To test the hypothesis that co-trimoxazole prophylaxis is not inferior to SP intermittent preventive treatment in preventing placental malaria.
Time frame: Pregnancy
10 secondary outcomes
To evaluate efficacy of CTX prophylaxis in preventing malaria peripheral parasitaemia.
Time frame: Pregnancy
To evaluate efficacy of CTX prophylaxis in preventing perinatal mortality and in improving birth weight
Time frame: At birth
To establish the safety of CTX prophylaxis on the offspring by measuring the gestational age at delivery and birth weight.
Time frame: At birth
To compare the efficacy profile of CTX prophylaxis to that of SP intermittent preventive treatment.
Time frame: Pregnancy
To compare the safety profile of CTX prophylaxis to that of SP intermittent preventive treatment.
Time frame: Pregnancy
Spontaneous abortion
Time frame: </=28 weeks gestation
Pre-term delivery
Time frame: <37 completed weeks
Neonatal mortality
Time frame: Within 28 days after birth
Maternal mortality
Time frame: Up to 6 weeks following delivery
Major and minor birth defects
Time frame: At birth and up to 6 weeks
Results and safety
The study was stopped early (reason given: Malaria prev. fell in the study area, so we cannot evaluate the primary endpoint). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2016.
- Derived from this study: PubMed 39324693Pons-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.
- Derived from this study: PubMed 24830749Manyando 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.
- study resultsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christine Manyando, MD principal investigator
Tropical Diseases Research Centre
Jean-Pierre Van geertruyden, MD PhD study director
Institute of Tropical Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cotrimoxazole and Sulfadoxine-pyrimethamine in people with Malaria in Pregnancy, run by Institute of Tropical Medicine, Belgium at 2 sites in Zambia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Zambia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Malaria prev. fell in the study area, so we cannot evaluate the primary endpoint). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To test the hypothesis that co-trimoxazole prophylaxis is not inferior to SP intermittent preventive treatment in preventing placental malaria. (time frame: Pregnancy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00711906, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2016.