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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05757167
Other study ID # Pro00110771
Secondary ID 1U01AI162463-01A
Status Recruiting
Phase Phase 4
First received
Last updated
Start date November 6, 2023
Est. completion date April 2026

Study information

Verified date January 2024
Source Duke University
Contact Stephen James, MPH
Phone 919-668-0420
Email stephen.james@duke.edu
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 2500
Est. completion date April 2026
Est. primary completion date April 2026
Accepts healthy volunteers No
Gender Female
Age group 16 Years to 40 Years
Eligibility 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


Intervention

Diagnostic Test:
Malaria High-Sensitivity Rapid Diagnostic Test (HS-RDT)
Detection of Plasmodium falciparum HRP-II antigen1 Method: Lateral Flow; Time to Result: 20 minutes; Sample Type: Fingerstick Whole Blood; Sample Volume: 5µl; Storage Conditions: 1-30°C; Shelf Life: 12 months; Sensitivity/Specificity: 99.0%/98.6%
Drug:
Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet
oral tablets: 6 doses of 80/480 mg over 3 days

Locations

Country Name City State
Congo, The Democratic Republic of the Kinshasa School of Public Health Kinshasa
Kenya Moi University Eldoret

Sponsors (2)

Lead Sponsor Collaborator
Duke University National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

Congo, The Democratic Republic of the,  Kenya, 

References & Publications (57)

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Ballard SB, Salinger A; MPHc; Arguin PM, Desai M, Tan KR. Updated CDC Recommendations for Using Artemether-Lumefantrine for the Treatment of Uncomplicated Malaria in Pregnant Women in the United States. MMWR Morb Mortal Wkly Rep. 2018 Apr 13;67(14):424-431. doi: 10.15585/mmwr.mm6714a4. — View Citation

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Clark RL, Youreneff M, DeLise AM. Developmental toxicity studies of lumefantrine and artemether in rats and rabbits. Birth Defects Res B Dev Reprod Toxicol. 2016 Dec;107(6):243-257. doi: 10.1002/bdrb.21189. — View Citation

Clark RL. Animal Embryotoxicity Studies of Key Non-Artemisinin Antimalarials and Use in Women in the First Trimester. Birth Defects Res. 2017 Aug 15;109(14):1075-1126. doi: 10.1002/bdr2.1035. Epub 2017 Jun 24. Erratum In: Birth Defects Res. 2017 Nov 15;109 (19):1605. — View Citation

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Desai M, Gutman J, L'lanziva A, Otieno K, Juma E, Kariuki S, Ouma P, Were V, Laserson K, Katana A, Williamson J, ter Kuile FO. Intermittent screening and treatment or intermittent preventive treatment with dihydroartemisinin-piperaquine versus intermittent preventive treatment with sulfadoxine-pyrimethamine for the control of malaria during pregnancy in western Kenya: an open-label, three-group, randomised controlled superiority trial. Lancet. 2015 Dec 19;386(10012):2507-19. doi: 10.1016/S0140-6736(15)00310-4. Epub 2015 Sep 28. — View Citation

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* Note: There are 57 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Other Number of maternal serious adverse events Serious adverse events in the mothers Enrollment to 28 days Post-delivery
Other Number of infants with congenital malformations Congenital malformations identified within the first 28 days of birth Delivery to 28 days Post-delivery
Other Number of offspring with the need for hospitalization or acute medical evaluation Hospitalization or acute medical evaluation within the first 28 days of life Delivery to 28 days Post-delivery
Primary Composite number of adverse pregnancy outcomes 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). Enrollment to 28 days Post-delivery (including each antenatal care visit)
Secondary Birthweight Birthweight in grams Delivery
Secondary Number of infants with low birthweight < 2500 grams, livebirth Delivery
Secondary Gestational age (GA) GA at delivery in weeks/days, livebirth Delivery
Secondary Preterm < 37 0/7 weeks, livebirth Delivery
Secondary Number of infants that are small for gestational age Weight for gestational age < 10th percentile, livebirth Delivery
Secondary Number of adverse newborn outcomes low birthweight OR preterm OR small for gestational age Delivery
Secondary Number of spontaneous abortions Pregnancy loss < 22 0/7 weeks gestation Delivery
Secondary Number of stillbirths Pregnancy loss = 22 0/7 weeks gestation Delivery
Secondary Number of early fetal deaths Pregnancy loss 22 0/7 - 27 6/7 weeks gestation Delivery
Secondary Number of late fetal deaths Pregnancy loss = 28 0/7 weeks gestation Delivery
Secondary Number of pregnancy losses Spontaneous abortion OR stillbirth Delivery
Secondary Number of neonatal deaths Before the 28th day of life, livebirth Delivery to 28 days Post-delivery
Secondary Number of perinatal deaths Late fetal death OR Neonatal death Delivery to 28 days Post-delivery
Secondary Incidence of clinical malaria during pregnancy Maternal symptoms with peripheral malaria parasitemia detected by light microscopy or rapid diagnostic test Enrollment to Delivery (including each antenatal care visit)
Secondary Number of mothers with peripheral parasitemia at delivery Maternal peripheral parasitemia at delivery by PCR Delivery
Secondary Mean maternal hemoglobin concentration Maternal hemoglobin (g/dL) Enrollment and Delivery
Secondary Number of mothers with anemia at delivery Maternal Hb concentration = 11 g/dL Delivery
Secondary Number of mothers with severe anemia at delivery Maternal Hb concentration = 7 g/dL Delivery
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