Protocol for a multicentre, parallel-group, open-label randomised controlled trial comparing ferric carboxymaltose with the standard of care in anaemic Malawian pregnant women: the REVAMP trial

Abstract

IntroductionAnaemia in pregnancy remains a critical global health problem, affecting 46% of pregnant women in Africa and 49% in Asia. Oral iron therapy requires extended adherence to achieve correction of anaemia and replenishment of iron stores. Ferric carboxymaltose (FCM) is a recently established intravenous iron formulation associated with substantial advantages in safety, speed of delivery and total dose deliverable in a single infusion. We aim to determine whether FCM given once during the second trimester of pregnancy compared with standard oral iron distributed through routine antenatal services is effective and safe for treatment of moderate to severe maternal anaemia in sub-Saharan Africa.Methods and analysisThe randomized controlled trial of the effect of intravenous iron on anaemia in Malawian pregnant women (REVAMP) is a two-arm confirmatory individually randomised trial set in Blantyre and Zomba districts in Malawi. The trial will randomise 862 women in the second trimester of pregnancy with a capillary haemoglobin concentration below 100.0 g/L. The study comprises two arms: (a) intravenous FCM (20 mg/kg up to 1000 mg) given once at randomisation, and (b) standard of care oral iron (65 mg elemental iron two times per day) for 90 days (or the duration of pregnancy, whichever is shorter) provided according to local healthcare practices. Both arms receive sulfadoxine-pyrimethamine as intermittent preventive treatment in pregnancy. The primary outcome is the prevalence of anaemia (Hb <110.0 g/L) at 36 weeks’ gestation. Secondary outcomes include birth weight, gestation duration and safety outcomes, including clinical malaria, serious perinatal events and postpartum haematologic and health-related outcomes in the mother and child.Ethics and disseminationEthical approval was granted by the Research Ethics Committee (COMREC P.02/18/2357) in Malawi and the Human Research Ethics Committee (WEHI: 18/02), Melbourne, Australia. The protocol is registered with the Australian and New Zealand Clinical Trials Registry. The results will be shared with the local community that enabled the research, and also to the international fora.Trial registration numberACTRN12618001268235; Pre-results.

A Randomized controlled trial of the Effect of intraVenous iron on Anaemia in Malawian Pregnant women (REVAMP): Statistical analysis plan

“…This statistical analysis plan is an extension of the REVAMP protocol 13 and documents version 1 dated October 26, 2021. Any changes to this version between publishing and unblinding will be tracked and still considered as planned analyses.…”

“…This paper describes the planned analysis for the REVAMP trial. This statistical analysis plan supersedes the plan provided in the trial registry and published protocol 13 . Finalization of the statistical analysis plan before study unblinding has been undertaken to ensure transparency in the methods used to analyze and report the data and ultimately create the evidence for the effects of intravenous iron supplementation on recovery from prenatal anaemia, haemoglobin, iron status, postpartum haemorrhage, and delivery outcomes.…”

“…The Randomized controlled trial of the Effect of intraVenous iron on Anaemia in Malawian Pregnant women (REVAMP) is an open-label randomized controlled trial conducted in the Blantyre and Zomba districts of Malawi designed to determine the efficacy and safety of delivering FCM (compared with standard-of-care oral iron) in women with moderate or severe anaemia in the second trimester of pregnancy 13 ( ACTRN12618001268235 ). The primary outcome of the trial is maternal anaemia at 36 weeks’ gestation, and the key neonate outcome is birthweight.…”

Prevalence of early postpartum depression and associated risk factors among selected women in southern Malawi: a nested observational study

“…We conducted a cross-sectional study nested in two ongoing studies 1) the Randomised controlled trial of Effect of intraVenous iron on Anaemia in Malawian Pregnant women (REVAMP study) [25], and 2) an observational cohort (REVAMP Observe). Based on previous estimates of the prevalence of depression (13.9% and 11.0%) among postpartum women attending child health services at health facilities in southern Malawi [20,22], we assumed the prevalence of PPD to be 13%.…”

A Randomized controlled trial of the Effect of intraVenous iron on Anaemia in Malawian Pregnant women (REVAMP): Statistical analysis plan

“…The Randomized controlled trial of the Effect of intraVenous iron on Anaemia in Malawian Pregnant women (REVAMP) is an open-label randomized controlled trial conducted in the Blantyre and Zomba districts of Malawi designed to determine the efficacy and safety of delivering FCM (compared with standard-of-care oral iron) in women with moderate or severe anaemia in the second trimester of pregnancy 13 (ACTRN12618001268235). The primary outcome of the trial is maternal anaemia at 36 weeks' gestation, and the key neonate outcome is birth weight.…”