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MalariaPhase 3NCT01443130

Chloroquine for Malaria in Pregnancy

A Phase 3 study testing Chloroquine and Sulfadoxine-pyrimethamine in people with Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Malawi.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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… Read more about this study

Who is it for?
Ages Up to 99 years, women only
Conditions the study is for
Malaria
What is being tested?
Chloroquine and Sulfadoxine-pyrimethamine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
900 participants
Where
1 siteMalawi
Study dates
Feb 2012to Jan 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 99 years
  • Women only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • -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

Trial locations and contacts

1 site in 1 country.

Malawi1 site

  • Blantyre Malaria Project - Queen Elizabeth Central Hospital

    Blantryre, Blantyre

Other trials in Malawi

About this study

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

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.

Read the 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. 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.

Conditions
Malaria
Being tested
Chloroquine, Sulfadoxine-pyrimethamine
Keywords
malaria,Malawi,pregnancy
Medical subject headings
Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ChloroquineDrug

    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-pyrimethamineDrug

    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.

Study groups in NCT01443130
Study groupRoleWhat they receive
Chloroquine IPTExperimental300 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.
Receives: Drug: Chloroquine
Chloroquine ProphylaxisExperimental300 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.
Receives: Drug: Chloroquine
SP IPTActive comparator300 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.
Receives: Drug: Sulfadoxine-pyrimethamine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: At delivery: Approximately 12-36 weeks after enrollment

Secondary outcomes (13)

  1. 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.

    Measured: At delivery: Approximately 12-36 weeks after enrollment

  2. 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).

    Measured: From enrollment until delivery, approximately 12-36 weeks

  3. 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.

    Measured: From enrollment until delivery, approximately 12-36 weeks

  4. 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.

    Measured: At delivery: Approximately 12-36 weeks after enrollment

  5. 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.

    Measured: At delivery: Approximately 12-36 weeks after enrollment

  6. 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.

    Measured: At delivery: Approximately 12-36 weeks after enrollment

  7. 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.

    Measured: For 14 weeks after delivery.

  8. 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.

    Measured: At delivery: Approximately 12-36 weeks after enrollment

  9. Incidence of Intrauterine Growth Restriction (IUGR)

    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.

    Measured: At delivery: Approximately 12-36 weeks after enrollment

  10. Incidence of Active Placental Malaria Infection

    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).

    Measured: At delivery: Approximately 12-36 weeks after enrollment

  11. Incidence of Malaria Infection, All Species.

    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.

    Measured: Enrollment to delivery (approximately 12-36 weeks)

  12. Incidence of Clinical Malaria, All Species

    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.

    Measured: Enrollment to delivery (approximately 12-36 weeks)

  13. Incidence of Infection in the Fetal Circulation

    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.

    Measured: At delivery: Approximately 12-36 weeks after enrollment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Sep 2011 (estimated)
  2. Study startFeb 2012
  3. Primary completionOct 2014
  4. Study completionJan 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
900 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01443130
Sponsor's protocol ID
09-0112
Other IDs
4R01AI104702-04
Status last verified
May 2015
First submitted
1 Sep 2011
Last updated
28 Dec 2016

Publications

  • Buchwald AG, Boudova S, Peterson I, Divala T, Mungwira R, Mawindo P, Gladstone M, Cairo C, Laufer MK. The Association among Malaria in Pregnancy, Neonatal inflammation, and Neurocognitive Development in a Cohort of Malawian Infants. Am J Trop Med Hyg. 2022 Oct 17;107(5):1036-1040. doi: 10.4269/ajtmh.22-0409. Print 2022 Nov 14.

    PubMed 36252805

  • 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.

    PubMed 35057743

  • 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.

    PubMed 35045119

  • 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.

    PubMed 30195996

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Chloroquine and Sulfadoxine-pyrimethamine in people with Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in Malawi.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Malawi. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Oct 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Placental Malaria Infection Based on Histology (time frame: At delivery: Approximately 12-36 weeks after enrollment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01443130, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2016.

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Chloroquine for Malaria in Pregnancy (NCT01443130) | AzTrials