Title: Subacromial spacer for Tears Affecting Rotator cuff Tendons: a Randomised, Efficient, Adaptive Clinical Trial in Surgery (START:REACTS)
Funder: Department of Health and Social Care

Abstract: The introduction of safe and effective surgical techniques benefits patients. This often happens in an uncontrolled manner based on sparse evidence. Introducing procedures across the NHS that are unsafe or ineffective will harm patients and generate substantial costs. We propose a trial design that can efficiently detect if a procedure is harmful or is ineffective and allow a device or procedure to be removed from practice rapidly, but can progress to demonstrate evidence of superiority if required. We will use an adaptive design, with the purpose of achieving sufficient evidence to allow a procedure to be discarded, or to be used with confidence if it is effective. If the trial design is successful, it will set an example for the assessment of new surgical procedures internationally. Rotator cuff tears of the shoulder are common. In most instances, these are repaired but irreparable tears are difficult to treat and lead to substantial pain and disability. A potential solution is the InSpace device (OrthoSpace, Israel), a dissolvable saline filled balloon that sits above the torn tendons to improve joint function and reduce pain. It is costly and current evidence is from very small case series only. A 2016 NICE guidance restricted its use to research studies and recommended that a trial is needed.(1) START:REACTS is a participant and assessor blinded, adaptive, multi-centre randomised trial of up to 212 patients in 10 centres. People with an irreparable rotator cuff tear will be eligible. Other inclusion criteria will be intrusive symptoms (pain +/- loss of function) and failure of non-operative care. If the maximum sample size is required, recruitment will take 24 months. We will test the addition of the InSpace balloon to current usual surgical care; arthroscopic debridement of the subacromial space with retention of the coraco-acromial ligament and a biceps tenotomy (if still present). The post-operative rehabilitation package will be the same for both groups. The primary outcome will be the Constant-Murley score at 12 months, which is widely used in trials and has good reliability and responsiveness. Secondary outcomes include the Constant-Murley score at other time points, range of motion, strength, OSS and WORC scores, EQ-5D-5L, adverse events and resource use. Randomisation will be in theatre. The participant and outcome assessors will be blinded throughout. We will establish futility stopping using three, six, and 12 month follow up data starting one year after randomisation; with the final analysis adjusted for futility stopping. The decision regarding futility will be primarily based on the three-month score, supported by available six and 12 month scores. The balloon degrades after three months, meaning its maximum effect should be evident at this time. In a sub-study in 56 participants we will assess the proposed mechanism of action of the balloon. MRI scans will be performed at six-weeks and six-months post-operatively with the deltoid at rest and active to allow a comparison of acromio-humeral distance between the two treatment groups. The main analysis will be on an intention-to-treat basis using a mixed- model. A statistical work package will assess the use of Bayesian approaches to adaptive designs. An economic analysis will also be performed. Different approaches to how interim economic analyses might inform adaptive designs will be evaluated, informing adaptive trials in the future.

Lay abstract: The introduction of new surgical procedures to the NHS can bring great benefit to patients but it is important that this is done safely. Most new procedures are taken up by surgeons based on simple research which cannot determine whether a treatment is effective or is harmful. This means that a procedure may be used across the NHS for many years before its risks and benefits are known. Ineffective or unsafe treatments may be used for years before being withdrawn. Then again, effective treatments may be underused, or even restricted, because of a lack of evidence that they work. A method of studying new surgical procedures is required which can quickly determine if a procedure is ineffective or harmful. However, the study should be able to continue and provide good quality evidence when a procedure shows early promise. To do this we propose a study design that monitors the outcomes as the study progresses. If there is clear evidence that a procedure is harmful or ineffective the study can be stopped early. This will prevent ongoing harm to patients across the NHS and will reduce costs. If the study needs to run longer to accurately assess the overall benefit, it will be able to do so. NICE have identified a device called the InSpace balloon that could provide substantial benefit for patients with tears of tendons around the shoulder. Such tears are common, and they can cause substantial pain and loss of movement. Some tears cannot be repaired and can be very difficult to treat. A keyhole operation is often used to clear space around the shoulder (called an arthroscopic debridement), but frequently this fails to resolve the problem. The InSpace balloon can be added at the end of this operation and sits above the tendons, allowing the shoulder to function normally for a period of time before it dissolves, giving the other muscles a chance to strengthen and compensate. The balloon is simple to insert and adds only 10 minutes to the operation, and complications are thought to be rare. It is not known whether this expensive device helps patients, or even if it is harmful. The aim of this study is to compare arthroscopic debridement (the standard operation) to arthroscopic debridement with the InSpace balloon. We will recruit 212 people needing shoulder surgery from 10 expert centres, which will ensure that well-trained surgeons are performing the procedure correctly. Patients will be randomly allocated to one or other treatment. As the incisions and post-operative physiotherapy are the same, neither the patient nor the person assessing the results will know which treatment has been given. This will ensure a fair and unbiased comparison. Patients will be seen at three, six, and 12 months when we will measure strength, range of motion and pain. We will also use questionnaires to assess disability, quality of life, and costs, including lost earnings. A group of 56 patients will also have shoulder scans taken six-weeks and six-months after surgery, to assess the way the balloon is thought to work. This study will determine whether the device improves shoulder function, pain and quality of life following this shoulder operation. We will also assess the link between costs and the benefits that the treatment gives. This will improve care for patients suffering from a difficult condition to treat and it will also advance the way we assess new surgical procedures and run clinical trials in the future.

Research activity codes: 6.3 MEDICAL DEVICES;6.4 SURGERY
Health categories: MUSCULOSKELETAL