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

September 26, 2012 updated by: Centers for Disease Control and Prevention

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment

600

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Kenya
      • Kisumu, Kenya
        • CDC/Kenya Medical Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years to 45 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Hemoglobin level
Peripheral parasitemia

Secondary Outcome Measures

Outcome Measure
Effect of HIV serostatus on drug efficacy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centers for Disease Control and Prevention

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2003

Primary Completion (ACTUAL)

February 1, 2006

Study Completion (ACTUAL)

February 1, 2006

Study Registration Dates

First Submitted

August 12, 2005

First Submitted That Met QC Criteria

August 12, 2005

First Posted (ESTIMATE)

August 15, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

September 27, 2012

Last Update Submitted That Met QC Criteria

September 26, 2012

Last Verified

September 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDC-NCID-3683
  • UR6-CCU018970

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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