The clinical benefits and cost effectiveness and safety of haematopoietic interventions for patients with anaemia following major emergency surgery: a Phase IV, multisite, multi-arm randomised controlled trial: Peri-op Iron and EPO Intervention Study (POP-I)
Postoperative anaemia
The trial objective is to assess the clinical effectiveness of postoperative intravenous iron and intravenous iron plus a subcutaneous injection of an Erythropoiesis Stimulating Agent (ESA) compared to a usual care control group respectively, for the treatment of anaemia across two major patient groups who have had emergency surgery (i.e., hip fracture and emergency laparotomy). The trial is a three-arm CTIMP that is predicated on two primary comparisons of (1) a monotherapy and (2) a combination therapy, compared with a single common control group (usual care) respectively, in a superiority hypothesis testing framework. 1. Usual Care (without additional anaemia therapy) is based upon care at sites aligned to national standards and guidelines including: NICE CG124, National Hip Fracture Database (NHFD), Association of Anaesthetists (hip fracture); National Emergency Laparotomy Audit (NELA) (emergency laparotomy); Best Practice Tariff (emergency laparotomy and hip fracture). 2. Iron Monotherapy consists of usual care (as above) plus intravenous Ferric Derisomaltose (approximately 20 mg/kg as a single dose before discharge). 3. Combination Iron and ESA consists of usual care plus intravenous Ferric Derisomaltose (as above) plus a subcutaneous injection of Darbepoetin (approximately 2 mcg/kg as a single dose before discharge). Eligible participants will be randomised via a secure password-protected 24/7 website hosted by Nottingham Clinical Trials Unit. Allocation (ratio 1:1:1) will be assigned using a probabilistic minimisation algorithm balancing across the three groups on five important factors - recruiting site, type of surgery, age, sex, and postoperative haemoglobin concentration at randomisation. Follow up takes place remotely at day 30 and day 120 post-randomisation. Follow up takes the from of a series of short questionnaires including: 1. Days at Home 2. Health related QoL (EQ-5D-5L) 3. Self-reported Mobility 4. Complications 5. Health Resource Usage
1. Age 60 years or older. 2. Hb 80–110 g/l measured on any day between day 1 and day 10 after surgery. 3. Major non-elective surgery in the last 1 to 10 days: Patient will have undergone either Emergency Laparotomy as defined by National Emergency Laparotomy Audit (NELA) OR Fragility Hip Fracture surgery as defined by National Hip Fracture Database (NHFD). • Written informed consent from participant or personal legal representative.
1. Use of intravenous iron, darbepoetin or other ESAs in last 30 days 2. Haematological diagnoses where iron overload is a risk (e.g., haemochromatosis or alpha-thalassaemia trait) or alternative treatments are indicated (e.g., haematological malignancies) 3. Acute uncontrolled infection as judged by the treating clinician (e.g. ongoing bacteraemia or non-resolving sepsis) or patient expected to be on non-prophylactic antibiotics for greater than 14 days 4. Contraindication to thromboprophylaxis 5. Direct contraindications to IMP: 5.1. Disturbances of iron, iron overload 5.2. Uncontrolled hypertension 5.3. Red cell aplasia 5.4. Decompensated/severe chronic liver disease (Child Pugh C) 5.5. Advanced cancer (metastatic and/or receiving chemo/radiotherapy) 6. Patient not expected to survive for 30 days 7. Renal replacement therapy 8. Immunosuppressive therapy for organ transplant