Title: The Meniscal Transplant surgery or Optimised Rehabilitation full randomised trial (MeTeOR2)
Funder: Department of Health and Social Care

Abstract: What is the problem?_x000D_ Inside our knees we have pieces of cartilage (menisci) that provide a cushion between the thigh bone and the shin bone. Injuries that twist the knee such as sporting injuries can damage these. Treatment of this often involves surgical removal of the torn cartilage. Around 80,000 people have this operation each year in England. This operation improves pain for many people. However, for some the pain and disability persists or gets worse over time. People with this problem describe it as having a major impact on their lives._x000D_ _x000D_ It can be hard to decide what treatment to use for people with pain and disability who have had the meniscus cartilage removed from the knee. Some surgeons try to improve pain and function by replacing the lost meniscus with a transplant from a donor who has died. This is called a meniscal allograft transplant (MAT). The alternatives for people who have problems after removal of a meniscus are non-surgical treatments like exercises, physiotherapy, and bracing._x000D_ _x000D_ Some research suggests that MAT might help people who have had a damaged meniscus removed, and the surgery could prevent future arthritis. Non-surgical treatments aim to reduce pain and improve function and can be successful. We do not know if the results for people who have MAT are better or worse than for non-surgical treatments. We do not know if these transplants are good value for money compared to the best non-surgical alternative._x000D_ _x000D_ What do we want to find out?_x000D_ We want to find out if MAT is better, the same, or worse than a package of best possible non-surgical care. This will be in the form of a Personalised Knee Therapy (PKT) programme specific to this condition._x000D_ _x000D_ How are we going to do this?_x000D_ We will recruit 144 people who have knee pain and disability after having had a damaged meniscus removed. We will recruit participants from knee clinics in the UK, Canada, Europe, and Australia. Those who agree to take part may have either a MAT or the PKT programme. We will assign people to their treatment at random. We will monitor participants and send questionnaires related to their recovery (such as level of disability, pain, mental well-being, their general health and complications) at 3, 6, 12, 18 and 24 months after joining the study. We will use questionnaires sent by post, or using a smartphone app designed specifically for the study. As well as finding out if MATs reduce pain and disability, we will also find out if they are good value to the NHS. To do this we will ask about people’s general health and find out the costs of treating their knee in different ways._x000D_ _x000D_ Patient and public involvement_x000D_ Several patient partners have contributed to the design. They all saw the study as important. They emphasised pain and function, return to work and sport, and mental health as important. They emphasised the value of a comprehensive package of non-surgical care; we have included this. We have established a patient advisory group as well as having patient partners as co-applicants. Patient partners will be involved in all aspects of the design and delivery of the trial._x000D_ _x000D_ Dissemination_x000D_ We will publish results in scientific journals and present at international and national meetings. We will prepare a summary to help NICE make a recommendation on MAT for the NHS. With the help of our patient partners, we will disseminate on social media and patient websites, to ensure that the results reach a relevant and diverse audience.

Lay abstract: Background_x000D_ Pain and disability after meniscectomy can be a substantial lifelong problem. Many of those affected are young and are severely impacted. They may also develop osteoarthritis (OA). Increasingly, surgeons are doing meniscal allograft transplants (MATs) for such people to reduce pain and improve function. This is thought to improve joint loading, reduce pain, and may prevent OA. However, MAT is expensive (around £7,500/case, totalling >£2M each year in the UK) and its clinical and cost-effectiveness are unproven. Non-surgical care including physiotherapy may be cheaper, safer and could be as or more effective. A randomised trial is urgently needed to determine which strategy is best for patients._x000D_ _x000D_ Research Question_x000D_ For people with pain after a meniscectomy but without established OA, does a decision to do MAT or best non-surgical care result in better clinical and/or cost effectiveness outcomes?_x000D_ _x000D_ Design_x000D_ A two-arm multi-centre pragmatic RCT of MAT compared to best non-surgical care, with internal pilot._x000D_ _x000D_ Health technologies_x000D_ MAT and post-operative physiotherapy versus a package of best non-surgical care called personalised knee therapy (PKT)._x000D_ _x000D_ Target Population_x000D_ Inclusion criteria: Pain and/or functional restriction from the knee, severe enough to warrant potential MAT; meniscectomy more than six months ago._x000D_ Exclusion criteria: Symptomatic ligament instability not previously corrected; Coronal limb alignment requiring surgical correction (previous correction is not an exclusion criteria); age under 16; full thickness cartilage loss >1cm2 on MRI; inflammatory arthritides; unable or unwilling to engage with rehabilitation; unable to adhere to trial processes._x000D_ _x000D_ Outcomes_x000D_ These have been established in close partnership with patients throughout study development._x000D_ Primary outcome: The four-domain Knee Osteoarthritis Outcome Score (KOOS4) at 24-months after randomisation, a well-established knee specific instrument._x000D_ Secondary Outcomes (baseline, 6, 12, 18 and 24 months after randomisation): All five KOOS domains, International Knee Documentation Committee subjective score, EQ-5D-5L (also at 3-months), Short Warwick-Edinburgh Mental Wellbeing Scale, Tegner activity/sport scale, work status (time off, change to work status), satisfaction, patient global impression of change, adverse events, further knee surgery and resource use._x000D_ _x000D_ Sample size_x000D_ We will recruit 144 participants over 29 months to detect a 10 point difference in the KOOS4 score with 90% power and 5% significance, assuming 20% loss to follow-up. The first 12 months of recruitment will be used to assess study recruitment, time to intervention and intervention compliance._x000D_ _x000D_ Impact and dissemination_x000D_ The results of this trial will have an important impact on patients for whom there are few good treatment options at present. MAT may be an effective solution, but if it is not then patients will avoid painful surgery with associated risks, and major savings will be made by stopping this expensive intervention. Clinical and cost-effectiveness results will be presented in high-impact journals and clinical conferences. With our PPI team members we will produce lay summaries and disseminate through patient organisations, on websites, and on social media. We will inform policy makers such as NICE. By delivering and disseminating a robust trial, we will ensure that the best care is offered for this under-researched patient group both in the UK and internationally.

Research activity codes: 6.4 SURGERY;6.7 PHYSICAL
Health categories: MUSCULOSKELETAL