Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Effect of Folic Acid on Efficacy of Sulfadoxine-pyrimethamine in Pregnant Women in Western Kenya

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00130065
Recruitment Status : Completed
First Posted : August 15, 2005
Last Update Posted : September 27, 2012
Sponsor:
Collaborators:
Kenya Medical Research Institute
Kenya Ministry of Health
Information provided by (Responsible Party):
Centers for Disease Control and Prevention

Tracking Information
First Submitted Date  ICMJE August 12, 2005
First Posted Date  ICMJE August 15, 2005
Last Update Posted Date September 27, 2012
Study Start Date  ICMJE November 2003
Actual Primary Completion Date February 2006   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 12, 2005)
  • Peripheral parasitemia
  • Hemoglobin level
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 12, 2005)
Effect of HIV serostatus on drug efficacy
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effect of Folic Acid on Efficacy of Sulfadoxine-pyrimethamine in Pregnant Women in Western Kenya
Official Title  ICMJE The Effect of Folic Acid Supplementation on Efficacy of Sulfadoxine-pyrimethamine in Pregnant Women in Western Kenya
Brief 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 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Condition  ICMJE Malaria
Intervention  ICMJE
  • Drug: Sulfadoxine-pyrimethamine/folic acid
  • Drug: Sulfadoxine-pyrimethamine/placebo
Study Arms  ICMJE Not Provided
Publications * van 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE
 (submitted: August 12, 2005)
600
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE February 2006
Actual Primary Completion Date February 2006   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 15 Years to 45 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Kenya
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00130065
Other Study ID Numbers  ICMJE CDC-NCID-3683
UR6-CCU018970
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Centers for Disease Control and Prevention
Study Sponsor  ICMJE Centers for Disease Control and Prevention
Collaborators  ICMJE
  • Kenya Medical Research Institute
  • Kenya Ministry of Health
Investigators  ICMJE
Principal Investigator: Annemieke Van Eijk, M.D., Ph.D. Centers for Disease Control and Prevention, Kenya Medical Research Institiute
Principal Investigator: Monica Parise, M.D. Centers for Disease Control and Prevention
Principal Investigator: Laurence Slutsker, M.D. Centers for Disease Control and Prevention, Kenya Medical Research Institute
PRS Account Centers for Disease Control and Prevention
Verification Date September 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP