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

Malaria Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00130065
• Other study ID #: CDC-NCID-3683
• Secondary ID: UR6-CCU018970
• Status: Completed
• Phase: Phase 4
• First received: August 12, 2005
• Last updated: September 26, 2012
• Start date: November 2003
• Est. completion date: February 2006

Study information

• Verified date: September 2012
• Source: Centers for Disease Control and Prevention
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical 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 of malaria during pregnancy.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 600
• Est. completion date: February 2006
• Est. primary completion date: February 2006
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 15 Years to 45 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• Sulfadoxine-pyrimethamine/folic acid

• Sulfadoxine-pyrimethamine/placebo

Locations

Country	Name	City	State
Kenya	CDC/Kenya Medical Research Institute	Kisumu

Sponsors (3)

Lead Sponsor	Collaborator
Centers for Disease Control and Prevention	Kenya Medical Research Institute, Kenya Ministry of Health

Country where clinical trial is conducted

Kenya, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peripheral parasitemia
Primary	Hemoglobin level
Secondary	Effect of HIV serostatus on drug efficacy