Genicular Artery Embolisation for the symptomatic treatment of knee osteoarthritis refractory to conservative management (GEKO)

Research question In patients with painful knee osteoarthritis, is genicular artery embolisation effective at reducing pain at 6 months post-randomisation, compared to a placebo intervention? Background: Osteoarthritis (OA) is the commonest cause of musculoskeletal pain in the UK, affecting up to 1 in 6 adults, with over a million living in severe pain. Despite following the NICE guidance for managing OA, many patients are in the ‘treatment gap’ being ineligible for surgery but without an effective treatment option. The cause of knee pain in OA is complex involving synovitis, inflammation and the formation of abnormal new blood vessels and nerve-endings. This has led to the hypothesis that selectively occluding these abnormal new vessels by Genicular Artery Embolisation (GAE) can reduce hypervascularity and therefore reduce patient’s pain. A number of published pilot studies have provided encouraging evidence of GAE’s clinical benefit. However, no published randomised controlled trials (RCTs) exist providing fundamental proof of efficacy and no studies have linked a reduction in hypervascularity to pain reduction. Aims and objectives: The overall aim of this study is to assess the efficacy and mechanism of action of genicular artery embolisation in treating patients with knee OA that is refractory to NICE recommended treatments. Our specific objectives are to answer the following questions: 1. In patients with painful knee OA, is GAE effective at reducing pain at 6 months post-randomisation, compared to a placebo intervention? 2. Following GAE is there a reduction in synovial hypervascularity and synovitis within the knee? 3. Is the outcome of GAE dependent on the degree of OA damage within the knee? Methods: The study will be a multi-centre 2-armed parallel group superiority design RCT, with 1:1 allocation, comparing the clinical efficacy of GAE with a high-fidelity placebo procedure. The primary outcome measure will be patient reported pain using a validated visual analogue scale (VAS), measured at 6 months. The study will recruit 216 subjects from 10-12 centres to achieve 90% power. In addition, we have embedded secondary mechanistic biomarker outcomes, taking advantage of the controlled placebo trial methodology to investigate the link between synovitis, hypervascularity and knee pain in OA using standard and contrast-enhanced MRI. Timelines for delivery: The study will take 44 months to complete. This involves a period for initial trial set-up and internal pilot recruitment. Full recruitment will end by 26 months. Completion of primary time point data collection will end at 32 months and extended follow-up at 38 months, leaving 6 month for final analysis, write-up and dissemination. Anticipated impact and dissemination: The most important output of this work is to produce evidence that demonstrates the efficacy of GAE as a treatment for knee OA that is resistant to current clinical care. This would be a major step-forward for the many thousands of patients who suffer from this disabling medical condition and the impact on one of the most common musculoskeletal problems would be dramatic. The findings will be actively disseminated with all stakeholders – patients, NHS, NICE, clinicians, OA researchers.