Title: The impact of REstrictive versUs Liberal Transfusion strategy on cardiac Injury in patients undergoing surgery for Hip Fracture (RESULT-HIP).
Funder: Chief Scientist Office, Scotland

Abstract: IMPORTANCE OF PROBLEM_x000D_ Hip fracture is the most common serious injury in older people. It is the most common reason for older people to need emergency anaesthesia and surgery, and most common cause of death after an accident. More than 95% of these patients go on to have surgery. This surgery is often high-risk as patients with hip fracture may already be frail and have other health problems including heart disease and anaemia (low haemoglobin or "blood count”) either from chronic illness, bleeding at the time of injury or during surgery. These patients may be in hospital for a long time and need rehabilitation. Many of them will develop complications, including heart attacks and some will die. Doctors looking after these patients commonly prescribe a blood transfusion around the time of surgery. Research suggests that 30-40% of these patients have a blood transfusion around the time of operation. These patients often already have anaemia before surgery and lose more blood during their operations._x000D_ POTENTIAL BENEFITS_x000D_ A benefit of blood transfusion is that it may increase the amount of oxygen the blood can carry. One reason doctors prescribe blood around the time of surgery is to prevent heart attacks, which can occur if the heart doesn't receive enough oxygen. Another possible benefit of blood transfusion is that it may help patients get out of bed more quickly and recover after surgery. This is an important aspect of their recovery. However, blood transfusions can have side effects such as heart failure or increased infections after surgery, and these can delay patient recovery too. Giving unnecessary blood transfusion might be harmful and expensive. Finally, transfused blood is a scare resource that needs to used carefully._x000D_ Although some research has been done in this area, doctors are still unsure of when to prescribe blood transfusions to these patients. In particular, we are not sure about how low the blood count can safely be before a blood transfusion is ordered. Current guidelines recommend prescribing at a lower blood count, but there is research which suggests that this level is too low in patients undergoing surgery for a fractured hip, particularly if the patient has a history of heart disease. In these patients, transfusion at a higher blood count level may be better to prevent heart attacks and similar complications._x000D_ PLANNED RESEARCH_x000D_ We plan to undertake a study comparing blood transfusion at two different levels of anaemia to see which is best for patients. All patients with a broken hip and who have undergone surgery will be able to take part in this study. If they become anaemic during their treatment, they will be allocated to be transfused at one of two different blood count levels: a lower or “restrictive level” in line with current guidelines, or a higher “liberal” level. We will then measure how often post-operative heart attacks and other complications occur, length of stay in hospital, death rate and quality of life. The results of this study will help doctors looking after people decide when to give blood transfusions after hip fracture._x000D_ TEAM FOR DELIVERY_x000D_ The proposed trial has been developed by an experienced multi-professional team with patient involvement throughout. Patient groups have been involved in the design of this study and in reviewing the information we plan to give to patients. We will involve the Perioperative Medicine Clinical Trials Network, a group set up to deliver this type of research.

Lay abstract: Design: Multi-centre, participant-blind, parallel-group randomised controlled clinical and cost effectiveness trial with internal pilot. _x000D_ Setting: 30 NHS hospitals _x000D_ Population: Adults aged 60 years or older with hip fracture who become anaemic (Hb less than 90 g.L-1) during the seven days following surgery will be eligible for enrolment. Patients receiving palliative care, who have life threatening haemorrhage at the time of screening, pre-randomisation acute coronary syndrome or objection to receiving RBC transfusion will be excluded._x000D_ Health technologies being assessed: “Liberal” transfusion threshold of Hb 90 g.L-1 (target Hb 90-110 g.L-1) for duration of acute hospital stay. This is more liberal than current guidance but consistent with practice of many clinicians in this population._x000D_ Control group treatment: “Restrictive” transfusion threshold of 75 g.L-1 (target of 75-90 g.L-1) for duration of acute hospital stay. This is consistent with current NICE guidance. Many clinicians and published reviews note uncertainty and low quality of evidence for this population._x000D_ Costs and Outcomes: _x000D_ The primary outcome will be death or major adverse cardiac events (MACE) within 30 days of surgery. MACE will be defined as any combination of the following: death, myocardial Infarction, new arrhythmia, cardiac or respiratory arrest, cardiogenic pulmonary oedema. An ordinal ranking approach will be used in analysis. To maximize validity and consistency, all patients will have troponin measured at randomisation, day 1 and 5 post-randomisation and 12-lead ECGs will be performed at baseline and day 5. Primary outcome will be determined by an expert adjudication team blinded from group allocation._x000D_ The secondary outcomes at 30 days will be: all-cause mortality, myocardial injury after non-cardiac surgery, individual MACE components; other complications (acute kidney injury (AKI), infection, delirium); proportion of patients transfused; volume of blood transfused; discharge destination; hospital length of stay; and, healthcare related quality of life (HRQoL) using EQ-5D-5L._x000D_ The secondary outcomes at 120 days will be: secondary care costs up to 120 days; HRQoL (EQ-5D and SF-12), unplanned hospital readmissions within 120 days, mobility, residential status._x000D_ Health Economic evaluation: We will undertake a within-trial cost-consequence analysis and a long run post-surgery care costs analysis._x000D_ Process evaluation: We will undertake a process evaluation in the study pilot phase to examine barriers to recruitment and protocol compliance._x000D_ Follow up: 120 days post randomisation._x000D_ Sample size: 982 patients per group, giving a total sample size 1,964 participants (allowing 10% dropout rate). Based on pilot data and expert opinion we expect incidence rate for the primary outcome of 15% at 30 days and an absolute risk reduction (ARR) of 5% in the primary outcome to be a realistic meaningful effect size that would change practice (33% Relative RR; Number Needed to Treat, 20). _x000D_ Project time frames: The total project duration is 48 months. In month 1-12 we will undertake approvals, set-up and 10-site internal pilot. In months 13-24 we will set-up the remaining 20 sites. Month 25-36: will be the main recruitment phase. In months 37-48 we will complete follow-up, analysis, report writing._x000D_ Expertise: The proposed trial has been developed by an experienced multi-professional team with patient involvement throughout.

Research activity codes: 6.4 SURGERY
Health categories: BLOOD;MUSCULOSKELETAL