The clinical benefits and cost-effectiveness and safety of haematopoietic interventions for patients with anaemia following major emergency surgery: a phase IV, multicentre, multi-arm randomised controlled trial: Peri-op Iron and Erythropoietin (EPO) Intervention Study - POP-I

RESEARCH QUESTION

In patients 60-years or older recovering from major emergency surgery (P), is treating postoperative anaemia with IV iron (I1), or IV iron + erythropoiesis-stimulating agents (ESAs) (I2), more clinically and cost-effective compared to usual care (C), from the patients’ perspective (O)? BACKGROUND

Postoperative anaemia is associated with increased mortality, longer length of hospital stay and poorer quality of life (QOL). Current evidence and guidance is in favour of restrictive use of blood transfusion. Iron and ESAs are increasingly used in this context but there is no high-grade evidence to support their use.

AIMS AND OBJECTIVES

Aim: to improve outcomes for people who are anaemic following emergency surgery, and to determine the cost-effectiveness of drug treatments for anaemia compared with usual care. Objectives: 1. To assess the clinical effectiveness of postoperative IV iron and IV iron + ESA versus usual care respectively, for the treatment of anaemia across two major patient groups requiring emergency surgery; 2.

To monitor safety of the interventions; 3. To conduct an internal pilot to evaluate recruitment, uptake and retention rates, sample size parameter estimates, clinician protocol adherence, safety, acceptability and adherence, completeness and quality of data collection; 4. To assess the cost effectiveness/cost utility of postoperative intravenous iron and intravenous iron + ESA versus usual care respectively, and impact on resource use and QOL from a healthcare, social care and broader societal viewpoint.

METHODS

Multicentre multi-arm open-label pragmatic randomised controlled trial with integral internal pilot and concurrent economic evaluation. Setting: UK secondary care hospitals providing care for emergency laparotomy and hip fracture patients. Population: Patients >60-years, 2-10 days following emergency laparotomy or hip fracture surgery with confirmed anaemia (haemoglobin 80–110g/l).

Interventions [1: usual care, 2: iron injection (iron isomaltoside (20 mg/kg)), 3: iron (dose) + darbepoetin (1.5 mcg/kg) injection] assigned (ratio 1:1:1) using a probabilistic minimisation algorithm balancing on important prognostic factors (centre, type of surgery, age, sex, and postoperative haemoglobin concentration). Outcomes: Primary – Days at home within 30 days after surgery (DAH30); Secondary: quality of life (EQ-5D-5L), safety and costs/savings.

Sample size: 792 patients/group to achieve 90% power (2-sided 2.5% alpha adjusted for 2 principal comparisons, maximum 5% attrition) to detect a difference of 2 days in DAH30 (SD 11) between an active treatment versus usual care. Target 2,400 patients overall (rounded up). Primary analysis: generalised linear mixed effects regression modelling to compare DAH30 between groups (each active treatment group versus usual care respectively), adjusting for minimisation factors, including random effects to adjust for clustering within surgery type and centres.

We will present the mean difference, plus 95% confidence intervals for each principal comparison on an intention-to-treat basis. TIMELINE 4-years IMPACT AND DISSEMINATION

The results will be presented at scientific meetings and published in leading peer-reviewed medical journals. We will work with our patient partners, guideline writers and Royal Colleges to ensure rapid dissemination amongst healthcare professionals and changes to national treatment guidelines.