Randomized controlled trial of the Effect of intraVenous iron on Anaemia in Malawian Pregnant women

Anaemia in pregnancy remains a critical global health problem, affecting 46% of pregnant women in Africa and 49% in Asia. Antenatal anaemia is associated with critical risks for both mother and child. Control of maternal anaemia, an important contributor to maternal mortality, is a key WHO Nutrition target and component of the third Sustainable Development Goal. Treatment with oral iron is poorly tolerated and requires extended contact with a well-functioning health system; this is difficult to achieve and few women receive or consume full courses of iron. At high adherence, oral antenatal iron supplementation markedly increases birthweight and gestation duration, and appears safe in malaria endemic settings. A new intravenous iron formulation, ferric carboxymaltose, now available in developed countries, provides the opportunity to give high doses of iron (up to 15mg/kg or 1000mg) in a single rapid infusion. Unlike previous drugs which required prolonged or multiple infusions and carried a risk of severe reactions, ferric carboxymaltose can be given in just 15 minutes, and severe reactions are rare. Ferric carboxymaltose is increasingly used for first line treatment of iron deficiency in developed medical settings, including in pregnancy (For example, see clinical pathway from a recently published expert review). Thus, in low and middle-income countries, intravenous iron could present a novel, innovative opportunity to rapidly cure moderate and severe antenatal anaemia, thereby improving crucial maternal and neonatal outcomes. This open label randomized controlled effectiveness trial will assess whether, in Malawi, treatment of moderate and severe antenatal anaemia (Hb<10g/dL) with a single dose of intravenous ferric carboxymaltose up to 1000mg improves critical maternal (including anaemia, wellbeing) and neonatal (including birthweight, gestation duration) outcomes and is safe (infection, hypophosphataemia) compared to oral iron (delivered as ferrous sulfate via routine antenatal care mechanisms). Women will also receive intermittent preventive therapy against malaria (IPTp). The trial will be undertaken under full supervision of an ethical review committee and Data Safety Monitoring Board, whom will be able to assess the ongoing safety of participants in the trial. The trial will recruit 862 women in two centres in Malawi. Women will be recruited during the second trimester and be followed up until delivery.. These data will define a clinical rationale for developing the infrastructure and economic case for implementing this complex intervention in a LMIC setting.