Prevention of Iron Deficiency Anemia Post-delivery

Study Overview
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Brief Summary
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PRIORITY is designed as a 2-arm, randomized-controlled trial focused on postpartum women. The trial will recruit women who are diagnosed with moderate anemia based on a blood sample taken 6-48 hours after childbirth. A total of 4,800 eligible women, or 600 women per research site, will be consented and enrolled in the trial. The study hypothesizes that at 6 weeks post-delivery, prevalence of the non-anemic state in women in that received a single-dose IV iron infusion between 6 and 48 hours after delivery and prior to discharge from the facility will be greater than that of women given a supply of oral iron tablets taken twice daily for 6 weeks.

Detailed Description
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PRIORITY is a 2-arm, randomized-controlled trial (RCT) that will be implemented at 8 sites in 7 countries: Bangladesh, Democratic Republic of the Congo, Guatemala, India (Nagpur and Belagavi), Kenya, Pakistan, and Zambia. The research team for each site will enroll approximately 600 women who deliver at a hospital or other facility such as a health center with delivery services. Participants will be randomized to receive a single-dose IV iron infusion between 6 and 48 hours after delivery prior to discharge from the facility or oral iron tablets taken twice daily for 6 weeks. They will then be assessed by research staff at an appropriate health facility at 6 weeks and 6 months post-delivery by providing a maternal blood sample that will be analyzed to determine Hb concentration. At each study visit, trained staff will also measure serum ferritin, serum transferrin receptor, C-reactive protein (CRP) and alpha 1 acid glycoprotein (AGP). Additionally, in the African research sites, a rapid diagnostic test (RDT) for malaria will be administered upon admission to the birthing facility, and at 6 weeks and 6 months postpartum. The Edinburgh Postnatal Depression Scale (EPDS), The World Health Organization Quality-of-Life (QOL) scale, The Maternal Fatigue Severity Scale (FSS-5R), and The Mother-to-infant Bonding Scale (MIBS) will also be used at the 6 weeks and 6 months postpartum follow up appointments to collect data for secondary study aims.The study hypothesizes that at 6 weeks post-delivery, the prevalence of the non-anemic state in women in that received a single-dose IV iron infusion between 6 and 48 hours after delivery and prior to discharge from the facility will be greater than that of women given a supply of oral iron tablets taken twice daily for 6 weeks. Secondary study aims will look at the effects of postpartum depression on maternal quality of life, fatigue, and breastfeeding initiation and retention rates. Depression is also a risk factor for reducing infant-mother bonding. The PRIORITY RCT will include an implementation research (IR) sub-study to complement the findings of the RCT trial and provide evidence about facilitators, barriers, and costs of implementation to inform global guidelines on the use of IV iron in postpartum women in Low-Middle Income Countries (LMIC). This Implementation Research (IR) sub-study will build upon the PRIORITY trial as well as other research projects to assess IV iron that are being conducted by the Jawaharlal Nehru Medical College research team in Belagavi, India, Thomas Jefferson University (TJU) and by the Aga Khan University team in Pakistan. The IR will utilize a mixed methods approach, employing both quantitative and qualitative data collection to better understand the potential barriers and facilitators to IV iron use in India and Pakistan. The implementation research will be harmonized with the timeline of the main PRIORITY trial, enabling the investigators to collect the IR data in parallel with the trial. The mixed methods IR study for the PRIORITY trial in India and Pakistan will be guided by the Consolidated Framework for Implementation Research (CFIR) and by Proctor's implementation outcomes framework. CFIR and Proctor's framework are complementary and provide a structure for guiding the types of questions and target groups for the implementation research data collection during the trial.

Official Title
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Prevention of Iron Deficiency Anemia Post-delivery (PRIORITY Trial): A Randomized Controlled Trial of the Global Network for Women's and Children's Health Research

Conditions
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Postpartum Anemia

Intervention / Treatment
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* Drug: IV iron infusion
* Drug: Oral iron tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Established pregnancy >20 weeks gestation by LMP and/or clinical assessment and/ Or USG Age: 15 years (or lower limit age eligible*) to 49 years Confirmed moderate anemia (Hb 7.0 to 9.9 g/dL, 6-48 hour after delivery based on a venous blood sample on Hemocue®) Deliver in participating study hospital or health facility Able to provide informed consent Plans to remain in study area for duration of the study Exclusion Criteria: IV Iron infusion received in past 3 weeks Contraindication to iron supplementation (some examples may include hemolytic anemia, allergy, severe infection) Blood transfusion already received or scheduled during the current hospital admission Known diagnosis of pre-existing depression or other psychiatric illness Stillbirth, major congenital anomaly, or neonatal loss prior to randomization Women testing positive and previously untreated for malaria Presenting with symptomatic anemia with dyspnea or fatigue and need for immediate correction Women with known hemoglobinopathy (sickle cell disease or thalassemia) Presence of severe allergic conditions such as severe asthma or known drug allergies Women presenting with any illness/condition requiring immediate medical care per physician's assessment

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Study participation will be individually randomized and allocated 1:1 to one of two arms stratified by site. A computer algorithm generated by the data coordinating center (DCC) will create the random assignment to one of the treatment arms based on randomly permuted block design with randomly varied block sizes. Randomization will be stratified based on delivery mode (Cesarean section vs. vaginal birth) and site. The block sizes will be known only by the Data Coordinating Center's personnel.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IV iron arm<br>Which will result in receipt of a single-dose IV iron infusion between 6 and 48 hours after delivery and prior to discharge from the facility; folate tablets per local guidelines. | Drug: IV iron infusion<br>* single-dose IV iron infusion<br>|
| Active Comparator: Oral iron comparator arm<br>Oral iron tablets (containing 60 mg of elemental iron (± folate as per local guidelines)) to be taken at a treatment dose of twice daily for 6 weeks. | Drug: Oral iron tablets<br>* 60 mg of elemental iron<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of women with non-anemic hemaglobin levels (Hb >11 g/dL) | Hemoglobin measure | 6 weeks post-delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of maternal deaths | Maternal death from any cause | From delivery to 6 months post-delivery | 
| Number of women who receive a blood transfusion post-discharge | Blood transfusion given to mother enrolled in study after randomization | through 6 months post-delivery | 
| Number of women who experience a postpartum hemorrhage requiring transfusion or major surgery | Postpartum hemorrhaging defined as those requiring transfusion of surgery | from intervention through 6 weeks post-delivery | 
| Number of women with hospitalization | Hospital admission for any reason after randomization until 6 months postpartum | through 6 months post-delivery | 
| Number of women with documentation of postpartum complications | Maternal postpartum clinical complications | Randomization through 6 weeks post delivery | 
| Number of women screening positive for postpartum depression | Edinburgh Postnatal Depression Scale (EPDS) will be used as post-partum depression screening tool | 6 weeks and 6 months | 
| Number of women with severe fatigue | Fatigue severity score (utilizing 9 question survey with a scale from 1-7 for each item; the lower the total score is the better the outcome) | 6 weeks and 6 months | 
| Differences between treatment groups in infant-mother bonding scale scores | Will utilize mother-infant (MIBS) tool | 6 weeks | 
| Differences in quality of life assessment scores | Will utilize WHO Quality of Life (QOL) - BREF tool. The minimum is 0 (bad QOL) and maximum is 100 (good QOL). | 6 weeks and 6 months | 
| Prevalence of severe/moderate/mild anemia among women | Use Hemocue hemoglobin measure to categorize anemia | 6 weeks and 6 months | 
| Maternal - Change resulting in severe/moderate/mild anemia by treatment arm | Evaluate individual changes in maternal anemia levels from randomization to 6 months | 6 months | 
| Maternal - Hemoglobin concentration by mode of delivery | Evaluate hemoglobin stratified by Cesarean delivery vs. Vaginal delivery | 6 months | 
| Maternal - Differences in ferritin and inflammatory markers by treatment group | Using centralized testing, evaluate differences by treatment group | 6 weeks, 6 months | 
| Number of neonatal infant deaths | Neonatal or infant death from any cause post-randomization | birth to 6 months | 
| Number of infants with hospitalization | Neonatal or infant hospitalization for any reason | birth to 6 months | 
| Number of women exclusive breastfeeding rate and intend to continue breastfeeding through 12 months post-delivery | Self report of breastfeeding | 6 weeks and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postpartum anemia, Anemia, Postpartum, IV Iron, Iron Tablets, Iron, Pregnancy, Maternal, Infant, Hemaglobin