Title: Knee Arthroplasty versus Joint Distraction Study (KARDS) for Osteoarthritis
Funder: Department of Health and Social Care

Abstract: This summary was written with input from 3 lay members. _x000D_ _x000D_ Knee Osteoarthritis (OA) is a common disabling condition of older people (>45) that causes pain, stiffness, & disability symptoms which limit day-to-day activities such as walking, using stairs & disturbs sleep. People living longer, desire to stay active & increasing obesity have contributed to more people having knee OA. _x000D_ Treatment for knee OA initially includes weight loss advice, physiotherapy & exercises, together with pain-killers, supports (insoles or braces) & steroid injections. When these treatments fail to control symptoms, patients are referred to a specialist for further management. Depending on the symptoms and x-ray findings, a knee replacement (KR) may be offered. In 2015-16 over 100,000 KRs were carried out in the UK at a cost to the NHS of over £1 billion._x000D_ _x000D_ In a KR, the damaged parts of the knee are removed & replaced with metal and plastic (known as a prosthesis). Although most people after a KR experience substantial improvement in their symptoms, pain relief is variable and one in five patients continue to suffer with pain or are dissatisfied. With time; artificial joints fail particularly in the young and/or active. Replacement of a failed KR is complex and associated with higher risks and less predictable outcomes. KR is therefore not the preferred treatment option for people who are likely to outlive their artificial knee. A recent study of the national practice showed that in people aged under 60 the average time to KR failure was just 4.5 years. There is a pressing need for alternative treatment for knee OA._x000D_ _x000D_ One such treatment is knee joint distraction (KJD), where the damaged parts of the native knee are not removed, but instead allow healthy cartilage to heal which keeps the joint pain free. This is achieved by the joint being pulled apart (distraction) by a device containing metal tubes on the outside of the knee which are fixed in place using metal pins into both the shin and thigh bone. This process removes the weight normally experienced by the worn knee preventing further damage, allowing a healing process to begin. The leg is maintained in a fixed position for 6 weeks and crutches are needed for walking. This intervention has been performed on over 120 patients in the Netherlands. These patients have experienced reduced pain, retained mobility & have not needed a KR for at least 5 years post-surgery in around 80% of cases. KJD seems to be a suitable & promising treatment for young & active patients as it does not prevent a future KR if needed but can reduce the need / delay the time a patient will need one. However, KJD is currently not available in the UK._x000D_ _x000D_ In this research, patients with severe knee OA, who consent to take part, will be randomly allocated either knee joint distraction or knee replacement. 344 patients will be recruited in this multi-centre study across the UK. Both patient groups will be monitored and their experience compared over two years with regular clinic visits, x-rays and questionnaires. In addition, we will establish the need for further surgery. An analysis of the cost-effectiveness of treating patients with KJD versus KR will be performed to see if this could represent value for money for the NHS in the coming years where the number of patients with knee OA is set to increase substantially._x000D_ _x000D_ We will keep people & patient groups informed of our findings & be guided by their suggestions.

Lay abstract: One in three knee replacements (KR) in the UK are performed in patients aged 65 or under. The estimated life time revision risk in this age group is two to seven times higher as compared to those over 70. Any treatment that avoids or delays KR in this population, presents a significant opportunity to avoid the morbidity, mortality & costs associated with revision surgery._x000D_ _x000D_ Knee Joint Distraction (KJD), where the joint is held apart by an external fixator, is one such treatment. Its use in knee OA is associated with significant improvements in symptoms & restoration of cartilage thickness. Observational studies have reported the benefits of KJD to extend to beyond five years, with a low conversion rate to KR. With an RCT (n=56) in patients aged 65 or under, outcomes following KJD were not statistically different at one year post-surgery compared to KR. Whilst a high pin site infection rate has been reported with KJD (69% (95%CI 51 to 87)), the vast majority of these are successfully managed with antibiotics. KJD may represent a safe alternative to KR. Although these results are promising, they are based on small studies, from a single centre. Furthermore, the pain reduction in KJD is less than that in KR, however, patients seem to tolerate the residual symptoms & the need for the KR is postponed. This has informed the non-inferiority (NI) design of our study._x000D_ _x000D_ Knee ARthroplasty vs Distraction Study (KARDS) is a pragmatic, two-arm NI multi-centre trial designed to establish the clinical & cost-effectiveness of KJD in a NHS setting. Inclusion criteria are adults aged 65 years or under, with symptomatic knee OA refractory to conservative management and severe enough to warrant a KR with intact collateral ligaments & alignment not requiring correction. Exclusion criteria are inflammatory arthritis, existing arthroplasty, ankylosis, Kellgren Lawrence Grade 4 OA in both tibiofemoral compartments, surgery on involved knee within the past 6 months (excluding arthroscopy) & history of osteoporosis or fragility fracture._x000D_ _x000D_ The primary outcome is the Knee Injury & Osteoarthritis Outcomes Score (KOOS) pain component measured at 12 months following surgery. Secondary outcomes include PROMs (KOOS, Oxford Knee Score, EQ5D-5L) within 24 months, as well as functional assessments (timed up & go test & range of motion), radiographic assessment (joint space width evaluated using standardised radiographs) & assessment of surgical complications, including infection rates. Cost-effectiveness using a health economic modelling approach will estimate costs based on a 20-year horizon. This study also offers a unique mechanism to establish 5-year joint survival by accessing routinely collected national joint registry data. We will ask the participants to consent for this at the time of recruitment. _x000D_ _x000D_ A sample size of 344 (172 per treatment arm) will provide 90% power, 2.5% significance (one-sided), to demonstrate non-inferiority with a NI limit defined as a 8 points reduction, assuming variability (SD) of 21 and allowing for 15% drop-out rate. Randomisation will be stratified by centre & OA severity._x000D_ _x000D_ PROJECT TIMELINES: Total 66 months: set-up 9 months; recruitment 27 months (including internal pilot of 12 months); follow-up 24 months; analysis 6 months. Average recruitment rate of 1 patient /centre /month across 20 centres. Across participating centres around 30 patients/month undergo KR & we consider a 3% recruitment rate is realistic & achievable.

Research activity codes: 6.4 SURGERY
Health categories: MUSCULOSKELETAL