Chloroquine for Malaria in Pregnancy

Malaria Clinical Trial

Official title:

A Randomized, Controlled Clinical Trial of Chloroquine as Chemoprophylaxis Versus Intermittent Preventive Therapy to Prevent Malaria in Pregnancy in Malawi

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01443130
• Other study ID #: 09-0112
• Secondary ID: 5U01AI087624-04
• Status: Completed
• Phase: Phase 3
• First received: September 1, 2011
• Last updated: October 1, 2015
• Start date: February 2012
• Est. completion date: January 2015

Study information

• Verified date: May 2015
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Malawi: Ministry of HealthUnited States: Food and Drug AdministrationUnited States: Federal GovernmentUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Description:

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 to cause placental infection, maternal anemia, and low infant birth weight. This is a randomized controlled trial to compare chloroquine as IPT or chloroquine as chemoprophylaxis to IPTp with SP. Women will be randomized after Screening and enrollment, and they begin the assigned treatment between Week 20 and Week 28 gestation. Specimens will be collected at every prenatal visit 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 they are approximately 14 weeks of age. Participants will be randomized to one of the following regimens: Chloroquine approximately 1,500 mg base over 3 days, twice during pregnancy (2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2); Chloroquine base 600 mg (2 tablets) loading dose followed by 300 mg (1 tablet) orally once per week until delivery; SP 1500 mg/75 mg twice during pregnancy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 900
• Est. completion date: January 2015
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A to 99 Years

Eligibility

Inclusion Criteria:

Women who present to the Ndirande Antenatal Clinic (ANC) and meet the following inclusion criteria will be enrolled in the study:

• Before the end of 27th week of gestation

• First or second pregnancy

• Anticipate remaining in Blantyre until 14 weeks after delivery

• Agree to deliver at the Ndirande Health Centre or Queen Elizabeth Central Hospital (QECH)

• Provision of informed consent

Exclusion Criteria:

• Chronic use (>14 days) of any medication with antimalarial or antifolate activity

• Human immunodeficiency virus (HIV) infection

• Known high-risk pregnancy requiring regular supervision of an obstetrician

• Allergy to any of the study drugs

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Malaria

Intervention

Drug:
• Chloroquine
Chloroquine tablets contain 300 mg chloroquine base per tablet. Dosages: Chloroquine 1,500 mg base over 3 days twice during pregnancy or Chloroquine 600 mg loading dose followed by 300 mg orally once per week. Intermittant preventative treatment in pregnancy (IPTp) doses will be administered between weeks 20-28 and weeks 28-34 gestation, 4 weeks apart. Participants randomized to IPTp with chloroquine will require their second and third doses of chloroquine after the initial dose given in the clinic and those assigned to chloroquine chemoprophylaxis will require weekly doses.
• Sulfadoxine-pyrimethamine
Sulfadoxine-pyrimethamine 3 tablets (1,500 mg sulfadoxine and 75 mg pyrimethamine) twice during pregnancy. Intermittant preventive treatment in pregnancy (IPTp) doses will be administered between weeks 20-28 and weeks 28-34, 4 weeks apart.

Locations

Country	Name	City	State
Malawi	Blantyre Malaria Project - Queen Elizabeth Central Hospital	Blantryre	Blantyre

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

Malawi, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Placental Malaria Infection Based on Histology.	The placenta was collected at the time of delivery for examination by histology to determine malaria infection. Malaria infection was concluded if histology identified parasites or malaria pigment in the placental tissue.	At delivery: Approximately 12-36 weeks after enrollment	No
Secondary	Incidence of Placental Malaria by Placental Impression Smear	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.	At delivery: Approximately 12-36 weeks after enrollment	Yes
Secondary	Incidence of Maternal Anemia (Hemoglobin < 10 Grams/Deciliter)	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).	From enrollment until delivery, approximately 12-36 weeks	Yes
Secondary	Incidence of Maternal Severe Anemia (Hemoglobin < 7gm/dl)	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.	From enrollment until delivery, approximately 12-36 weeks	Yes
Secondary	Incidence of Stillbirth	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.	At delivery: Approximately 12-36 weeks after enrollment	Yes
Secondary	Incidence of Miscarriage	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.	At delivery: Approximately 12-36 weeks after enrollment	Yes
Secondary	Incidence of Preterm Delivery	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.	At delivery: Approximately 12-36 weeks after enrollment	Yes
Secondary	Infant Mortality Rate to 14 Weeks of Age	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.	For 14 weeks after delivery.	Yes
Secondary	Incidence of Low Birth Weight (LBW) (Birthweight < 2500 Grams)	Maternal participants were followed to outcome of the pregnancy. The outcome measure provides the incidence of infants whose birthweight was less than 2500 grams.	At delivery: Approximately 12-36 weeks after enrollment	Yes
Secondary	Incidence of Intrauterine Growth Restriction (IUGR) (Weight <10th Percentile Gestational Age Based on the World Health Organization (WHO) Fetal Growth Curve)		At delivery: Approximately 12-36 weeks after enrollment	Yes
Secondary	Incidence of Active Placental Malaria Infection Diagnosed by the Presence of Parasites and/or Pigment on Histological Section.		At delivery: Approximately 12-36 weeks after enrollment	No
Secondary	Incidence of Malaria Infection, All Species.		Enrollment to delivery (approximately 12-36 weeks)	No
Secondary	Incidence of Clinical Malaria, All Species.		Enrollment to delivery (approximately 12-36 weeks)	No
Secondary	Incidence of Infection in the Fetal Circulation Based on the Results of the Thick Smear and PCR From the Cord Blood Sample.		At delivery: Approximately 12-36 weeks after enrollment	No