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

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 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 randomized 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 1,056 pregnant women at 20 – 32 weeks’ gestational age with moderate or severe anaemia (Hb < 10g/dl), will be randomized 1:1 into two groups. The interventional treatment is one 1000 mg dose of intravenous ferric carboxymaltose at enrolment; control treatment is thrice daily oral ferrous sulphate (195 mg elemental iron daily), from enrolment till 6 weeks postpartum.Primary outcome measures are: 1) 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 The trial has been registered at the WHO clinical trial registry (ISRCTN63484804, registration date 10/12/2020) and Clinicaltrials.gov (NCT04976179 registration date 26/07/2021). The current protocol version is Version 2.1.