Title: What is the clinical-effectiveness and cost-effectiveness of surgery with medial opening wedge high tibial osteotomy (HTO) compared with non-surgical treatment in the management of osteoarthritis (OA) of the knee in patients younger than 60 years? (MOTION Trial)
Funder: Chief Scientist Office, Scotland

Abstract: BACKGROUND_x000D_ Osteoarthritis (OA) is the leading cause of disability worldwide. The knee joint is the most common site of OA. Nearly 1 in 5 people >45 years in the UK will seek treatment for it. In a healthy knee joint, there is a smooth lining that covers the ends of the bones. In knee OA, this smooth lining thins, roughens and is permanently damaged causing joint pain, swelling and stiffness. Patients have a reduced quality of life as they struggle with daily activities like walking, standing and sleeping and often cannot work due to the disability. Initial treatment is non-surgical with general advice, painkillers, walking aids, physiotherapy and occasionally, steroid injections. If the knee is still painful, surgery may be considered. If patients are >60 years then knee replacement surgery is successful as the diseased part of the knee is physically removed and replaced with an artificial implant. However, in patients <60 years knee replacement surgery is less successful because the metal/plastic knee implant wears out much sooner due to higher activity levels in young, working age patients. The artificial joint has to be replaced again, sometimes several times, and patients have to go through complex, risky repeat operations. Most patients do not return to work either. In patients<60 years, it is therefore best to delay knee replacement surgery as long as possible, and other treatments should be considered instead. There is an option whereby the knee can be realigned without the need for replacing it. During this surgery called ‘high tibial osteotomy’, the bone is cut just below the knee joint and a small wedge is opened, to shift the person’s weight away from the damaged part of the knee to a healthy part of the knee. By ‘unloading’ the damaged part of the knee, the surgery can decrease pain, improve function and delay the need for knee replacement or avoid it altogether. It may allow many more young patients to return to work. However, we also do not know if delaying or avoiding knee replacement surgery in patients <60 years with high tibial osteotomy surgery is any better than non-surgical treatment alone, as the two options have never been compared._x000D_ _x000D_ AIM_x000D_ We wish to study whether treating a painful, arthritic knee joint in patients younger than 60 years with joint realignment surgery (called high tibial osteotomy) is better than non-surgical treatment in terms of pain relief, improved quality of life and ability to return to work._x000D_ _x000D_ METHODS_x000D_ In this study 224 patients under 60 years with knee OA will be selected to compare the two possible options (non-surgical vs high tibial osteotomy) using a type of study called a randomised trial. Which of the two treatments patients will get will be decided by chance, using a computer - half the patients will get one treatment, and half will get the other. To compare, we will ask patients about their pain, knee function, quality of life and ability to work after the treatment. The research will be carried out at the local hospital or institution where the patient would normally be seen and treated. Measurements will be taken in clinic. Patient based questionnaires will be sent via post or email to assess which treatment is better. The questionnaires directly assess how the patient, rather than the surgeon, feels about the outcome after their treatment. _x000D_ _x000D_ PATIENT & PUBLIC INVOLVEMENT (PPI)_x000D_ We have worked in partnership with a dedicated patient group with lived experience of knee osteoarthritis and high tibial osteotomy surgery, to help develop this proposal from the start. Their feedback has encouraged us that the question is important and has substantially influenced the study. Members of this patient group will be closely involved with the running of this study throughout its course over the next 5 years and are also embedded within the project oversight and management committees._x000D_ _x000D_ DISSEMINATION_x000D_ The results of this study will be advertised via press releases (radio, TV and newspapers), social media, national/international meetings and journal publications.

Lay abstract: BACKGROUND_x000D_ Nearly 1 in 5 people >45 years in the UK suffer from pain and disability due to knee osteoarthritis (OA). This number is expected to increase dramatically over the next two decades. The James Lind Alliance designated the surgical and non-surgical options for the treatment of knee OA as a Top 10 Priority Setting Partnership in 2016. In patients >60 years with moderate-to-severe knee OA, surgery with knee replacement (partial or total) has been successful. However, in patients <60 years there is uncertainty regarding the most effective treatment (surgical or non-surgical) because knee replacement in these patients is associated with a high failure rate, poor patient reported outcome scores, low rates of return to work and high rates of redo knee replacement. If the knee OA mainly affects the medial compartment of the knee, realignment of the lower leg with high tibial osteotomy (HTO) can also relieve pain and improve function with the possibility of return to work. Since the native knee joint is preserved in HTO, it has the potential to be an effective surgical solution in active patients <60 years with the aim of delaying knee replacement until they are >60 years when results of knee replacement become more predictable. In a proportion of patients undergoing HTO surgery, knee replacement may be avoided altogether. However, surgical treatment with HTO has never been compared with non-surgical treatment. This trial is aimed at filling this evidence gap._x000D_ _x000D_ RESEARCH QUESTIONS_x000D_ (1) For patients <60 years with medial compartment knee OA, what is the relative clinical effectiveness (pain relief, improvement in function, quality of life, return to work) of HTO compared with non-surgical management at 24 months?_x000D_ (2) For patients <60 years with medial compartment knee OA, what is the relative cost-effectiveness of HTO compared to non-surgical management at 24 months and as modelled over a lifetime horizon? _x000D_ _x000D_ AIM_x000D_ The aim of this trial is to conduct a pragmatic, multicentre, randomised controlled trial to determine whether the intervention is superior to comparator._x000D_ _x000D_ METHODS_x000D_ 224 patients will be recruited across 20 NHS sites and will be randomly assigned (1:1 ratio) to one of two treatment arms - surgical treatment with HTO or non surgical treatment. The PICO framework for the study is as follows:_x000D_ Population - NHS patients <60 years with symptomatic knee OA localised to the medial compartment in whom surgical intervention is indicated. _x000D_ Intervention - Surgery with medial opening wedge HTO followed by standard postoperative rehabilitation based on local pathways._x000D_ Comparator - Non-surgical intervention with Personalised Knee Therapy (PKT) delivered within an NHS physiotherapy department. The PKT will be delivered within 6-contact sessions over a period not exceeding 4 months. A core package will focus on education and advice, pain moderation, structured exercise/rehabilitation with optional additional treatment of co-existing symptoms, manual therapy, use of steroid injections and bracing/orthotics based on local pathways. _x000D_ Outcomes - The primary outcome will be the 24-month Knee Injury and Osteoarthritis Outcome Score (KOOS). The secondary outcome measures will be the Oxford Knee Score, Forgotten Joint Score-12, EuroQol EQ-5D-3L score, Pittsburgh Sleep Problem Scale, Return to work/employment questionnaire, additional study knee related operative interventions, complications and health economic evaluation at 12 and 24 months following randomisation. _x000D_ _x000D_ For the health economic evaluation, two complimentary cost-effectiveness analyses will be performed: (1) A 24-month within trial analysis, and (2) A decision analytic simulation model to account for the impacts of future knee replacements (and associated revisions), and their timing relative to retirement and employment potential. An integrated mixed method process evaluation will assess the acceptability and feasibly of the intervention from staff and patients to address the following research objectives: (1) explore trial eligibility, recruitment and retention rates (2) acceptability of intervention implementation including trial processes and the collection of routine monitoring data (3) patient experience of taking part and the contextual factors that influence this._x000D_ _x000D_ STUDY TIMELINE_x000D_ 0-6 months - approvals/set up_x000D_ 6-30 months - set up 20 NHS sites, complete recruitment including 9-month 5-site internal pilot, recruitment rate of 0.7 patients/site/month_x000D_ 30-54 months - complete 24 month follow-up for all participants_x000D_ 54-60 months - complete analyses, report writing and dissemination of results_x000D_ _x000D_ ANTICIPATED IMPACT_x000D_ Short-term impact on the treatment of all patients <60 years in the UK who need surgery for knee OA each year. Long-term impact on total numbers of knee replacements or HTOs performed in patients <60 years as recorded by existing UK registries and NHS digital data that inform patients, clinicians and healthcare providers. The British Association for Surgery of the Knee (BASK) supports this study.

Research activity codes: 6.4 SURGERY
Health categories: MUSCULOSKELETAL