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Trials
Published in: Trials 1/2022

Open Access 01-12-2022 | Mood Disorders | Study protocol

Intravenous versus oral iron for iron deficiency anaemia in pregnant Nigerian women (IVON): study protocol for a randomised hybrid effectiveness-implementation trial

Authors: Bosede B. Afolabi, Ochuwa A. Babah, Opeyemi R. Akinajo, Victoria O. Adaramoye, Titilope A. Adeyemo, Mobolanle Balogun, Aduragbemi Banke-Thomas, Rachel A. Quao, Gbenga Olorunfemi, Ajibola I. Abioye, Hadiza S. Galadanci, Nadia A. Sam-Agudu

Published in: Trials | Issue 1/2022

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Abstract

Background

Anaemia in pregnancy is highly prevalent in African countries. High-dose oral iron is the current recommended treatment for pregnancy-related iron deficiency anaemia (IDA) in Nigeria and other African countries. This oral regimen is often poorly tolerated and has several side effects. Parenteral iron preparations are now available for the treatment of IDA in pregnancy but not widely used in Africa.
The IVON trial is investigating the comparative effectiveness and safety of intravenous ferric carboxymaltose versus oral ferrous sulphate standard-of-care for pregnancy-related IDA in Nigeria. We will also measure the implementation outcomes of acceptability, feasibility, fidelity, and cost-effectiveness for intravenous ferric carboxymaltose.

Methods

This is an open-label randomised controlled trial with a hybrid type 1 effectiveness-implementation design, conducted at 10 health facilities in Kano (Northern) and Lagos (Southern) states in Nigeria. A total of 1056 pregnant women at 20–32 weeks’ gestational age with moderate or severe anaemia (Hb < 10g/dl) will be randomised 1:1 into two groups. The interventional treatment is one 1000-mg dose of intravenous ferric carboxymaltose at enrolment; the control treatment is thrice daily oral ferrous sulphate (195 mg elemental iron daily), from enrolment till 6 weeks postpartum.
Primary outcome measures are (1) the prevalence of maternal anaemia at 36 weeks and (2) infant preterm birth (<37 weeks’ gestation) and will be analysed by intention-to-treat. Maternal full blood count and iron panel will be assayed at 4 weeks post-enrolment, 36 weeks’ gestation, delivery, and 6 weeks postpartum. Implementation outcomes of acceptability, feasibility, fidelity, and cost will be assessed with structured questionnaires, key informant interviews, and focus group discussions.

Discussion

The IVON trial could provide both effectiveness and implementation evidence to guide policy for integration and uptake of intravenous iron for treating anaemia in pregnancy in Nigeria and similar resource-limited, high-burden settings. If found effective, further studies exploring different intravenous iron doses are planned.

Trial registration

ISRCTN registry ISRCTN63484804. Registered on 10 December 2020
Clinicaltrials.​govNCT04976179. Registered on 26 July 2021
The current protocol version is version 2.1 (080/080/2021).
Appendix
Available only for authorised users
Literature
1.
2.
Noronha JA, Khasawneh EA, Seshan V, Ramasubramaniam S, Raman S. Anemia in pregnancy-consequences and challenges: a review of literature. J SAFOG. 2012;4:64–70.CrossRef
3.
Balarajan Y, Ramakrishnan U, Ozaltin E, Shankar AH, Subramanian SV. Anaemia in low-income and middle-income countries. Lancet. 2011;378(9809):2123–35.PubMedCrossRef
4.
Parks S, Hoffman MK, Goudar SS, Patel A, Saleem S, Ali SA, et al. Maternal anaemia and maternal, fetal, and neonatal outcomes in a prospective cohort study in India and Pakistan. BJOG. 2019;126(6):737–43.PubMedPubMedCentralCrossRef
5.
Daru J, Zamora J, Fernández-Félix BM, Vogel J, Oladapo OT, Morisaki N, et al. Risk of maternal mortality in women with severe anaemia during pregnancy and post partum: a multilevel analysis. Lancet Glob Health. 2018;6(5):e548–e54.PubMedCrossRef
6.
Kang SY, Kim HB, Sunwoo S. Association between anemia and maternal depression: a systematic review and meta-analysis. J Psychiatr Res. 2020;122:88–96.PubMedCrossRef
7.
Dama M, Van Lieshout RJ, Mattina G, Steiner M. Iron deficiency and risk of maternal depression in pregnancy: an observational study. J Obstet Gynaecol Can. 2018;40(6):698–703.PubMedCrossRef
8.
Weze K, Abioye AI, Obiajunwa C, Omotayo M. Spatio-temporal trends in anaemia among pregnant women, adolescents and preschool children in sub-Saharan Africa. Public Health Nutr. 2021;24(12):3648–61.PubMedCrossRef
9.
10.
Olatunbosun OA, Abasiattai AM, Bassey EA, James RS, Ibanga G, Morgan A. Prevalence of anaemia among pregnant women at booking in the University of Uyo Teaching Hospital, Uyo, Nigeria. Biomed Res Int. 2014;2014:849080.PubMedPubMedCentralCrossRef
11.
Okafor IM, Okpokam DC, Antai AB, Usanga EA. Iron status of pregnant women in rural and urban communities of Cross River State, South-South Nigeria. Niger J Physiol Sci. 2017;31(2):121–5.PubMed
12.
Omote V, Ukwamedua HA, Bini N, Kashibu E, Ubandoma JR, Ranyang A. Prevalence, severity, and correlates of anaemia in pregnancy among antenatal attendees in Warri, South-Southern Nigeria: a cross-sectional and hospital-based study. Anemia. 2020;2020:1915231.PubMedPubMedCentralCrossRef
13.
Ukibe S. Prevalence of anaemia in pregnant women attending antenatal in Anambra State, Southeast Nigeria; 2013. p. 1.
14.
Ugwu N, Uneke C. Iron deficiency anemia in pregnancy in Nigeria: a systematic review. Niger J Clin Pract. 2020;23(7):889–96.PubMedCrossRef
15.
Ajepe AA, Okunade KS, Sekumade AI, Daramola ES, Beke MO, Ijasan O, et al. Prevalence and foetomaternal effects of iron deficiency anaemia among pregnant women in Lagos, Nigeria. PLoS One. 2020;15(1):e0227965.PubMedPubMedCentralCrossRef
16.
Wilson ML, Fleming KA, Kuti MA, Looi LM, Lago N, Ru K. Access to pathology and laboratory medicine services: a crucial gap. Lancet. 2018;391(10133):1927–38.PubMedCrossRef
17.
18.
Auerbach M, Gafter-Gvili A, Macdougall IC. Intravenous iron: a framework for changing the management of iron deficiency. Lancet Haematol. 2020;7(4):e342–e50.PubMedCrossRef
19.
FMOH. National clinical service protocol for obstetric and neonatal care. In: health, editor. Abuja: Federal Ministry of Health; 2006.
20.
Fite MB, Roba KT, Oljira L, Tura AK, Yadeta TA. Compliance with iron and folic acid supplementation (IFAS) and associated factors among pregnant women in sub-Saharan Africa: a systematic review and meta-analysis. PLoS One. 2021;16(4):e0249789-e.CrossRef
21.
Jimenez K, Kulnigg-Dabsch S, Gasche C. Management of iron deficiency anemia. Gastroenterol Hepatol (N Y). 2015;11(4):241–50.
22.
Bonovas S, Fiorino G, Allocca M, Lytras T, Tsantes A, Peyrin-Biroulet L, et al. Intravenous versus oral iron for the treatment of anemia in inflammatory bowel disease: a systematic review and meta-analysis of randomized controlled trials. Medicine. 2016;95(2):e2308.PubMedPubMedCentralCrossRef
23.
24.
25.
Van Wyck DB, Martens MG, Seid MH, Baker JB, Mangione A. Intravenous ferric carboxymaltose compared with oral iron in the treatment of postpartum anemia: a randomized controlled trial. Obstet Gynecol. 2007;110(2 Pt 1):267–78.PubMedCrossRef
26.
27.
Vanobberghen F, Lweno O, Kuemmerle A, Mwebi KD, Asilia P, Issa A, et al. Efficacy and safety of intravenous ferric carboxymaltose compared with oral iron for the treatment of iron deficiency anaemia in women after childbirth in Tanzania: a parallel-group, open-label, randomised controlled phase 3 trial. Lancet Glob Health. 2021;9(2):e189–e98.PubMedCrossRef
28.
Damschroder LJ, Aron DC, Keith RE, Kirsh SR, Alexander JA, Lowery JC. Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science. Implement Sci. 2009;4:50.PubMedPubMedCentralCrossRef
29.
Sam-Agudu NA, Akinajo OR, Balogun M, Babah OA, Banke-Thomas A, Quao RA, et al. Formative research and protocol adjustments for the intravenous vs oral iron for iron deficiency anemia in pregnant Nigerian women (IVON) trial. 14th annual conference on the science of dissemination and implementation in health; 2021.
30.
Curran GM, Bauer M, Mittman B, Pyne JM, Stetler C. Effectiveness-implementation hybrid designs: combining elements of clinical effectiveness and implementation research to enhance public health impact. Med Care. 2012;50(3):217–26.PubMedPubMedCentralCrossRef
31.
Chan AW, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin JA, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013;346:e7586.PubMedPubMedCentralCrossRef
32.
Yar'Zever I. Knowledge and barriers in utilization of maternal health care services in Kano state, Northern Nigeria. Eur J Biol Med Sci Res. 2013;1:1–14.
33.
Ademuyiwa I, Faronbi J, Olufemi O, Erondu CU. Antenatal care services utilization and factors influencing it among pregnant women in a teaching Hospital in Lagos, Nigeria. Trop J Health Sci. 2020;27:1–6.
34.
35.
Nwizu EN, Iliyasu Z, Ibrahim SA, Galadanci HS. Socio-demographic and maternal factors in anaemia in pregnancy at booking in Kano, northern Nigeria. Afr J Reprod Health. 2011;15(4):33–41.PubMed
36.
Erhabor O, Muhammad AD, Adias TC, Ahmed Y, Erhabor T. Anaemia and thrombocytopenia among pregnant women attending Aminu Kano teaching hospital, Kano state, North Western Nigeria. Hum Antibodies. 2020;28(1):11–9.PubMedCrossRef
37.
Olukosi AY, Olakiigbe A, Ajibaye O, Orok BA, Aina OO, Akindele SK, et al. Socio-economic behavioural indicators of falciparum malaria parasitaemia and moderate to severe anaemia among pregnant women attending antenatal clinics in Lagos, Southwest Nigeria. Malar J. 2020;19(1):393.PubMedPubMedCentralCrossRef
38.
Anorlu RI, Oluwole AA, Abudu OO. Sociodemographic factors in anaemia in pregnancy at booking in Lagos, Nigeria. J Obstet Gynaecol. 2006;26(8):773–6.PubMedCrossRef
39.
Chandrasekaran N, De Souza LR, Urquia ML, Young B, McLeod A, Windrim R, et al. Is anemia an independent risk factor for postpartum depression in women who have a cesarean section? - a prospective observational study. BMC Pregnancy Childbirth. 2018;18(1):400.PubMedPubMedCentralCrossRef
40.
Shim J-Y, Kim MY, Kim YJ, Lee Y, Lee JJ, Jun JK, et al. Efficacy and safety of ferric carboxymaltose versus ferrous sulfate for iron deficiency anemia during pregnancy: subgroup analysis of Korean women. BMC Pregnancy Childbirth. 2018;18(1):349.PubMedPubMedCentralCrossRef
41.
Bolarinwa OA. Sample size estimation for health and social science researchers: the principles and considerations for different study designs. Niger Postgrad Med J. 2020;27(2):67–75.PubMedCrossRef
42.
Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–81.PubMedCrossRef
43.
Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O'Neal L, et al. The REDCap consortium: building an international community of software platform partners. J Biomed Inform. 2019;95:103208.PubMedPubMedCentralCrossRef
44.
45.
Weiner BJ, Lewis CC, Stanick C, Powell BJ, Dorsey CN, Clary AS, et al. Psychometric assessment of three newly developed implementation outcome measures. Implement Sci. 2017;12(1):108.PubMedPubMedCentralCrossRef
46.
47.
Ray S, Neogi SB, Singh R, Devasenapathy N, Zodpey S. Is IV iron sucrose a cost-effective option for treatment of severe anaemia in pregnancy as compared with oral iron? Health Policy Plan. 2021;35(10):1339–46.PubMedCrossRef
48.
Werner EFWS, Burd I. Creating decision trees to assess cost-effectiveness in clinical research. J Biomet Biostat. 2012;S7:004.
49.
Garrison LP, Mansley EC, Abbott TA, Bresnahan BW, Hay JW, Smeeding J. Good research practices for measuring drug costs in cost-effectiveness analyses: a societal perspective: the ISPOR drug cost task force report—part II. Value Health. 2010;13(1):8–13.PubMedCrossRef
50.
51.
Govindappagari SBR. Treatment of iron deficiency anemia in pregnancy with intravenous versus oral iron: systematic review and meta-analysis. Am J Perinatol. 2019;36(04):366–76.PubMedCrossRef
52.
Lewkowitz AK, Gupta A, Simon L, Sabol BA, Stoll C, Cooke E, et al. Intravenous compared with oral iron for the treatment of iron-deficiency anemia in pregnancy: a systematic review and meta-analysis. J Perinatol. 2019;39(4):519–32.PubMedCrossRef
53.
Banke-Thomas A, Madaj B, Kumar S, Ameh C, van den Broek N. Assessing value-for-money in maternal and newborn health. BMJ glob. Health. 2017;2(2):e000310-e.
54.
55.
Breymann C, Milman N, Mezzacasa A, Bernard R, Dudenhausen J. Ferric carboxymaltose vs. oral iron in the treatment of pregnant women with iron deficiency anemia: an international, open-label, randomized controlled trial (FER-ASAP). J Perinat Med. 2017;45(4):443–53.PubMedCrossRef
56.
Jose A, Mahey R, Sharma JB, Bhatla N, Saxena R, Kalaivani M, et al. Comparison of ferric carboxymaltose and iron sucrose complex for treatment of iron deficiency anemia in pregnancy- randomised controlled trial. BMC Pregnancy Childbirth. 2019;19(1):54.PubMedPubMedCentralCrossRef
57.
Zeba D, Khanam PA, Ahamed M, Khair MA. Intravenous iron treatment in pregnancy: ferric carboxymaltose for correction of iron deficiency anaemia. Faridpur Med College J. 2017;12(2):54–7.CrossRef
58.
Khalafallah AA, Hyppa A, Chuang A, Hanna F, Wilson E, Kwok C, et al. A prospective randomised controlled trial of a single intravenous infusion of ferric carboxymaltose vs single intravenous iron polymaltose or daily oral ferrous sulphate in the treatment of iron deficiency anaemia in pregnancy. Semin Hematol. 2018;55(4):223–34.PubMedCrossRef
59.
Mishra V, Gandhi K, Roy P, Hokabaj S, Shah KN. Role of intravenous ferric carboxy-maltose in pregnant women with iron deficiency anaemia. J Nepal Health Res Counc. 2017;15(2):96–9.PubMedCrossRef
60.
Ezeanolue EE, Powell BJ, Patel D, Olutola A, Obiefune M, Dakum P, et al. Identifying and prioritizing implementation barriers, gaps, and strategies through the Nigeria implementation science Alliance: getting to zero in the prevention of mother-to-child transmission of HIV. J Acquir Immune Defic Syndr. 2016;72 Suppl 2(Suppl 2):S161–6.PubMedCrossRef
61.
Metadata
Title
Intravenous versus oral iron for iron deficiency anaemia in pregnant Nigerian women (IVON): study protocol for a randomised hybrid effectiveness-implementation trial
Authors
Bosede B. Afolabi
Ochuwa A. Babah
Opeyemi R. Akinajo
Victoria O. Adaramoye
Titilope A. Adeyemo
Mobolanle Balogun
Aduragbemi Banke-Thomas
Rachel A. Quao
Gbenga Olorunfemi
Ajibola I. Abioye
Hadiza S. Galadanci
Nadia A. Sam-Agudu
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Trials / Issue 1/2022
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-022-06690-2

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