Chloroquine for Malaria in Pregnancy

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01443130
First received: September 1, 2011
Last updated: September 25, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Malaria
Drug: sulfadoxine/pyrimethamine
Drug: Chloroquine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Randomized, Controlled Clinical Trial of Chloroquine as Chemoprophylaxis Versus Intermittent Preventive Therapy to Prevent Malaria in Pregnancy in Malawi

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Incidence of placental malaria infection based on histology. [ Time Frame: At delivery: Approximately 12-36 weeks after enrollment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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: At delivery: Approximately 12-36 weeks after enrollment ] [ Designated as safety issue: No ]
  • Incidence of maternal anemia (hemoglobin < 10gm/dl) [ Time Frame: From enrollment until delivery, approximately 12-36 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of maternal severe anemia (hemoglobin < 7gm/dl) [ Time Frame: From enrollment until delivery, approximately 12-36 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of stillbirth [ Time Frame: At delivery: Approximately 12-36 weeks after enrollment ] [ Designated as safety issue: Yes ]
  • Incidence of placental malaria infection diagnosed by placental impression smear. [ Time Frame: At delivery: Approximately 12-36 weeks after enrollment ] [ Designated as safety issue: No ]
  • Per arm: Incidence of clinical malaria, all species. [ Time Frame: Enrollment to delivery (approximately 12-36 weeks) ] [ Designated as safety issue: No ]
  • Per arm: Incidence of malaria infection, all species. [ Time Frame: Enrollment to delivery (approximately 12-36 weeks) ] [ Designated as safety issue: No ]
  • Incidence of active placental malaria infection diagnosed by the presence of parasites and/or pigment on histological section. [ Time Frame: At delivery: Approximately 12-36 weeks after enrollment ] [ Designated as safety issue: No ]
  • Infant mortality rate to 14 weeks of age [ Time Frame: For 14 weeks after delivery. ] [ Designated as safety issue: Yes ]
  • Incidence of intrauterine growth restriction (IUGR) (weight <10th percentile gestational age based on the World Health Organization (WHO) fetal growth curve) [ Time Frame: At delivery: Approximately 12-36 weeks after enrollment ] [ Designated as safety issue: Yes ]
  • Incidence of low birth weight (LBW) (birthweight < 2500 grams) [ Time Frame: At delivery: Approximately 12-36 weeks after enrollment ] [ Designated as safety issue: Yes ]
  • Incidence of miscarriage (estimated gestational age <28 weeks) [ Time Frame: At delivery: Approximately 12-36 weeks after enrollment ] [ Designated as safety issue: Yes ]
  • Incidence of preterm delivery [ Time Frame: At delivery: Approximately 12-36 weeks after enrollment ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 900
Study Start Date: February 2012
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chloroquine IPT
300 subjects to receive a therapeutic dose of chloroquine (1,500 mg given over 3 days, 2 tablets on Day 0, 2 tablets on Day 1, 1 tablet on Day 2) will be administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.
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.
Active Comparator: SP IPT
300 subjects to receive a therapeutic dose of sulfadoxine-pyrimethamine (SP), (1500 mg sulfadoxine and 75 mg pyrimethamine (3 tablets)) administered twice during pregnancy at 20-28 weeks and at 28-34 weeks.
Drug: 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.
Experimental: Chloroquine Prophylaxis
300 subjects to receive a loading dose of chloroquine (base) 600 mg (2 tablets) at first administration followed by 300 mg of chloroquine base (1 tablet) every week.
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.

Detailed 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; to compare the effect of IPTp and chemoprophylaxis on the selection of drug-resistant malaria parasites; to identify the vulnerable periods during pregnancy when malaria infection is more likely to cause placental infection, maternal anemia, and low infant birth weight; and to compare the effects of new versus recurrent malaria infections during pregnancy on the risk of developing adverse outcomes in the mother and the infant. 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; SP 1500 mg/75 mg twice during pregnancy.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01443130

Contacts
Contact: Miriam Laufer (410) 706-5333 mlaufer@medicine.umaryland.edu

Locations
Malawi
Blantyre Malaria Project - Queen Elizabeth Central Hospital Recruiting
Blantryre, Blantyre, Malawi
Sponsors and Collaborators
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01443130     History of Changes
Other Study ID Numbers: 09-0112, 5R01AI104702-02
Study First Received: September 1, 2011
Last Updated: September 25, 2014
Health Authority: Malawi: Ministry of Health
United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
malaria, pregnancy, Malawi

Additional relevant MeSH terms:
Malaria
Protozoan Infections
Parasitic Diseases
Fanasil, pyrimethamine drug combination
Pyrimethamine
Sulfadoxine
Chloroquine
Chloroquine diphosphate
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Renal Agents
Amebicides
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Filaricides
Antinematodal Agents

ClinicalTrials.gov processed this record on October 19, 2014