Title: Effectiveness and cost-effectiveness of Reverse Shoulder Arthroplasty versus Hemiarthroplasty versus Non-surgical care for acute 3 and 4 part fractures of the proximal humerus in older adults - The PROFHER-2 Randomised Clinical Trial
Funder: Department of Health and Social Care

Abstract: DESIGN: Multi-centre, open-label, 3-arm parallel group, pragmatic, randomised controlled trial with internal pilot to determine if Reverse Shoulder Arthroplasty (RSA) is more clinically & cost effective than Hemiarthroplasty (HA) in treating complex fractures of the proximal humerus; & to determine if either surgery is more effective than non-surgical care (NS) SETTING: Secondary care NHS hospitals TARGET POPULATION Inclusion: Consenting patients, 65 years of age or older, with a displaced multifragmentary (more than 2 parts) fracture presenting within 3 weeks of injury Exclusion: Patients not fit for anaesthesia; pathological (other than osteoporotic) fractures; lack of mental capacity to understand the trial or instructions for rehabilitation OUTCOME MEASURES Primary outcome is difference in mean OSS between RSA & HA 2 years after surgery. Difference in OSS between surgical (RSA or HA) & non surgical treatment will also be determined. Secondary outcomes include differences in EQ-5D scores; pain & range of motion. Data on perioperative care (including details of anaesthesia), physiotherapy, complications of surgery, further procedures & adverse events will be collected. SAMPLE SIZE: To detect a 5-point difference in OSS between surgical arms & a 6-point difference between either surgical arm & NS with 90% power, a total of 380 participants are required, assuming a SD of 12, 5% 2-sided statistical significance & 15% attrition at 2 years. RANDOMISATION: Randomisation will be imbalanced with a ratio of 2:2:1, favouring recruitment to RSA & HA arms. It will be done by York Trials Unit's secure, web-based, randomisation service ensuring adequate allocation concealment. PROJECT PLAN: The study will take 72 months, recruiting over 36 months at around 35 sites. Participant follow-up will be at 6 months, 1 year and 2 years. There will be a 12-month internal pilot phase from start of recruitment, by the end of which we aim set up 50% of centres, recruiting on average one participant per centre every 2 months to confirm recruitment assumptions & progress the trial accordingly. An extension phase for remote follow-up to 5 years will be considered based on findings of the main study. This position has been strengthened by the support for this application provided by the National Joint Registry. STATISTICAL ANALYSIS: Primary analysis will assess OSS scores by longitudinal regression analysis up to 2 years follow-up for three group comparisons: RSA vs HA, RSA vs NS & HA vs NS, adjusting for relevant baseline characteristics. Surgeons will be added as a random effect to account for individual differences. Potential learning effects for surgical techniques will be explored. Secondary outcomes will be analysed by longitudinal regressions appropriate for each type of outcome variable. HEALTH ECONOMICS: Costs & EQ-5D index score will be collected to conduct a cost-utility analysis up to 2 years to identify the most efficient provision of future care within the NHS. We will estimate incremental costs & QALYs & Net Monetary Benefit by means of regression methods. Probabilistic sensitivity analysis will be conducted to test the robustness of the results. We will extrapolate long-term cost-effectiveness beyond the trial if deemed appropriate. PROJECT TEAM: We have assembled an expert multidisciplinary team of clinicians, patient representatives, methodologists, health economists, & statisticians with vast experience in running such studies

Lay abstract: Breaking (fracturing) the upper part of the arm at the shoulder (proximal humerus) most commonly occurs in people over 65 years old after a simple fall. Less serious fractures of the proximal humerus are usually successfully treated by supporting the injured arm in a sling until the fracture heals. Fractures are considered more serious & complex when the bone is broken into more than 2 parts or are widely separated. Patients with these fractures may undergo surgery to replace the broken bone with an artificial shoulder joint. There are two main types of joint replacement used: hemiarthroplasty, which involves replacing only the broken 'ball' of the joint, or reverse shoulder arthroplasty which replaces both the ball and socket, but replaces the ball with a socket and the socket with a ball (hence ‘reverse’). Use of the reverse method is increasing. Another common treatment is non-surgical care where the arm is supported in a sling to allow the broken bone to heal naturally. Following each of these treatments, good physiotherapy is needed to regain arm function. We do not know which surgery leads to the best recovery & also whether surgery is better than non-surgical care (allowing the arm to heal naturally while in a sling). The advantage of reverse shoulder arthroplasty is thought to be improved function with less physiotherapy and rehabilitation. However, it may have higher complication rates compared to hemiarthroplasty and it is a more complex and expensive operation. Non-surgical treatment has the advantage of avoiding the risks of surgery but it is uncertain whether recovery is as good as with surgery. There needs to be good quality research to assess which is the most effective treatment. Recent high-quality research (the PROFHER Trial) found that many fractures of the proximal humerus can be treated without surgery. However, it did not focus on the most severe type of fracture where the bone is broken into many parts. Surgeons therefore remain unsure about how to treat the more severe fractures. Our research (PROFHER-2) will assess whether reverse shoulder arthroplasty is more effective than hemiarthroplasty at restoring use of the shoulder & arm in patients with the most severe fractures. We will also investigate whether shoulder replacement surgery is more effective than non-surgical treatment for these fractures. Patients 65 years or older, with complex fractures of the proximal humerus, will be invited to take part in a randomised controlled trial comparing the three treatments. Patients who agree to take part will be allocated to one of the three treatments by chance using a computer system. All patients will also receive physiotherapy & rehabilitation. Questionnaires will be used to assess how well patients can use their arm and shoulder over a two-year period; and they will have the usual check-ups with their treating doctors. We also plan to follow-up patients after five years to assess whether they need any further surgery. Our patient advisor, who has had a shoulder fracture, has advised that these follow up checks & questionnaires are reasonable for someone with this injury. The study will also find out the cost of these treatments to determine which is better value for money. It will look at the impact of these treatments on hospital resources such as the time spent in hospital, in surgery & use of physiotherapy. Our core team led the successful PROFHER Trial & is experienced in this type of research.

Research activity codes: 6.4 SURGERY;6.7 PHYSICAL
Health categories: INJURIES AND ACCIDENTS