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Phase 3 Completed N=300 Randomized Quadruple-blind Prevention

Reducing the Burden of Malaria in HIV-uninfected Pregnant Women and Infants

Source: ClinicalTrials.gov NCT02163447 ↗
Enrolled (actual)
300
Serious AEs
7.1%
Results posted
Nov 2018
Primary outcomePrimary: Prevalence of Placental Malaria — 49; 30; 26 Participants
◆ Published Evidence
Highly cited
239citations · ~24 / year
Dihydroartemisinin-Piperaquine for the Prevention of Malaria in Pregnancy.
The New England journal of medicine · 2016 · Open access · High-confidence link

Summary

This will be a double-blinded randomized controlled phase III trial of 300 HIV uninfected pregnant women and the children born to them. The study interventions will be divided into two phases. In the first phase, HIV uninfected women at 12-20 weeks gestation will be randomized in equal proportions to one of three intermittent preventive therapy in pregnancy (IPTp) treatment arms: 1) 3 doses of sulfadoxine-pyrimethamine (SP), 2) 3 doses of dihydroartemisinin-piperaquine (DP), or 3) monthly DP. All three interventions arms will have either SP or DP placebo to ensure adequate blinding is achieved. Follow-up for the pregnant women will end approximately 6 weeks after giving birth. In the second phase of the study, all children born to mothers enrolled in the study will be followed from birth until they reach 36 months of age. Children born to mothers randomized to receive 3 doses of SP during pregnancy will receive DP every 3 months between 2-24 months of age. Children born to mothers randomized to receive 3 doses of DP or monthly DP during pregnancy will receive either DP every 3 months or monthly DP between 2-24 months of age. To ensure adequate blinding, children who will receive DP every 3 months will be given DP placebo during the months they will not be taking DP. Children will then be followed an additional year between 24-36 months of age following the interventions. We will test the hypothesis that IPT with DP will significantly reduce the burden of malaria in pregnancy and infancy and improve the development of naturally acquired antimalarial immunity.

Linked Publications (5)

  • Dihydroartemisinin-Piperaquine for the Prevention of Malaria in Pregnancy.
    The New England journal of medicine · 2016 · 239 citations · Open access · High-confidence link
  • Relationships between infection with Plasmodium falciparum during pregnancy, measures of placental malaria, and adverse birth outcomes.
    Malaria journal · 2017 · 79 citations · Open access · High-confidence link
  • Reductions in malaria in pregnancy and adverse birth outcomes following indoor residual spraying of insecticide in Uganda.
    Malaria journal · 2016 · 49 citations · Open access · High-confidence link
  • Impact of Intermittent Preventive Treatment During Pregnancy on Plasmodium falciparum Drug Resistance-Mediating Polymorphisms in Uganda.
    The Journal of infectious diseases · 2017 · 30 citations · Open access · High-confidence link
  • Dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria during pregnancy and risk of malaria in early childhood: A randomized controlled trial.
    PLoS medicine · 2018 · 29 citations · Open access · High-confidence link

Outcome Measures

OutcomeResultp-value
PRIMARY
Prevalence of Placental Malaria
49; 30; 26
PRIMARY
Incidence of Malaria in Pregnant Women
0.95; 0.31; 0
PRIMARY
Incidence of Malaria in Infants
0.87; 0.88; 0.83; 1.24; 0.64
SECONDARY
Number of Participants With Blood Samples Positive for Parasites by Microscopy or LAMP
5; 3; 0; 19; 3; 2
SECONDARY
Number of Participants With Maternal Blood Samples Positive for Parasites by Microscopy and LAMP at Delivery
5; 1; 0; 25; 3; 1
SECONDARY
Number of Participants With One or More Birth Outcomes: Congenital Malformations, Spontaneous Abortion, LBW (<2500g), Still Birth, Pre-term Delivery
19; 19; 9
SECONDARY
Prevalence of Anemia in Pregnant Women
94; 72; 61
SECONDARY
Incidence of Complicated Malaria in Infants
0.022; 0.024; 0.000; 0.035; 0.000
SECONDARY
Incidence of Hospital Admissions in Infants
0.043; 0.036; 0.089; 0.082; 0.043
SECONDARY
Prevalence of Gametocytemia in Pregnant Women
4; 1; 3
SECONDARY
Prevalence of Parasitemia in Infants
59; 25; 7; 52; 4
SECONDARY
Prevalence of Parasitemia at the Time of Monthly Routine Visits During Pregnancy
206; 74; 26
SECONDARY
Prevalence of Gametocytemia in Infants
7; 1; 0; 4; 0

Eligibility Criteria

Inclusion Criteria

  • Pregnancy confirmed by positive urine pregnancy test or intrauterine pregnancy by ultrasound
  • Estimated gestational age between 12-20 weeks
  • Confirmed to be HIV uninfected by rapid test
  • 16 years of age or older
  • Residency within 30km of the study clinic
  • Provision of informed consent by the pregnant woman for herself and her unborn child
  • Agreement to come to the study clinic for any febrile episode or other illness and avoid medications given outside the study protocol
  • Plan to deliver in the hospital

Exclusion Criteria

  • History of serious adverse event to SP or DP
  • Active medical problem requiring inpatient evaluation at the time of screening
  • Intention of moving more than 30km from the study clinic
  • Chronic medical condition requiring frequent medical attention
  • Prior SP preventive therapy or any other antimalarial therapy during this pregnancy
  • Early or active labor (documented by cervical change with uterine contractions)
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02163447) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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