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

Abstract

Background: Anaemia affects more than half of Africa’s pregnancies. Standard care, with oral iron tablets, often fails to achieve results, with compliance and gastrointestinal side-effects being a significant issue. In recent years, intravenous iron formulations have become safe, effective, and quick to administer, allowing the complete iron requirements of pregnancy to be provided in one 15-minute infusion. The Randomized controlled trial of the Effect of intraVenous iron on Anaemia in Malawian Pregnant women (REVAMP) will evaluate whether a modern intravenous iron formulation, ferric carboxymaltose (FCM), given once during the second trimester is effective and safe in improving maternal and neonatal outcomes for treatment of moderate to severe anaemia in sub-Saharan Africa. The objective was to publish the detailed statistical analysis plan for the REVAMP trial prior to unblinding the allocated treatments and performing the analysis. Methods: REVAMP is a multicentre, two-arm, open-label, parallel-group randomized control trial (RCT) in 862 pregnant women in their second trimester. The trial statistician developed the statistical analysis plan in consultation with the trial management team based on the protocol, data collection forms, and study outcomes available in the blinded study database. Results: The detailed statistical analysis plan will support the statistical analyses and reporting of the REVAMP trial after unblinding the treatment allocations. Conclusions: A statistical analysis plan allows for transparency as well as reproducibility of reporting and statistical analyses.

Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial

“…The protocol and statistical analysis plan are included in the appendix (pp 11–220 ) and were published before database lock. 17 , 18 The trial was approved by ethics committees at the College of Medicine, University of Malawi, Zomba, Malawi; and The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia. All authors attest to the completeness and accuracy of the data and analyses and the adherence of the trial to the protocol.…”

“…Analysis followed a pre-specified statistical analysis plan. 17 Maternal and neonatal efficacy outcomes were analysed according to the randomly allocated group of the woman and included all available data, targeting the intention-to-treat principle.…”

Ferric Carboxymaltose and Erythropoiesis-Stimulating Agent Treatment Reduces the Rate of Blood Transfusion in Refractory Anemia

“…Administered intravenously, it is effective in the treatment of iron deficiency anemia, delivering a replenishment dose of up to 1000 mg of iron during a minimum administration time of </= 15 min [ 13 , 14 , 15 , 16 , 17 ]. Results of several randomized trials have shown that intravenously administered FCM rapidly improves hemoglobin levels and replenishes depleted iron stores in various populations of patients with iron deficiency anemia, including those with inflammatory bowel disease [ 13 ], heavy uterine bleeding [ 14 ], postpartum iron deficiency anemia [ 15 ], heart failure [ 16 ], and chronic kidney disease [ 17 ]. It is also well tolerated in clinical trials [ 13 , 14 , 15 , 16 , 17 ].…”

“…Results of several randomized trials have shown that intravenously administered FCM rapidly improves hemoglobin levels and replenishes depleted iron stores in various populations of patients with iron deficiency anemia, including those with inflammatory bowel disease [ 13 ], heavy uterine bleeding [ 14 ], postpartum iron deficiency anemia [ 15 ], heart failure [ 16 ], and chronic kidney disease [ 17 ]. It is also well tolerated in clinical trials [ 13 , 14 , 15 , 16 , 17 ]. FCM is, therefore, an effective option in the treatment of iron deficiency anemia in patients for whom oral iron preparations are ineffective or cannot be administered.…”