The Effect of Folic Acid on Efficacy of Sulfadoxine-pyrimethamine in Pregnant Women in Western Kenya
|Malaria||Drug: Sulfadoxine-pyrimethamine/folic acid Drug: Sulfadoxine-pyrimethamine/placebo||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Official Title:||The Effect of Folic Acid Supplementation on Efficacy of Sulfadoxine-pyrimethamine in Pregnant Women in Western Kenya|
- Peripheral parasitemia
- Hemoglobin level
- Effect of HIV serostatus on drug efficacy
|Study Start Date:||November 2003|
|Study Completion Date:||February 2006|
|Primary Completion Date:||February 2006 (Final data collection date for primary outcome measure)|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00130065
|CDC/Kenya Medical Research Institute|
|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|