INtravenous iron and eryThropoietin to treat Anaemia following CriTical care 2: a multi-centre, randomised, parallel-group, double-blind, placebo-controlled, clinical efficacy trial (INTACT2)
Anaemic survivors of critical illness defined as patients who have received Intensive Care Society Level 2 or 3 care who are ready for discharge from Critical Care (i.e. an ICU or HDU in the UK) who are have mild or moderate anaemia (plasma haemoglobin ≤100 g/L prior to ICU/HDU discharge)
Participants will be randomised using an online database to the intervention intravenous ferric carboxymaltose 1000 mg and subcutaneous darbepoetin alfa 150 mcg) or the comparator (equal volume of 0.9% sodium chloride solution). The duration of the treatment phase will be 30-60 minutes, including a period of clinical observation. Participants will be followed up via questionnaire at 7 days/hospital discharge (whichever comes first), 30 days (questionnaire and blood samples) and 90 days via questionnaire post-randomisation. These time points cover the period of greatest morbidity, resource use, and steepest recovery trajectory for physical function in ICU survivors and provide the optimal window to detect relevant treatment effects. For the primary outcome at 90 days, participants will be offered several options to complete a follow-up questionnaire: online, telephone, postal and in person. When feasible we will obtain follow-up data at post-ICU follow-up services to reduce patient burden and increase completeness.
1. Adults (≥16 years) who required ≥24 hours critical care (defined as requiring level 3 or level 2* care at ICU admission) and are considered fit for ICU or HDU discharge by caring consultant/clinician. 2. Most recently available laboratory Hb ≤100 g/L prior to ICU/HDU discharge. 3. Provision of informed consent. *Levels of Adult Critical Care, Consensus Statement, Intensive Care Society https://ics.ac.uk/resource/levels-of-care.html
Current exclusion criteria as of 29/10/2025: 1. Acute uncontrolled infection – defined as ongoing bacteraemia and/or patient expected to be on non-prophylactic antibiotics for greater than 14 days from the date of eligibility assessment. 2. Cancer (known or suspected malignant disease and has not completed a course of curative treatment). 3. IV iron and/or rHuEPO in the last 30 days. 4. Severe chronic liver disease (defined by a Child-Pugh grade of C). 5. Patient is known to be pregnant. (a pregnancy test in individuals with childbearing potential will be performed prior to enrolment and patients who are pregnant will be excluded). 6. Diagnosis of haemochromatosis or secondary iron overload disorder. 7. Immunosuppression for organ transplant. 8. Primary neurological diagnosis and/or severe traumatic brain injury. 9. Admission to ICU following elective cardiac surgery. 10. Known hypersensitivity to iron and/or rHuEPO. 11. History of pure red cell aplasia following erythropoietin therapy. 12. Thromboembolism chemoprophylaxis is contraindicated. 13. Patient receiving palliative or end-of-life care. 14. Known allergy to derivative of latex. Previous exclusion criteria: 1. Acute uncontrolled infection – defined as ongoing bacteraemia and/or patient expected to be on non-prophylactic antibiotics for greater than 14 days from the date of eligibility assessment. 2. Cancer (known or suspected malignant disease and has not completed a course of curative treatment). 3. IV iron and/or rHuEPO in the last 30 days. 4. Severe chronic liver disease (defined by a Child-Pugh score of 3). 5. Patient is known to be pregnant. (a pregnancy test in individuals with childbearing potential will be performed prior to enrolment and patients who are pregnant will be excluded). 6. Diagnosis of haemochromatosis or secondary iron overload disorder. 7. Immunosuppression for organ transplant. 8. Primary neurological diagnosis and/or severe traumatic brain injury. 9. Admission to ICU following elect