Improving Neonatal Health Through Rapid Malaria Testing in Early Pregnancy With High-Sensitivity Diagnostics

Phase 4

Recruiting

• Conditions: Malaria,Falciparum; Pregnancy; Low Birthweight; Neonatal Health; Stillbirth; Malaria in Pregnancy; Gestational Age and Weight Conditions; Malaria in Childbirth; Preterm Birth
• Interventions: Diagnostic Test: Malaria High-Sensitivity Rapid Diagnostic Test (HS-RDT); Drug: Artemether-lumefantrine (AL)

• Registration Number: NCT05757167
• Lead Sponsor: Duke University

Brief Summary

The purpose of the INTREPiD study is to compare 1st trimester screening for malaria parasites with a high-sensitivity malaria rapid diagnostic test followed by treatment of test-positive women with artemether-lumefantrine (AL) against usual antenatal care on a composite adverse pregnancy outcome including low birth weight, small for gestational age, preterm, fetal loss, or neonatal death.

Detailed Description

INTREPiD is a two-arm, open-label, parallel-assignment randomized trial of a strategy of 1st trimester screening for P. falciparum parasites with a high-sensitivity rapid diagnostic test (HS-RDT). Participants will be women of all gravidities presenting to antenatal clinics in the 1st trimester in sites endemic for P. falciparum malaria in Kenya and the Democratic Republic of the Congo.

Following consent and enrollment, women will be allocated 1:1 to either usual antenatal care or to the intervention. The intervention will be a single screening in the 1st trimester for P. falciparum infection in maternal peripheral blood with a HS-RDT. Women who test positive for P. falciparum on HS-RDT testing will be treated with a single course of Artemether-Lumefantrine (AL) and then returned to usual antenatal care.

Participants will be followed through delivery and then through their offspring's first month of life.

The Hypothesis is that, compared to usual antenatal care, screening women in the 1st trimester for P. falciparum and treating them if positive with AL will reduce the risk of an adverse pregnancy outcome.

Study Timeline

• Study First Submitted: 2023-02-24
• Study First Submitted QC: 2023-02-24
• Study First Posted: 2023-03-07
• Study Start: 2023-11-06
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-15
• Last Update Posted: 2025-05-20
• Primary Completion: 2026-11-30
• Study Completion: 2026-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 2500

Inclusion Criteria

• Aged between 16 years and 40 years (inclusive)
• Viable singleton pregnancy with gestational age estimated less than 13 6/7 weeks (inclusive) by ultrasound
• HIV-uninfected
• Willing to participate in the study schedule
• Planning to remain in the study area for the duration of pregnancy and 1 month after delivery
• Willing to deliver in a study-affiliated health facility

Exclusion Criteria

• High risk pregnancy that requires referral for specialized care by local guidelines
• Active medical problem at the time of screening requiring higher level care
• Antimalarial receipt in the 2 weeks prior to screening
• Past allergy to Artemether or Lumefantrine or another condition that prohibits the receipt of either drug
• Current participation in another clinical research study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HS-RDT screening/AL treatment	Malaria High-Sensitivity Rapid Diagnostic Test (HS-RDT)	Pregnant women will be screened with a malaria HS-RDT and, if positive, treated with artemether-lumefantrine
HS-RDT screening/AL treatment	Artemether-lumefantrine (AL)	Pregnant women will be screened with a malaria HS-RDT and, if positive, treated with artemether-lumefantrine

Primary Outcome Measures

Name	Time	Method
Composite number of adverse pregnancy outcomes	Enrollment to 28 days Post-delivery (including each antenatal care visit)	Adverse pregnancy outcomes defined as low birth weight (\<2500 grams) OR preterm (\< 37 0/7 weeks) OR small for gestational age (GA) (\< 10th percentile weight for GA) OR pregnancy loss, defined as a. spontaneous abortion ( loss \< 22 0/7 weeks gestation) OR b. stillbirth (loss ≥ 22 0/7 weeks gestation) OR neonatal death (livebirth with death prior to the 28th day of life).

Secondary Outcome Measures

Name	Time	Method
Incidence of clinical malaria during pregnancy	Enrollment to Delivery (including each antenatal care visit)	Maternal symptoms with peripheral malaria parasitemia detected by light microscopy or rapid diagnostic test
Mean maternal hemoglobin concentration	Enrollment and Delivery	Maternal hemoglobin (g/dL)
Number of mothers with severe anemia at delivery	Delivery	Maternal Hb concentration ≤ 7 g/dL
Number of stillbirths	Delivery	Pregnancy loss ≥ 22 0/7 weeks gestation
Birthweight	Delivery	Birthweight in grams
Number of infants that are small for gestational age	Delivery	Weight for gestational age \< 10th percentile, livebirth
Number of perinatal deaths	Delivery to 28 days Post-delivery	Late fetal death OR Neonatal death
Preterm	Delivery	\< 37 0/7 weeks, livebirth
Number of early fetal deaths	Delivery	Pregnancy loss 22 0/7 - 27 6/7 weeks gestation
Number of pregnancy losses	Delivery	Spontaneous abortion OR stillbirth
Number of infants with low birthweight	Delivery	\< 2500 grams, livebirth
Number of neonatal deaths	Delivery to 28 days Post-delivery	Before the 28th day of life, livebirth
Number of mothers with anemia at delivery	Delivery	Maternal Hb concentration ≤ 11 g/dL
Number of adverse newborn outcomes	Delivery	low birthweight OR preterm OR small for gestational age
Gestational age (GA)	Delivery	GA at delivery in weeks/days, livebirth
Number of spontaneous abortions	Delivery	Pregnancy loss \< 22 0/7 weeks gestation
Number of late fetal deaths	Delivery	Pregnancy loss ≥ 28 0/7 weeks gestation
Number of mothers with peripheral parasitemia at delivery	Delivery	Maternal peripheral parasitemia at delivery by PCR

Trial Locations

Locations (2)

Kinshasa School of Public Health; 🇨🇩 Kinshasa, Congo, The Democratic Republic of the

Moi University; 🇰🇪 Eldoret, Kenya