Clinical Trial: Chloroquine for Malaria in Pregnancy
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Randomized, Controlled Clinical Trial of Chloroquine as Chemoprophylaxis Versus Intermittent Preventive Therapy to Prevent Malaria in Pregnancy in Malawi
Brief Summary: The purpose of this study is to test prevention strategies for pregnancy-related malaria. Researchers will compare different malaria treatments and treatment schedules which include chloroquine therapy (weekly doses versus being dosed twice during pregnancy for 3 days each time) to the standard practice of preventive treatment intervals in pregnancy (with the drug sulfadoxine-pyrimethamine given twice during pregnancy). Participants will include 900 pregnant women, who will be assigned to one of three treatment groups. Blood samples will be collected at every visit before birth and any time the participant is ill to determine if malaria is present. Pregnant women will be monitored during pregnancy and newborns will be assessed at birth and followed until about 14 weeks. Participant involvement in the study is expected to last about 12 months.
Detailed Summary: In areas of high malaria endemicity, typical of much of sub-Saharan Africa, despite having achieved semi-immunity to malaria in adulthood, women become vulnerable to malaria infection during pregnancy, especially during their first or second pregnancy. They have increased rates of infection in the peripheral blood and high concentrations of parasites can be found in the placenta. On histological examination, mature asexual parasites, forms that are not usually detected in the peripheral blood, accumulate in the placenta. Pregnancy-specific variant surface antigens are responsible for the increased vulnerability of pregnant women to malaria because they are unrecognized by the immune systems of women who encounter them for the first time in their first pregnancy. In subsequent pregnancies, women develop immunity to these parasite surface antigens and the parasites are cleared by the host response. Plasmodium (P) falciparum infection during pregnancy has important health consequences for both pregnant women and their newborns. Adverse outcomes of pregnancy-associated malaria that have been documented in Malawi include maternal anemia, low birth weight (LBW), and increased infant mortality. The primary objective of the study is to compare weekly chloroquine prophylaxis and chloroquine intermittent preventative therapy (IPT) for malaria in pregnancy (IPTp) to the standard practice [IPTp with sulfadoxine-pyrimethamine (SP)] with respect to prevention of placental malaria. The secondary objectives are: to compare weekly chloroquine prophylaxis and chloroquine IPTp to the standard practice (IPTp with SP) with respect to prevention of malaria during pregnancy; to compare weekly chloroquine prophylaxis and chloroquine IPTp to the standard practice (IPTp with SP) with respect to prevention of the adverse maternal and newborn effects of pregnancy-associated malaria. The exploratory objective identify the vulnerable periods during pregnancy when malaria infection is more likely
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Current Primary Outcome: Incidence of Placental Malaria Infection Based on Histology [ Time Frame: At delivery: Approximately 12-36 weeks after enrollment ]
Original Primary Outcome: Incidence of Placental Malaria Infection Based on Histology. [ Time Frame: After childbirth (approximately 13-19 weeks after randomization) ]
Current Secondary Outcome:
- Incidence of Placental Malaria by Placental Impression Smear [ Time Frame: At delivery: Approximately 12-36 weeks after enrollment ]Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of malaria infection in the placenta based on diagnosis by positive placental impression smear results.
- Incidence of Maternal Anemia (Hemoglobin < 10 Grams/Deciliter) [ Time Frame: From enrollment until delivery, approximately 12-36 weeks ]Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of anemia among maternal participants during pregnancy . Anemia is defined as having a hemoglobin value less than 10 grams/deciliter (gm/dL).
- Incidence of Maternal Severe Anemia (Hemoglobin < 7gm/dl) [ Time Frame: From enrollment until delivery, approximately 12-36 weeks ]Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of severe anemia among maternal participants during pregnancy. Severe anemia is defined as having a hemoglobin value less than 7 gm/dl.
- Incidence of Stillbirth [ Time Frame: At delivery: Approximately 12-36 weeks after enrollment ]Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of participants' deliveries whose outcome was stillbirth, defined as an infant born without any signs of life at 28 weeks or greater of gestation.
- Incidence of Miscarriage [ Time Frame: At delivery: Approximately 12-36 weeks after enrollment ]Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of participants' deliveries whose outcome was miscarriage, defined as an infant delivered without any signs of life at less than 28 weeks of gestation.
- Incidence of Preterm Delivery [ Time Frame: At delivery: Approximately 12-36 weeks after enrollment ]Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of participants' deliveries whose outcome was preterm delivery, defined as delivery less than 37 weeks of gestation. The outcome of the delivery was not considered, and could have been live birth, stillbirth, or miscarriage.
- Infant Mortality Rate to 14 Weeks of Age [ Time Frame: For 14 weeks after delivery. ]Infants were followed from the time of delivery until 14 weeks of age. This outcome measure provides the incidence of infants who died within 14 weeks of delivery.
- Incidence of Low Birth Weight (LBW) (Birthweight < 2500 Grams) [ Time Frame: At delivery: Approximately 12-36 weeks after enrollment ]Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of infants whose birthweight was less than 2500 grams.
- Incidence of Intrauterine Growth Restriction (IUGR) [ Time Frame: At delivery: Approximately 12-36 weeks after enrollment ]Infants were followed from the time of delivery until 14 weeks of age. This outcome measure provides the incidence of infants with IUGR at delivery. IUGR is defined as weight below the 10th percentile for gestational age based on the World Health Organization (WHO) fetal growth curve. This classification is supported by literature resulting from the INTERGROWTH-21st Project; José Villar.
- Incidence of Active Placental Malaria Infection [ Time Frame: At delivery: Approximately 12-36 weeks after enrollment ]Maternal participants were followed to outcome of the pregnancy. This outcome measure provides the number of placental malaria infections in maternal subjects diagnosed by the presence of parasites and/or pigment on histological section or molecular evidence of infection (PCR).
- Incidence of Malaria Infection, All Species. [ Time Frame: Enrollment to delivery (approximately 12-36 weeks) ]Maternal participants were followed to outcome of the pregnancy. This outcome measure provides the number of malaria infection episodes measured by positive parasitemia in maternal subjects.
- Incidence of Clinical Malaria, All Species [ Time Frame: Enrollment to delivery (approximately 12-36 weeks) ]Maternal participants were followed to outcome of the pregnancy. Clinical malaria is defined as malaria infection at any parasite density with associated symptoms including at least one of the following: objective fever measured at the clinic, history of fever in the past 48 hours or other symptoms in the last 48 hours including: headache, myalgia, vomiting, or weakness.
- Incidence of Infection in the Fetal Circulation [ Time Frame: At delivery: Approximately 12-36 weeks after enrollment ]
Original Secondary Outcome:
- Placental malaria infection diagnosed by placental impression smear. [ Time Frame: After childbirth (approximately 13-19 weeks after randomization) ]
- Incidence of infection in the fetal circulation based on the results of the thick smear and polymerase chain reaction (PCR) from the cord blood sample. [ Time Frame: After childbirth (approximately 13-19 weeks after randomization) ]
- Adverse effects of pregnancy-associated malaria: Maternal anemia including severe, still birth, miscarriage, preterm delivery, low birth weight, intrauterine growth restriction (IUGR), and infant mortality rate to 14 weeks of age. [ Time Frame: Over 7-12 months (duration of study). ]
- Inicidence of active placental malaria infection diagnosed by the presence of parasites and/or pigment on histological section. [ Time Frame: After childbirth (approximately 13-19 weeks after randomization) ]
- Per arm: Incidence of malaria infection, all species. [ Time Frame: Enrollment to delivery (approximately 12-36 weeks) ]
- Per arm: Incidence of clinical malaria, all species. [ Time Frame: Enrollment to delivery (approximately 12-36 weeks) ]
- Per arm: Incidence of sub-microscopic malaria infection, all species. [ Time Frame: Enrollment to delivery (approximately 12-36 weeks) ]
Information By: National Institute of Allergy and Infectious Diseases (NIAID)
Dates:
Date Received: September 1, 2011
Date Started: February 2012
Date Completion:
Last Updated: November 3, 2016
Last Verified: May 2015
