Testing equivalence of two doses of intravenous iron to treat iron deficiency in pregnancy: A randomised controlled trial

Abstract

Objective: To test the equivalence of two doses of intravenous iron (ferric carboxymaltose) in pregnancy.

Design: Parallel, two-arm equivalence randomised controlled trial with an equivalence margin of 5%.

Setting: Single centre in Australia.

Population: 278 pregnant women with iron deficiency.

Methods: Participants received either 500 mg (n = 152) or 1000 mg (n = 126) of intravenous ferric carboxymaltose in the second or third trimester.

Main outcome measures: The proportion of participants requiring additional intravenous iron (500 mg) to achieve and maintain ferritin >30 microg/L (diagnostic threshold for iron deficiency) at 4 weeks post-infusion, and at 6 weeks, and 3-, 6- and 12-months postpartum. Secondary endpoints included repeat infusion rate, iron status, birth and safety outcomes.

Results: The two doses were not equivalent within a 5% margin at any time point. At 4 weeks post infusion, 26/73 (36%) participants required a repeat infusion in the 500-mg group compared with 5/67 (8%) in the 1000-mg group: difference in proportions, 0.283 (95% confidence interval [CI] 0.177-0.389). Overall, participants in the 500-mg arm received twice the repeat infusion rate (0.81 [SD = 0.824] versus 0.40 [SD = 0.69], rate ratio 2.05, 95% CI 1.45-2.91).

Conclusions: Administration of 1000 mg ferric carboxymaltose in pregnancy maintains iron stores and reduces the need for repeat infusions. A 500- mg dose requires ongoing monitoring to ensure adequate iron stores are reached and sustained.

Keywords: antenatal care; haematology: anaemia; medical disorders in pregnancy; obstetric haemorrhage; randomised controlled trials; risk management.