Prevention of Iron Deficiency Anemia Post-delivery

Postpartum Anemia Clinical Trial

— PRIORITY  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05590260
• Other study ID #: CP PRIORITY
• Status: Recruiting
• Phase: Phase 3
• Start date: May 30, 2023
• Est. completion date: December 1, 2025

Study information

• Verified date: December 2023
• Source: NICHD Global Network for Women's and Children's Health
• Contact: Elizabeth McClure, PhD
• Phone: 919 316 3773
• Email: mcclure[@]rti.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4800
• Est. completion date: December 1, 2025
• Est. primary completion date: October 1, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 15 Years to 49 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia
• Anemia, Iron-Deficiency
• Postpartum Anemia

Intervention

Drug:
• IV iron infusion
single-dose IV iron infusion
• Oral iron tablets
60 mg of elemental iron

Locations

Country	Name	City	State
Bangladesh	ICDDRB	Dhaka
Congo, The Democratic Republic of the	Kinshasa School of Public Health	Kinshasa
Guatemala	INCAP	Guatemala City
India	KLE Society's Jawaharlal Nehru Medical College	Belgaum	Karnataka
India	Lata Medical Research Foundation	Nagpur
Kenya	Moi University School of Medicine	Eldoret
Pakistan	The Aga Khan University	Karachi
Zambia	University Teaching Hospital	Lusaka

Sponsors (19)

Lead Sponsor

Collaborator

NICHD Global Network for Women's and Children's Health

Aga Khan University, Bill and Melinda Gates Foundation, Boston University, Columbia University, Indiana University, Institute of Nutrition of Central America and Panama, International Centre for Diarrhoeal Disease Research, Bangladesh, Kinshasa School of Public Health, KLE University Jawaharlal Nehru Medical College, Lata Medical Research Foundation, Nagpur, Moi University, RTI International, Thomas Jefferson University, University of Alabama at Birmingham, University of Colorado, Denver, University of North Carolina, Chapel Hill, University of Virginia, University Teaching Hospital, Lusaka, Zambia

Countries where clinical trial is conducted

Bangladesh,  Congo, The Democratic Republic of the,  Guatemala,  India,  Kenya,  Pakistan,  Zambia, 

References & Publications (27)

Ali SA, Tikmani SS, Saleem S, Patel AB, Hibberd PL, Goudar SS, Dhaded S, Derman RJ, Moore JL, McClure EM, Goldenberg RL. Hemoglobin concentrations and adverse birth outcomes in South Asian pregnant women: findings from a prospective Maternal and Neonatal Health Registry. Reprod Health. 2020 Nov 30;17(Suppl 2):154. doi: 10.1186/s12978-020-01006-6. — View Citation

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Auerbach M, Macdougall IC. Safety of intravenous iron formulations: facts and folklore. Blood Transfus. 2014 Jul;12(3):296-300. doi: 10.2450/2014.0094-14. No abstract available. — View Citation

Babu GR, Murthy GVS, Singh N, Nath A, Rathnaiah M, Saldanha N, Deepa R, Kinra S. Sociodemographic and Medical Risk Factors Associated With Antepartum Depression. Front Public Health. 2018 May 2;6:127. doi: 10.3389/fpubh.2018.00127. eCollection 2018. — View Citation

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Fellmeth G, Harrison S, Opondo C, Nair M, Kurinczuk JJ, Alderdice F. Validated screening tools to identify common mental disorders in perinatal and postpartum women in India: a systematic review and meta-analysis. BMC Psychiatry. 2021 Apr 20;21(1):200. doi: 10.1186/s12888-021-03190-6. — View Citation

Gomez-Ramirez S, Shander A, Spahn DR, Auerbach M, Liumbruno GM, Vaglio S, Munoz M. Prevention and management of acute reactions to intravenous iron in surgical patients. Blood Transfus. 2019 Mar;17(2):137-145. doi: 10.2450/2018.0156-18. Epub 2018 Oct 16. — View Citation

Jessani S, Saleem S, Hoffman MK, Goudar SS, Derman RJ, Moore JL, Garces A, Figueroa L, Krebs NF, Okitawutshu J, Tshefu A, Bose CL, Mwenechanya M, Chomba E, Carlo WA, Das PK, Patel A, Hibberd PL, Esamai F, Liechty EA, Bucher S, Nolen TL, Koso-Thomas M, Miodovnik M, McClure EM, Goldenberg RL. Association of haemoglobin levels in the first trimester and at 26-30 weeks with fetal and neonatal outcomes: a secondary analysis of the Global Network for Women's and Children's Health's ASPIRIN Trial. BJOG. 2021 Aug;128(9):1487-1496. doi: 10.1111/1471-0528.16676. Epub 2021 Apr 12. — View Citation

Khaskheli MN, Baloch S, Sheeba A, Baloch S, Khaskheli FK. Iron deficiency anaemia is still a major killer of pregnant women. Pak J Med Sci. 2016 May-Jun;32(3):630-4. doi: 10.12669/pjms.323.9557. — View Citation

Kramer MS, Dahhou M, Vallerand D, Liston R, Joseph KS. Risk factors for postpartum hemorrhage: can we explain the recent temporal increase? J Obstet Gynaecol Can. 2011 Aug;33(8):810-819. doi: 10.1016/S1701-2163(16)34984-2. — View Citation

Markova V, Norgaard A, Jorgensen KJ, Langhoff-Roos J. Treatment for women with postpartum iron deficiency anaemia. Cochrane Database Syst Rev. 2015 Aug 13;2015(8):CD010861. doi: 10.1002/14651858.CD010861.pub2. — View Citation

Matsunaga A, Ohashi Y, Sakanashi K, Kitamura T. Factor structure of the Postpartum Bonding Questionnaire: Configural invariance and measurement invariance across postpartum time periods. J Psychiatr Res. 2021 Mar;135:1-7. doi: 10.1016/j.jpsychires.2020.11.017. Epub 2020 Nov 9. — View Citation

Parks S, Hoffman MK, Goudar SS, Patel A, Saleem S, Ali SA, Goldenberg RL, Hibberd PL, Moore J, Wallace D, McClure EM, Derman RJ. Maternal anaemia and maternal, fetal, and neonatal outcomes in a prospective cohort study in India and Pakistan. BJOG. 2019 May;126(6):737-743. doi: 10.1111/1471-0528.15585. Epub 2019 Jan 24. — View Citation

Patel A, Prakash AA, Das PK, Gupta S, Pusdekar YV, Hibberd PL. Maternal anemia and underweight as determinants of pregnancy outcomes: cohort study in eastern rural Maharashtra, India. BMJ Open. 2018 Aug 8;8(8):e021623. doi: 10.1136/bmjopen-2018-021623. — View Citation

Rampton D, Folkersen J, Fishbane S, Hedenus M, Howaldt S, Locatelli F, Patni S, Szebeni J, Weiss G. Hypersensitivity reactions to intravenous iron: guidance for risk minimization and management. Haematologica. 2014 Nov;99(11):1671-6. doi: 10.3324/haematol.2014.111492. — View Citation

Rebecca Giallo, Catherine Wade & Mandy Kienhuis (2014) Fatigue in mothers of infants and young children: factor structure of the fatigue assessment scale, Fatigue: Biomedicine, Health & Behavior, 2:3, 119-131, DOI: 10.1080/21641846.2014.925326

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Shrestha SD, Pradhan R, Tran TD, Gualano RC, Fisher JR. Reliability and validity of the Edinburgh Postnatal Depression Scale (EPDS) for detecting perinatal common mental disorders (PCMDs) among women in low-and lower-middle-income countries: a systematic review. BMC Pregnancy Childbirth. 2016 Apr 4;16:72. doi: 10.1186/s12884-016-0859-2. — View Citation

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Sultan P, Bampoe S, Shah R, Guo N, Estes J, Stave C, Goodnough LT, Halpern S, Butwick AJ. Oral vs intravenous iron therapy for postpartum anemia: a systematic review and meta-analysis. Am J Obstet Gynecol. 2019 Jul;221(1):19-29.e3. doi: 10.1016/j.ajog.2018.12.016. Epub 2018 Dec 19. — View Citation

Taylor A, Atkins R, Kumar R, Adams D, Glover V. A new Mother-to-Infant Bonding Scale: links with early maternal mood. Arch Womens Ment Health. 2005 May;8(1):45-51. doi: 10.1007/s00737-005-0074-z. Epub 2005 May 4. — View Citation

Tolkien Z, Stecher L, Mander AP, Pereira DI, Powell JJ. Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis. PLoS One. 2015 Feb 20;10(2):e0117383. doi: 10.1371/journal.pone.0117383. eCollection 2015. — View Citation

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* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of women with non-anemic hemaglobin levels (Hb >11 g/dL)	Hemoglobin measure	6 weeks post-delivery
Secondary	Number of maternal deaths	Maternal death from any cause	From delivery to 6 months post-delivery
Secondary	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
Secondary	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
Secondary	Number of women with hospitalization	Hospital admission for any reason after randomization until 6 months postpartum	through 6 months post-delivery
Secondary	Number of women with documentation of postpartum complications	Maternal postpartum clinical complications	Randomization through 6 weeks post delivery
Secondary	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
Secondary	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
Secondary	Differences between treatment groups in infant-mother bonding scale scores	Will utilize mother-infant (MIBS) tool	6 weeks
Secondary	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
Secondary	Prevalence of severe/moderate/mild anemia among women	Use Hemocue hemoglobin measure to categorize anemia	6 weeks and 6 months
Secondary	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
Secondary	Maternal - Hemoglobin concentration by mode of delivery	Evaluate hemoglobin stratified by Cesarean delivery vs. Vaginal delivery	6 months
Secondary	Maternal - Differences in ferritin and inflammatory markers by treatment group	Using centralized testing, evaluate differences by treatment group	6 weeks, 6 months
Secondary	Number of neonatal infant deaths	Neonatal or infant death from any cause post-randomization	birth to 6 months
Secondary	Number of infants with hospitalization	Neonatal or infant hospitalization for any reason	birth to 6 months
Secondary	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

External Links

•   Auerbach M. Treatment of iron deficiency anemia in adults. 2020
•   Electronic Medicines Compendium (eMC). Ferinject (ferric carboxymaltose).
•   Electronic Medicines Compendium (eMC). Monofer 100mg/ml solution for injection/infusion.
•   Number of non-pregnant women (aged 15-49 years) with anaemia (thousands)
•   Sison G. The Morisky Medication Adherence Scale: An Overview. 2018
•   World Health Organization. Anemia
•   World Health Organization. Maternal health
•   World Health Organization. Number of pregnant women (aged 15-49 years) with anaemia (thousands)
•   World Health Organization. Prevalence of anaemia in non-pregnant women (aged 15-49) (%).
•   World Health Organization. Prevalence of anaemia in pregnant women (aged 15-49) (%).
•   World Health Organization. Prevalence of anaemia in women of reproductive age (aged 15-49) (%)
•   World Health Organization. The World Health Organization Quality of Life (WHOQOL). 2012.
•   World Health Organization. WHA65.6. Comprehensive implementation plan on maternal, infant and young child nutrition as passed by the World Health Assembly at the Sixty-fifth World Health Assembly meeting.2012.