INtravenous iron to treat anaemia following CriTical care (INTACT): A protocol for a feasibility randomised controlled trial

Executive summary

Anaemia during intensive care unit (ICU) care is very common, affecting 60-80% of patients. Furthermore, around 80-90% of ICU survivors will be discharged from hospital with some degree of anaemia and will often receive no intervention or further investigation. Up to half of these patients will have persisting anaemia three to six months later. Persisting anaemia in ICU survivors has been demonstrated to be associated with poor health related quality of life, low physical function scores and high levels of fatigue. This is important because recent evidence suggests that a significant proportion of these patients have evidence of absolute and/or relative iron deficiency, which is largely untreated.

Improving recovery from critical illness is a recognised research priority. In non-critically ill patients, treating anaemia with intravenous iron has resulted in meaningful improvements in quality of life, but uncertainties regarding the benefits, risks, timing and optimal route of iron therapy in survivors of critical illness remain. Prior to embarking on a phase III, multicentre trial, a carefully designed and implemented feasibility trial is essential.

INtravenous Iron to Treat Anaemia following CriTical care (INTACT) is an open- label, feasibility, parallel group, randomised controlled trial (RCT). The overarching aim is to assess the feasibility of a future, multicentre RCT. Participants with moderate to severe anaemia (haemoglobin < 100 g.l⁻¹), who have required at least 24 hours of ICU care, and are now deemed medically stable for discharge from ICU by the attending physician will considered for inclusion. Included participants will undergo 1:1 randomisation to either a one-off dose of intravenous iron (1000 mg ferric carboxymaltose) or usual medical care using minimisation and stratified on anaemia severity and ICU length of stay. Participants will be followed up at 28- and 90-days post-randomisation. We anticipate enrolling 130 participants across three intensive care units over a 52-week recruitment period.

The primary outcome measures, which will be used to determine feasibility, are recruitment and randomisation rates, protocol adherence and completeness of follow-up. Secondary outcome measures include collecting clinical, laboratory, fatigue scores (MFI-20, FACIT-F), health-related quality of life (EQ-5D-5L) and safety data to inform the power calculations of a future definitive trial. A prespecified ‘traffic light’ system will be used as a guide for progression to a definitive trial. The trial is being funded as part of an NIHR Doctorial Research Fellowship, sponsored by the University of Oxford and has been prospectively registered (ISRCTN 137218080).