Intravenous iRon or placebO for aNaeMiA in iNtensive care: The Ironman Randomised Controlled Trial

Background Between 17 and 45% of patients admitted to an Intensive Care Unit (ICU) are reported to receive a red blood cell (RBC) transfusion and these transfusions comprise almost 20% of all RBC use in Australia. Although RBC transfusion may be life-saving in patients with major haemorrhage, the majority of patients transfused in the ICU receive RBCs for other indications including minor haemorrhage, anaemia and augmentation of cardiac output. Observational studies in critical illness identify RBC transfusion as an independent and dose-dependent risk factor for mortality and serious morbidity including transfusion-related lung injury, transfusion-associated circulatory overload, transfusion-related immunomodulation and infection. In addition to the associated risks, transfusion is also costly. The product cost of transfusing a single RBC unit in Western Australia (WA) is $370 and the total cost is $875 and increasing. There is evidence that current ICU clinical practice complies with the National Health and Medical Research Council (NHMRC) Guidelines on restrictive RBC transfusion thresholds. As such, there is little scope to reduce transfusion through better compliance with existing evidence. Novel interventions to reduce transfusion requirement in critically ill patients are therefore required urgently. Intravenous (IV) iron has been shown to be effective for the management of iron-restricted erythropoiesis, reducing RBC transfusion, in multiple well conducted RCTs in a number of patient groups. If IV iron reduces transfusion requirement in patients admitted to the ICU it will represent a promising candidate intervention to also reduce mortality and serious morbidity. However, its clinical and cost-effectiveness in patients who are critically ill in the ICU is uncertain. Aim The primary aim of the study is to determine if the administration of IV iron compared with placebo to patients admitted to an ICU and who are anaemic reduces RBC transfusion prior to hospital discharge. The secondary aim is to determine if a phase III RCT of IV iron is warranted with such a trial having the aim of determining whether IV iron, compared to placebo, results in improved patient-centred outcomes. Objectives To determine whether the administration of IV iron in patients who are admitted to an ICU and are anaemic will: 1. Reduce the mean number of transfused RBC units 2. Improve clinical outcomes including mortality at hospital discharge and duration of admission to hospital and ICU 3. Be cost-effective Methods The proposed study will be a blinded, parallel group, phase II randomised trial comparing IV iron with placebo in patients admitted to the ICU and who are anaemic. Participants will be eligible if they are within 48 hours of admission to the ICU, have had one or more measurements of Hb <100g/L within the preceding 24 hours, are expected to require ICU care beyond the next calendar day, and fulfil none of the exclusion criteria. Participants will be randomised in a 1:1 ratio to the intervention or placebo group. Participants randomised to the IV iron group will receive 500mg of ferric carboxymaltose. Participants who are randomised to the control group will receive an equivalent volume of IV 0.9% saline. The intervention will be blinded to study staff and clinical staff caring for the patient. The study will be conducted in 4 metropolitan ICUs in Perth WA comprising Fremantle Hospital, Joondalup Hospital, Royal Perth Hospital, and Sir Charles Gairdner Hospital. Outcomes The primary end-point is the mean number of RBC units transfused. The study will also investigate the effect of intravenous iron on mortality and major morbidity as well as the costs and cost-effectiveness of IV iron.