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

Study Overview
=================
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.

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

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

Intervention / Treatment
-----------------
* Diagnostic Test: Malaria High-Sensitivity Rapid Diagnostic Test (HS-RDT)
* Drug: Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Random assignment to either a) usual antenatal care or b) testing for malaria with a high-sensitivity rapid diagnostic test followed by treatment with artemether-lumefantrine if tested positive
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HS-RDT screening/AL treatment<br>Pregnant women will be screened with a malaria HS-RDT and, if positive, treated with artemether-lumefantrine | Diagnostic Test: Malaria High-Sensitivity Rapid Diagnostic Test (HS-RDT)<br>* 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%<br>* Other names: Alere Malaria Ag P.f;Drug: Artemether-Lumefantrine 20 Mg-120 Mg Oral Tablet<br>* oral tablets: 6 doses of 80/480 mg over 3 days<br>* Other names: Coartem;|
| No Intervention: Usual antenatal care<br>Pregnant women will receive usual antenatal care | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Birthweight | Birthweight in grams | Delivery | 
| Number of infants with low birthweight | < 2500 grams, livebirth | Delivery | 
| Gestational age (GA) | GA at delivery in weeks/days, livebirth | Delivery | 
| Preterm | < 37 0/7 weeks, livebirth | Delivery | 
| Number of infants that are small for gestational age | Weight for gestational age < 10th percentile, livebirth | Delivery | 
| Number of adverse newborn outcomes | low birthweight OR preterm OR small for gestational age | Delivery | 
| Number of spontaneous abortions | Pregnancy loss < 22 0/7 weeks gestation | Delivery | 
| Number of stillbirths | Pregnancy loss ≥ 22 0/7 weeks gestation | Delivery | 
| Number of early fetal deaths | Pregnancy loss 22 0/7 - 27 6/7 weeks gestation | Delivery | 
| Number of late fetal deaths | Pregnancy loss ≥ 28 0/7 weeks gestation | Delivery | 
| Number of pregnancy losses | Spontaneous abortion OR stillbirth | Delivery | 
| Number of neonatal deaths | Before the 28th day of life, livebirth | Delivery to 28 days Post-delivery | 
| Number of perinatal deaths | Late fetal death OR Neonatal death | Delivery to 28 days Post-delivery | 
| 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) | 
| Number of mothers with peripheral parasitemia at delivery | Maternal peripheral parasitemia at delivery by PCR | Delivery | 
| Mean maternal hemoglobin concentration | Maternal hemoglobin (g/dL) | Enrollment and Delivery | 
| Number of mothers with anemia at delivery | Maternal Hb concentration ≤ 11 g/dL | Delivery | 
| Number of mothers with severe anemia at delivery | Maternal Hb concentration ≤ 7 g/dL | Delivery |