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

This study has been completed.
Sponsor:
Collaborators:
Kenya Medical Research Institute
Kenya Ministry of Health
Information provided by (Responsible Party):
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT00130065
First received: August 12, 2005
Last updated: September 26, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Malaria
Drug: Sulfadoxine-pyrimethamine/folic acid
Drug: Sulfadoxine-pyrimethamine/placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: The Effect of Folic Acid Supplementation on Efficacy of Sulfadoxine-pyrimethamine in Pregnant Women in Western Kenya

Resource links provided by NLM:


Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:
  • Peripheral parasitemia
  • Hemoglobin level

Secondary Outcome Measures:
  • Effect of HIV serostatus on drug efficacy

Estimated Enrollment: 600
Study Start Date: November 2003
Study Completion Date: February 2006
Primary Completion Date: February 2006 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   15 Years to 45 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00130065

Locations
Kenya
CDC/Kenya Medical Research Institute
Kisumu, Kenya
Sponsors and Collaborators
Kenya Medical Research Institute
Kenya Ministry of Health
Investigators
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
  More Information

No publications provided by Centers for Disease Control and Prevention

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT00130065     History of Changes
Other Study ID Numbers: CDC-NCID-3683, UR6-CCU018970
Study First Received: August 12, 2005
Last Updated: September 26, 2012
Health Authority: United States: Federal Government

Keywords provided by Centers for Disease Control and Prevention:
Malaria
Pregnancy
Sulfadoxine-pyrimethamine
Folic acid
Folate

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Folic Acid
Vitamin B Complex
Fanasil, pyrimethamine drug combination
Sulfadoxine
Pyrimethamine
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Anti-Infective Agents
Anti-Infective Agents, Urinary
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014