MalariaPhase 4NCT00130065
The Effect of Folic Acid on Efficacy of Sulfadoxine-pyrimethamine in Pregnant Women in Western Kenya
A Phase 4 study testing Sulfadoxine-pyrimethamine/folic acid in people with Malaria, run by Centers for Disease Control and Prevention at 1 site in Kenya.
Trial summary
The purpose of this study is to determine whether folic acid, which is often routinely given to pregnant women to prevent birth defects and anemia, affects the efficacy of sulfadoxine-pyrimethamine, another drug that is routinely given to pregnant women in highly malarious areas, for prevention of the adverse effects… Read more about this study
- Who is it for?
- Ages 15 to 45 years, women only
- Conditions the study is for
- Malaria
- What is being tested?
- Sulfadoxine-pyrimethamine/folic acid
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 600 participants
- Where
- 1 siteKenya
- Study dates
- Nov 2003to Feb 2006
- Phase
- Phase 4
- 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 15 to 45 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Parasitemia with a parasite density of ≥ 500 parasites/microliter
- Gestational age > 16 weeks and < 35 weeks
- Willingness to provide blood samples and participate in HIV counseling and testing
- Available for follow up for the entire study period
- Hemoglobin > 7 g/dl
- Age 15-45 years
Who cannot join
- Use of folate in the last 4 weeks
- Gestational age <16 weeks or >35 weeks
- History of an allergy to sulfonamides or other unknown drugs
- Intake of sulfa-containing drugs or 4-aminoquinolones in the previous month
- A urine test positive for sulfa-compounds
- Sickle cell disease
Show all 9Show fewer
- Concomitant diseases needing treatment with co-trimoxazole or other sulfa-containing drug
- Hemoglobin < 7 g/dl
- Severe malaria or any other serious medical condition requiring hospitalization and/or additional treatment. Clinical danger signs of severe malaria include prostration, impaired consciousness, respiratory distress, multiple convulsions, circulatory collapse, pulmonary oedema, abnormal bleeding, jaundice, and hemoglobinuria. Laboratory signs of severe malaria include severe anemia (hemoglobin < 7 g/dl), hypoglycemia, acidosis, hyperlactataemia, hyperparasitaemia (a parasitemia > 100,000 parasites/µl), and renal impairment
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Folic Acid Supplementation on Efficacy of Sulfadoxine-pyrimethamine in Pregnant Women in Western Kenya
The purpose of this study is to determine whether folic acid, which is often routinely given to pregnant women to prevent birth defects and anemia, affects the efficacy of sulfadoxine-pyrimethamine, another drug that is routinely given to pregnant women in highly malarious areas, for prevention of the adverse effects of malaria during pregnancy.
Read the detailed description
In malaria endemic areas in sub-Saharan Africa, pregnant women, especially primi- and secundi-gravidae, are more likely to have placental and peripheral parasitemia with Plasmodium falciparum than non-pregnant women. Adverse consequences of malaria in pregnancy include maternal anemia, and low birth weight of the new born. Low birth weight is known to be the most important risk factor for infant mortality.
Intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) during pregnancy can mitigate the adverse effects of malaria in pregnancy and is the current standard of care in areas of high malaria transmission in sub-Saharan Africa, as recommended by the World Health Organization.
SP acts by inhibiting parasite enzymes in the metabolism of folic acid. However, in vitro studies indicate that folic acid can antagonize the antimalarial parasite activity of SP. Furthermore, in one West African study, supplementary folic acid compromised the antimalarial efficacy of SP in children with acute malaria aged 6 months to 12 years.
Folic acid requirements are increased during pregnancy, and supplementation with folic acid in pregnancy is recommended. Although in most countries a daily supplementation of 400 to 600 micrograms is considered sufficient, for logistical reasons the daily recommended dose in Kenya is 5 mg of folic acid during pregnancy. It is unknown whether folic acid supplementation might compromise the efficacy of IPT with SP in pregnant women living in malaria endemic areas.
Several studies have shown that HIV-seropositive pregnant women have a higher risk of malaria than HIV-seronegative pregnant women. In addition, HIV-infected women are more likely to be anemic compared with HIV-uninfected women. A few studies have also shown that HIV-seropositive women do not appear to respond as well to IPT with SP compared to HIV-seronegative pregnant women.
In a recent study in pregnant women in Zimbabwe, HIV-infection was a negative predictor of serum folate, and the authors suggested this may be because of reduced intake and absorption, and increased catabolism in HIV-infected pregnant women. Because HIV-seropositive women as a group may have a different folic acid status (and a potential different reaction to folic acid supplementation) than HIV-seronegative women, it is important to assess HIV-status in study participants. It is also important to confirm that no difference exists between HIV-seropositive and HIV-seronegative women in efficacy of SP for clearance of peripheral parasitemia.
Comparison: Parasitemic pregnant women are randomized to receive either SP with folic acid 5 mg, or SP with folic acid 0.4 mg, or SP and placebo. The placebo and the folic acid 0.4 mg are given for two weeks, and then are replaced by folic acid 5 mg.
- Conditions
- Malaria
- Being tested
- Sulfadoxine-pyrimethamine/folic acid, Sulfadoxine-pyrimethamine/placebo
- Keywords
- Malaria, Pregnancy, Sulfadoxine-pyrimethamine, Folic acid, Folate
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sulfadoxine-pyrimethamine/folic acidDrug
Sulfadoxine-pyrimethamine/placeboDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Peripheral parasitemia
Hemoglobin level
Secondary outcomes (1)
Effect of HIV serostatus on drug efficacy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2005 (estimated)
- Study startNov 2003
- Primary completionFeb 2006
- Study completionFeb 2006
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 MalariaStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 600 participants
Sponsor and investigators
- Lead sponsor
- Centers for Disease Control and Prevention
- Sponsor type
- US federal agency
- Collaborators
- Kenya Medical Research Institute, Kenya Ministry of Health
- Responsible party
- Sponsor
- Investigators
- Annemieke Van Eijk, M.D., Ph.D., Principal investigator, Centers for Disease Control and Prevention, Kenya Medical Research InstitiuteMonica Parise, M.D., Principal investigator, Centers for Disease Control and PreventionLaurence Slutsker, M.D., Principal investigator, Centers for Disease Control and Prevention, Kenya Medical Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00130065
- Sponsor's protocol ID
- CDC-NCID-3683
- Other IDs
- UR6-CCU018970
- Status last verified
- Sep 2012
- First submitted
- 12 Aug 2005
- Last updated
- 27 Sep 2012
- Results posted
- No
Publications
Qi YP, Crider KS, Gutman J, Centeno-Tablante E, Fothergill A, Daniels K, Yeung LF, Mai CT, Mehta S, Williams JL, Finkelstein JL. Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas. Cochrane Database Syst Rev. 2026 Feb 18;2(2):CD014217. doi: 10.1002/14651858.CD014217.pub2.
PubMed 41705996van Eijk AM, Ouma PO, Williamson J, Ter Kuile FO, Parise M, Otieno K, Hamel MJ, Ayisi JG, Kariuki S, Kager PA, Slutsker L. Plasma folate level and high-dose folate supplementation predict sulfadoxine-pyrimethamine treatment failure in pregnant women in Western kenya who have uncomplicated malaria. J Infect Dis. 2008 Nov 15;198(10):1550-3. doi: 10.1086/592715.
PubMed 18831691
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Folic Acid Supplementation on Efficacy of Sulfadoxine-pyrimethamine in Pregnant Women in Western Kenya
- ClinicalTrials.gov ID
- NCT00130065
- Acronym / sponsor ID
- CDC-NCID-3683
- Conditions
- Malaria
- Keywords
- Malaria, Pregnancy, Sulfadoxine-pyrimethamine, Folic acid, Folate
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 600 participants
- Lead sponsor
- Centers for Disease Control and PreventionUS federal agency
- Collaborators
- Kenya Medical Research Institute, Kenya Ministry of Health
- Study start
- Nov 2003
- Primary completion
- Feb 2006 (actual)
- Study completion
- Feb 2006 (actual)
- First posted
- 15 Aug 2005 (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.
The purpose of this study is to determine whether folic acid, which is often routinely given to pregnant women to prevent birth defects and anemia, affects the efficacy of sulfadoxine-pyrimethamine, another drug that is routinely given to pregnant women in highly malarious areas, for prevention of the adverse effects of malaria during pregnancy.
Detailed description
In malaria endemic areas in sub-Saharan Africa, pregnant women, especially primi- and secundi-gravidae, are more likely to have placental and peripheral parasitemia with Plasmodium falciparum than non-pregnant women. Adverse consequences of malaria in pregnancy include maternal anemia, and low birth weight of the new born. Low birth weight is known to be the most important risk factor for infant mortality.
Intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) during pregnancy can mitigate the adverse effects of malaria in pregnancy and is the current standard of care in areas of high malaria transmission in sub-Saharan Africa, as recommended by the World Health Organization.
SP acts by inhibiting parasite enzymes in the metabolism of folic acid. However, in vitro studies indicate that folic acid can antagonize the antimalarial parasite activity of SP. Furthermore, in one West African study, supplementary folic acid compromised the antimalarial efficacy of SP in children with acute malaria aged 6 months to 12 years.
Folic acid requirements are increased during pregnancy, and supplementation with folic acid in pregnancy is recommended. Although in most countries a daily supplementation of 400 to 600 micrograms is considered sufficient, for logistical reasons the daily recommended dose in Kenya is 5 mg of folic acid during pregnancy. It is unknown whether folic acid supplementation might compromise the efficacy of IPT with SP in pregnant women living in malaria endemic areas.
Several studies have shown that HIV-seropositive pregnant women have a higher risk of malaria than HIV-seronegative pregnant women. In addition, HIV-infected women are more likely to be anemic compared with HIV-uninfected women. A few studies have also shown that HIV-seropositive women do not appear to respond as well to IPT with SP compared to HIV-seronegative pregnant women.
In a recent study in pregnant women in Zimbabwe, HIV-infection was a negative predictor of serum folate, and the authors suggested this may be because of reduced intake and absorption, and increased catabolism in HIV-infected pregnant women. Because HIV-seropositive women as a group may have a different folic acid status (and a potential different reaction to folic acid supplementation) than HIV-seronegative women, it is important to assess HIV-status in study participants. It is also important to confirm that no difference exists between HIV-seropositive and HIV-seronegative women in efficacy of SP for clearance of peripheral parasitemia.
Comparison: Parasitemic pregnant women are randomized to receive either SP with folic acid 5 mg, or SP with folic acid 0.4 mg, or SP and placebo. The placebo and the folic acid 0.4 mg are given for two weeks, and then are replaced by folic acid 5 mg.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 15 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Parasitemia with a parasite density of ≥ 500 parasites/microliter
- Gestational age > 16 weeks and < 35 weeks
- Willingness to provide blood samples and participate in HIV counseling and testing
- Available for follow up for the entire study period
- Hemoglobin > 7 g/dl
Key exclusion criteria (9 listed)
- Use of folate in the last 4 weeks
- Gestational age <16 weeks or >35 weeks
- History of an allergy to sulfonamides or other unknown drugs
- Intake of sulfa-containing drugs or 4-aminoquinolones in the previous month
- A urine test positive for sulfa-compounds
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 |
|---|---|---|
| Sulfadoxine-pyrimethamine/folic acid | Drug | – |
| Sulfadoxine-pyrimethamine/placebo | Drug | – |
Primary outcome
Peripheral parasitemia
Hemoglobin level
1 secondary outcome
Effect of HIV serostatus on drug efficacy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2012.
- Derived from this study: PubMed 41705996Qi YP, Crider KS, Gutman J, Centeno-Tablante E, Fothergill A, Daniels K, Yeung LF, Mai CT, Mehta S, Williams JL, Finkelstein JL. Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas. Cochrane Database Syst Rev. 2026 Feb 18;2(2):CD014217. doi: 10.1002/14651858.CD014217.pub2.
- Derived from this study: PubMed 18831691van Eijk AM, Ouma PO, Williamson J, Ter Kuile FO, Parise M, Otieno K, Hamel MJ, Ayisi JG, Kariuki S, Kager PA, Slutsker L. Plasma folate level and high-dose folate supplementation predict sulfadoxine-pyrimethamine treatment failure in pregnant women in Western kenya who have uncomplicated malaria. J Infect Dis. 2008 Nov 15;198(10):1550-3. doi: 10.1086/592715.
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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.
Annemieke Van Eijk, M.D., Ph.D. principal investigator
Centers for Disease Control and Prevention, Kenya Medical Research Institiute
Monica Parise, M.D. principal investigator
Centers for Disease Control and Prevention
Laurence Slutsker, M.D. principal investigator
Centers for Disease Control and Prevention, Kenya Medical Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sulfadoxine-pyrimethamine/folic acid in people with Malaria, run by Centers for Disease Control and Prevention at 1 site in Kenya.
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 9 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: finished, as of the sponsor's last update on 27 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Kenya. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Peripheral parasitemia. The study lists 2 primary outcomes in all. 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 NCT00130065, 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 27 Sep 2012.