Title: WHiTE 9: World Hip Trauma Evaluation 9 - Blood Cell Salvage Trial. A multi centre randomised controlled trial comparing intra operative cell salvage with standard care in the treatment of hip fractures.
Funder: Department of Health and Social Care

Abstract: Research question To determine the clinical and cost effectiveness of intraoperative cell salvage, compared to standard care, in improving health related quality-of-life in patients undergoing hip fracture surgery. Background Patients who sustain a hip fracture are typically elderly, frail, anaemic, and require urgent surgery to treat their fracture. Mortality is high; 7% and 30% at 30 days and one year respectively. Hip fracture and the urgent operative treatment is associated with acute blood loss, compounding patients pre-existing co-morbidities including anaemia. Consequently approximately 30% of patients require a donor blood transfusion. Donor blood transfusions are associated with increased rates of infections (e.g. pneumonia or wound infection), allergic reactions and longer lengths of stay. Cell salvage and autotransfusion is a technique that recovers, washes and transfuses blood lost during surgery, back to the patient. It has been shown to be an effective method of reducing donor blood transfusion in planned hip and knee replacements. Objectives The primary objective is to quantify and draw inferences on observed differences in participants health-related quality of life between the trial treatment groups at 4 months post-surgery Methods We have successfully conducted a randomised feasibility study that has demonstrated: clinician and patient equipoise through excellent recruitment. excellent followup rates of the primary outcome (89%). Based upon these feasibility data we will now conduct a multicentre RCT comparing cell salvage and autotransfusion with standard care, using a similar trial protocol within the existing multicentre cohort (WHITE). The trial will be conducted in at least 20 UK hospitals that provide hip fracture care. Patients over 60 years of age, both those with and without cognitive impairment, who sustain a hip fracture and are treated operatively, will be randomised to receive cell salvage and autotransfusion or standard care. The primary outcome will be health-related quality-of-life (HRQoL), measured using the EuroQol 5-dimension score, at 120 days post intervention. Secondary outcomes include HRQoL at 12 months, allogenic blood use, delirium, mortality, residential status, mobility, resource use and adverse events. Assuming 5% significance, 90% power and 40% attrition we will need to recruit a sample of 1128 participants at a rate of 4 per centre per month. A within-trial cost effectiveness analysis will also be conducted from a NHS & Social Care as well as societal perspective. This study has involved patients and the public in the application and trial design; they will continue to participate in trial management, oversight and dissemination planning. Timelines for delivery We will deliver this definitive trial over a further 30 months. Months 0-6: Main phase recruitment centre enrolment. Months 0-12: Patient recruitment. Months 13-25:Patients will be followed-up at 4 and 12 months post-randomisation. One additional month has been allowed for the collection of final data. Month 26: Data cleaning and query resolving. Months 27-28: Statistical analysis of the trial data. Months 29-30: Reporting Anticipated Impact and Dissemination Results will be disseminated to clinicians and patients. This definitive RCT will inform NICE guidelines on hip fracture care and blood transfusion.

Lay abstract: Every year around 70,000 people in the UK break their hip. Hip fractures are a common and very serious injury in older patients, similar in impact to a major stroke. The broken bone and the subsequent surgery mean patients inevitably lose considerable amounts of blood (about a pint on average), which can worsen their health and recovery. Blood transfusions can cause allergic reactions and increase the chance of patients developing an infection, risks that frailer patients can ill afford. We will test the benefit of collecting patients' own blood lost during surgery and transfusing it back to them - a method called cell salvage. This method is well known and used widely for other operations in the NHS, but until now has not been used for patient with a broken hip. We have proven in a preliminary study that a definitive study to answer this question is feasible. We will examine whether using cell salvage duration the operation to repair a broken hip gives a better result for people 60 years and over in at least 20 NHS hospitals across the UK. We want to look at how well people feel and how active they are a year after their fracture. Over a third of people with a broken hip have memory problems, and as they can struggle to recover from this injury we plan to include them in this study. We will also work out the cost of the two treatments &ndash; for the individual, for the health service and in terms of social support in the following year. To compare the two treatments properly we think we will need 1128 people to take part. If people agree to take part, they will be randomly put into one of two groups by a computer program to make sure that the groups are similar and the comparison is fair. After their operation all the patients will have the usual ward care, rehabilitation and follow up that is standard practice at their hospital. We will ask patients about their health, pain, walking ability and other daily activities, as well as any complications and specific costs. Their answers will be collected at the outset, 4 months and 1 year after the injury, and the results from the two groups compared. This project was developed by a team of patient representatives, clinical experts in trauma orthopaedics, study management specialists, experienced statisticians and health economists. The Oxford Clinical Trials Research Unit, based at the University of Oxford, will assure the quality of the study. A monitoring committee of patient representatives and independent experts will oversee the progress and conduct of the study.

Research activity codes: 6.4 SURGERY
Health categories: INJURIES AND ACCIDENTS