Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202302536807007 Date of Approval: 28/02/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Improving Neonatal Health Through Rapid Malaria Testing in Early Pregnancy With High-Sensitivity Diagnostics (INTREPiD)
Official scientific title Improving Neonatal Health Through Rapid Malaria Testing in Early Pregnancy With High-Sensitivity Diagnostics (INTREPiD)
Brief summary describing the background and objectives of the trial Newborn health has improved globally but there remains a critical need in resource-limited settings to reduce neonatal mortality. Nearly all infant deaths in sub-Saharan Africa occur in babies that are small or low birthweight, which often result from antenatal infections with Plasmodium falciparum. These malaria effects can be partially mitigated by pregnancy-specific measures including the administration of monthly antenatal doses of sulfadoxine-pyrimethamine as intermittent preventive therapy during pregnancy (IPTp-SP). These are not typically implemented until the 2nd trimester, and so do not mitigate the risks 1st trimester infections, which result from parasite persistence from the prenatal period or parasite acquisition during the 1st trimester. It is now feasible to include 1st trimester screening for malaria parasites owing to: i) updated WHO guidelines that recommend an expended schedule of 8 ANC contacts, with the first prior to 12 weeks gestation, ii) the availability of high-sensitivity malaria rapid diagnostic tests (HS-RDT) with enhanced detection of low-density infections, and iii) accumulated safety data that enable the use of Artemether-Lumefantrine (AL) for malaria treatment in the 1st trimester. Collectively, these developments enable new strategies to intercept malaria parasites during early pregnancy and improve pregnancy outcomes. 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.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) INTREPiD
Disease(s) or condition(s) being studied Infections and Infestations,Pregnancy and Childbirth
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Early detection /Screening
Anticipated trial start date 01/04/2023
Actual trial start date 06/11/2023
Anticipated date of last follow up 30/11/2025
Actual Last follow-up date 30/06/2025
Anticipated target sample size (number of participants) 2500
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
220009 NIH DMID
Pro00110771 Duke Health Institutional Review Board
0004319 Moi University Institutional Research and Ethics Committee
7472022 Kinshasa School of Public Health
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Central randomisation by phone/fax Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Testing in the 1st trimester with a malaria HsRdt One time Once Testing by malaria Hs Rdt followed by treatment with Artemether-Lumefantrine if positive 1250
Control Group Standard ANC During ANC Standard ANC maneuvers 1250 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• 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 • 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 Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year 16 Year(s) 40 Year(s) Female
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 25/09/2022 Duke Health IRB
Ethics Committee Address
Street address City Postal code Country
2424 Erwin Rd Durham 27705 United States of America
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 10/01/2023 Moi University IREC
Ethics Committee Address
Street address City Postal code Country
Po Box 3 Eldoret none Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 25/10/2022 Kinshasa School of Public Health Comite dEthique
Ethics Committee Address
Street address City Postal code Country
BP 11850 Kin I Kinshasa 11850 Democratic Republic of the Congo
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome • 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) at the conclusion of pregnancy or 28d after livebirth
Secondary Outcome Birthweight in grams Delivery
Secondary Outcome Low birthweight less than 2500g Delivery
Secondary Outcome Gestational age in weeks-days Delivery
Secondary Outcome Preterm less than 37 0/7 weeks Delivery
Secondary Outcome Small for gestational age less than 10th percentile Delivery
Secondary Outcome Adverse newborn outcome low birthweight or preterm or small for gestational age Delivery
Secondary Outcome Spontaneous abortion defined as pregnancy loss less than 22 0/7 weeks gestation 22 0/7 weeks gestation
Secondary Outcome Stillbirth defined as pregnancy loss greater than or equal to 22 0/7 weeks gestation Delivery
Secondary Outcome Early fetal death defined as pregnancy loss between 22 0/7 and 27 6/7 weeks gestation 27 6/7 weeks gestation
Secondary Outcome Late fetal death defined as pregnancy loss greater than or equal to 28 0/7 weeks gestation Delivery
Secondary Outcome Pregnancy loss defined as spontaneous abortion or stillbirth End of pregnancy
Secondary Outcome Neonatal death, defined as a livebirth with death before the 28th day of life 28d after livebirth
Secondary Outcome Perinatal death, defined as late fetal death or neonatal death 28d after delivery
Secondary Outcome Clinical malaria during pregnancy Each ANC and delivery
Secondary Outcome Maternal peripheral parasitemia Delivery
Secondary Outcome Maternal hemoglobin concentration Delivery
Secondary Outcome Anemia, defined as hemoglobin concentration less than or equal to 11 g/dL Delivery
Secondary Outcome Severe anemia, defined as hemoglobin concentration less that or equal to 7 g/dL Delivery
Secondary Outcome Maternal SAEs Enrollment to 28d after delivery
Secondary Outcome Congenital malformations Until 28d after birth
Secondary Outcome Hospitalization or acute medical evaluation of the offspring Until 28d after birth
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Webuye Subcounty Hospital N/a Webuye Kenya
Bita Health Centre N/a Bita Democratic Republic of the Congo
Kingakati Health Centre N/a Kingakati Democratic Republic of the Congo
FUNDING SOURCES
Name of source Street address City Postal code Country
US National Institutes of Health N/a Bethesda MD United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Duke Clinical Research Institute 300 W Morgan St Durham NC 27701 United States of America University
COLLABORATORS
Name Street address City Postal code Country
Dr Jeremiah Laktabai PO Box 4606 30100 Eldoret Kenya
Prof Antoinette Tshefu Ex Mama Yemo Bureau UNC Pavilion 27 Kinshasa Democratic Republic of the Congo
Dr Melissa Bauserman 101 Manning Dr Chapel Hill NC United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Steve Taylor steve.taylor@duke.edu +019196848111 PO Box 102659 DUMC
City Postal code Country Position/Affiliation
Durham NC United States of America Duke University School of Medicine
Role Name Email Phone Street address
Public Enquiries Steve Taylor steve.taylor@duke.edu 000000000 n/a
City Postal code Country Position/Affiliation
na United States of America Duke University School of Medicine
Role Name Email Phone Street address
Scientific Enquiries Steve Taylor steve.taylor@duke.edu 000000000 n/a
City Postal code Country Position/Affiliation
na United States of America Duke University School of Medicine
Role Name Email Phone Street address
Principal Investigator Jeremiah Laktabai jklaktabai@gmail.com 0000000000 Moi University
City Postal code Country Position/Affiliation
Eldoret Kenya Kenya PI
Role Name Email Phone Street address
Principal Investigator Antoinette Tshefu antotshe@yahoo.com 000000000 Kinshasa School of Public Health
City Postal code Country Position/Affiliation
Kinshasa Democratic Republic of the Congo DR Congo PI
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes IPD will be available upon request to investigators following publication of results, or within 12 months of trial completion, whichever occurs earlier. At that time the Study Protocol and the Statistical Analysis Plan will also be made available. Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol At time of study completion Concordance with restrictions present in the ICF
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information