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

Pregnancy Clinical Trial

— INTREPiD  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05757167
• Other study ID #: Pro00110771
• Secondary ID: 1U01AI162463-01A
• Status: Recruiting
• Phase: Phase 4
• 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
• 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

Related Conditions & MeSH terms

• Birth Weight
• Gestational Age and Weight Conditions
• Low Birthweight
• Malaria
• Malaria in Pregnancy
• Malaria, Falciparum
• Malaria,Falciparum
• Neonatal Health
• Pregnancy
• Premature Birth
• Preterm Birth
• Stillbirth

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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Tuikue Ndam N, Tornyigah B, Dossou AY, Escriou G, Nielsen MA, Salanti A, Issifou S, Massougbodji A, Chippaux JP, Deloron P. Persistent Plasmodium falciparum Infection in Women With an Intent to Become Pregnant as a Risk Factor for Pregnancy-associated Malaria. Clin Infect Dis. 2018 Nov 28;67(12):1890-1896. doi: 10.1093/cid/ciy380. — View Citation

Umbers AJ, Stanisic DI, Ome M, Wangnapi R, Hanieh S, Unger HW, Robinson LJ, Lufele E, Baiwog F, Siba PM, King CL, Beeson JG, Mueller I, Aplin JD, Glazier JD, Rogerson SJ. Does malaria affect placental development? Evidence from in vitro models. PLoS One. 2013;8(1):e55269. doi: 10.1371/journal.pone.0055269. Epub 2013 Jan 31. Erratum In: PLoS One. 2013;8(8). doi:10.1371/annotation/4faa7351-837e-4531-a513-0ea80277017f. — View Citation

Unwin VT, Ahmed R, Noviyanti R, Puspitasari AM, Utami RAS, Trianty L, Lukito T, Syafruddin D, Poespoprodjo JR, Santana-Morales MA, Ter Kuile FO, Adams ER. Use of a highly-sensitive rapid diagnostic test to screen for malaria in pregnancy in Indonesia. Malar J. 2020 Jan 16;19(1):28. doi: 10.1186/s12936-020-3110-6. — View Citation

van Eijk AM, Larsen DA, Kayentao K, Koshy G, Slaughter DEC, Roper C, Okell LC, Desai M, Gutman J, Khairallah C, Rogerson SJ, Hopkins Sibley C, Meshnick SR, Taylor SM, Ter Kuile FO. Effect of Plasmodium falciparum sulfadoxine-pyrimethamine resistance on the effectiveness of intermittent preventive therapy for malaria in pregnancy in Africa: a systematic review and meta-analysis. Lancet Infect Dis. 2019 May;19(5):546-556. doi: 10.1016/S1473-3099(18)30732-1. Epub 2019 Mar 25. — View Citation

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* Note: There are 57 references in all — Click 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

External Links

•   Organization WH. Every Newborn: an action plan to end preventable deaths.
•   WHO. Recommendations on intermittent screening and treatment in pregnancy and the safety of ACTs in the first trimester.