# Protocol and statistical analysis plan for a randomized controlled trial of the effect of intravenous iron on anemia in Malawian pregnant women in their third trimester (REVAMP – TT)

## TL;DR

This study tests if intravenous iron is better than oral iron for treating anemia in pregnant women in Malawi during their third trimester.

## Contribution

The study introduces a new approach using intravenous iron in primary health centers for late-pregnancy anemia in low-resource settings.

## Key findings

- The trial will assess the effectiveness of intravenous iron in improving anemia in pregnant women.
- It will evaluate safety and feasibility of the intervention in primary health centers.
- Results may influence maternal and child health outcomes in low-income countries.

## Abstract

Background:

Anemia affects 40% of pregnant women globally, leading to maternal mortality, premature birth, low birth weight, and poor baby development. Iron deficiency causes over 40% of anemia cases in Africa. Oral iron supplementation is insufficient for Low-and-Middle-Income-Countries (LMICs) to meet current WHO targets. We hypothesized that a single intravenous dose of Ferric Carboxymaltose (FCM) may be more effective than oral iron treatment for anemia recovery, particularly in these settings where women present late for antenatal care.

Methods:

This is a two-arm parallel open-label individual-randomized controlled trial in third trimester, in malaria Rapid Diagnostic Test-negative pregnant women with moderate or severe anemia - capillary hemoglobin <10 g/dL – who are randomized to receive either parenteral iron – with FCM – or standard-of-care oral iron for the remainder of pregnancy. This is the sister trial to the second-trimester
REVAMP trial, funded by the Bill and Melinda Gates Foundation (trial registration ACTRN12618001268235, Gates Grant number INV-010612). In REVAMP-TT, recruitment and treatment are performed within primary health centers. The trial will recruit 590 women across Zomba district, Malawi. The primary outcome is the proportion of anemic women - venous hemoglobin <11 g/dL - at 36 weeks’ gestation or delivery (whichever occurs first). Other pre-specified key secondary clinical and safety outcomes include maternal iron-status and hypophosphatemia, neonate birth weight, infant growth and infant iron and hematological parameters.

Discussion:

This study will determine whether FCM, delivered within primary health centers, is effective, safe and feasible for treating moderate to severe anemia in third-trimester pregnant Malawian women. This intervention could have long-term benefits for maternal and child health, resulting in improved survival and child development.