- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01443130
Chloroquine for Malaria in Pregnancy
A Randomized, Controlled Clinical Trial of Chloroquine as Chemoprophylaxis Versus Intermittent Preventive Therapy to Prevent Malaria in Pregnancy in Malawi
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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-
Blantyre
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Blantryre, Blantyre, Malawi
- Blantyre Malaria Project - Queen Elizabeth Central Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
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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.
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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.
|
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.
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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.
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Placental Malaria Infection Based on Histology
Time Frame: At delivery: Approximately 12-36 weeks after enrollment
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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.
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At delivery: Approximately 12-36 weeks after enrollment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Placental Malaria by Placental Impression Smear
Time Frame: At delivery: Approximately 12-36 weeks after enrollment
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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.
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At delivery: Approximately 12-36 weeks after enrollment
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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).
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From enrollment until delivery, approximately 12-36 weeks
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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.
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From enrollment until delivery, approximately 12-36 weeks
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Incidence of Stillbirth
Time Frame: At delivery: Approximately 12-36 weeks after enrollment
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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.
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At delivery: Approximately 12-36 weeks after enrollment
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Incidence of Miscarriage
Time Frame: At delivery: Approximately 12-36 weeks after enrollment
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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.
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At delivery: Approximately 12-36 weeks after enrollment
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Incidence of Preterm Delivery
Time Frame: At delivery: Approximately 12-36 weeks after enrollment
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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.
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At delivery: Approximately 12-36 weeks after enrollment
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Infant Mortality Rate to 14 Weeks of Age
Time Frame: For 14 weeks after delivery.
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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.
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For 14 weeks after delivery.
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Incidence of Low Birth Weight (LBW) (Birthweight < 2500 Grams)
Time Frame: At delivery: Approximately 12-36 weeks after enrollment
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Maternal participants were followed to outcome of the pregnancy.
The outcome measure provides the incidence of infants whose birthweight was less than 2500 grams.
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At delivery: Approximately 12-36 weeks after enrollment
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Incidence of Intrauterine Growth Restriction (IUGR)
Time Frame: At delivery: Approximately 12-36 weeks after enrollment
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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.
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At delivery: Approximately 12-36 weeks after enrollment
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Incidence of Active Placental Malaria Infection
Time Frame: At delivery: Approximately 12-36 weeks after enrollment
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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).
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At delivery: Approximately 12-36 weeks after enrollment
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Incidence of Malaria Infection, All Species.
Time Frame: Enrollment to delivery (approximately 12-36 weeks)
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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.
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Enrollment to delivery (approximately 12-36 weeks)
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Incidence of Clinical Malaria, All Species
Time Frame: Enrollment to delivery (approximately 12-36 weeks)
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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.
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Enrollment to delivery (approximately 12-36 weeks)
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Incidence of Infection in the Fetal Circulation
Time Frame: At delivery: Approximately 12-36 weeks after enrollment
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Maternal participants were followed to outcome of the pregnancy.
This outcome measure provides the number of positive for malaria cord blood smear and cord PCR results in maternal subjects based on the results of the thick smear and PCR from the cord blood sample.
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At delivery: Approximately 12-36 weeks after enrollment
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Collaborators and Investigators
Publications and helpful links
General Publications
- Patson N, Mukaka M, Kazembe L, Eijkemans MJC, Mathanga D, Laufer MK, Chirwa T. Comparison of statistical methods for the analysis of recurrent adverse events in the presence of non-proportional hazards and unobserved heterogeneity: a simulation study. BMC Med Res Methodol. 2022 Jan 20;22(1):24. doi: 10.1186/s12874-021-01475-8.
- Patson N, Mukaka M, Peterson I, Divala T, Kazembe L, Mathanga D, Laufer MK, Chirwa T. Effect of adverse events on non-adherence and study non-completion in malaria chemoprevention during pregnancy trial: A nested case control study. PLoS One. 2022 Jan 19;17(1):e0262797. doi: 10.1371/journal.pone.0262797. eCollection 2022.
- Divala TH, Mungwira RG, Mawindo PM, Nyirenda OM, Kanjala M, Ndaferankhande M, Tsirizani LE, Masonga R, Muwalo F, Boudova S, Potter GE, Kennedy J, Goswami J, Wylie BJ, Muehlenbachs A, Ndovie L, Mvula P, Mbilizi Y, Tomoka T, Laufer MK. Chloroquine as weekly chemoprophylaxis or intermittent treatment to prevent malaria in pregnancy in Malawi: a randomised controlled trial. Lancet Infect Dis. 2018 Oct;18(10):1097-1107. doi: 10.1016/S1473-3099(18)30415-8. Epub 2018 Sep 5. Erratum In: Lancet Infect Dis. 2019 Feb;19(2):e39.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Infections
- Vector Borne Diseases
- Parasitic Diseases
- Protozoan Infections
- Malaria
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Amebicides
- Folic Acid Antagonists
- Anti-Infective Agents, Urinary
- Renal Agents
- Chloroquine
- Pyrimethamine
- Sulfadoxine
- Fanasil, pyrimethamine drug combination
Other Study ID Numbers
- 09-0112
- 4R01AI104702-04 (NIH)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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