Chloroquine for Malaria in Pregnancy

NCT01443130 | Completed Phase 3 Results

• 2 other identifiers: 09-01124R01AI104702-04
• Study Type: interventional
• Target: 900
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria

Keywords

malaria,Malawi,pregnancy

Outcome Measures

Primary Outcomes (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.

  At delivery: Approximately 12-36 weeks after enrollment

Secondary Outcomes (13)

• Incidence of Placental Malaria by Placental Impression Smear

  At delivery: Approximately 12-36 weeks after enrollment

• Incidence of Maternal Anemia (Hemoglobin < 10 Grams/Deciliter)

  From enrollment until delivery, approximately 12-36 weeks

• Incidence of Maternal Severe Anemia (Hemoglobin < 7gm/dl)

  From enrollment until delivery, approximately 12-36 weeks

• Incidence of Stillbirth

  At delivery: Approximately 12-36 weeks after enrollment

• Incidence of Miscarriage

  At delivery: Approximately 12-36 weeks after enrollment

Study Arms (3)

Chloroquine IPT

EXPERIMENTAL

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 Prophylaxis

EXPERIMENTAL

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

SP IPT

ACTIVE COMPARATOR

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

Interventions

Chloroquine DRUG

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.

Chloroquine IPT; Chloroquine Prophylaxis

Sulfadoxine-pyrimethamine DRUG

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.

SP IPT

Eligibility Criteria

• Age: Up to 99 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Blantyre Malaria Project - Queen Elizabeth Central Hospital

Blantryre, Blantyre, Malawi

Location

Related Publications (4)

• 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.

  PMID: 36252805 DERIVED

• 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.

  PMID: 35057743 DERIVED

• 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.

  PMID: 35045119 DERIVED

• 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.

  PMID: 30195996 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Chloroquine; fanasil, pyrimethamine drug combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

The observed placental malaria rate was lower than expected causing the study to be under powered. After review of a futility analysis, the Sponsor and DSMB recommended allowing the study to conclude as planned and not to increase the sample size.

Results Point of Contact

• Title: Miriam K. Laufer, MD, MPH
• Organization: University of Maryland School of Medicine

mlaufer@medicine.umaryland.edu

410-706-5333

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2011
• First Posted: September 29, 2011
• Study Start: February 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: January 1, 2015
• Last Updated: December 28, 2016
• Results First Posted: October 29, 2015

Record last verified: 2015-05

Locations

MA (1)