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 IV

Further Study Details: 

Primary Outcomes: Peripheral parasitemia; Hemoglobin level
Secondary Outcomes: Effect of HIV serostatus on drug efficacy
Expected Total Enrollment:  600

In malaria endemic areas in sub-Saharan Africa, pregnant women, especially primi - and secundigravidae, 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 400 0.4 mg are given for two weeks, and then are replaced by folic acid 5 mg.

Ages Eligible for Study:  15 Years   -   45 Years,  Genders Eligible for Study:  Female

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

Please refer to this study by ClinicalTrials.gov identifier  NCT00130065

Mary Hamel, MD      254-57-20-22902    mhamel@ke.cdc.gov

Kenya
      CDC/Kenya Medical Research Institute, Kisumu,  Kenya; Recruiting

Study chairs or principal investigators

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   

Study ID Numbers:  CDC-NCID-3683
Last Updated:  August 12, 2005
Record first received:  August 12, 2005
ClinicalTrials.gov Identifier:  NCT00130065
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-08-23