Authors' objectives: We aimed to compare the clinical effectiveness, cost-effectiveness and complication rates of total ankle replacement with those of arthrodesis (i.e. ankle fusion) in the treatment of end-stage ankle osteoarthritis. More than 29,000 patients in the UK present to specialists each year with symptomatic end-stage ankle osteoarthritis, a condition in which the cartilage lining the ankle joint has worn away, causing progressive pain and stiffness. Ankle osteoarthritis causes major disability and has a similar impact on quality of life (QoL) as end-stage hip osteoarthritis and cardiac failure. The demand incidence for ankle osteoarthritis has been estimated at 47.7 per 100,000. The majority of this is secondary to trauma caused by fractures or severe sprains, both of which are increasing; hence, ankle osteoarthritis is likely to become an increasingly important health problem, especially among working adults. Other causes of ankle osteoarthritis include long-standing inflammatory arthropathies (e.g. rheumatoid arthritis, haemochromatosis and haemophiliac arthropathy). In the early stages of disease, non-operative measures such as a change in activity levels, weight loss, physiotherapy, painkillers and ankle braces should be used. When these conservative measures have failed, and a surgeon confirms the diagnosis of end-stage osteoarthritis on the basis of radiological and clinical evidence (i.e. plain radiographs and unrelenting symptoms, respectively), surgery might then be considered. Although arthrodesis (i.e. ankle fusion) is the most common surgical treatment for end-stage ankle osteoarthritis, in response to patient demand, more and more surgeons are performing total ankle replacement (TAR). At least 4000 patients are treated with ankle fusion or TAR each year in the NHS. The TARs implanted in England, Wales, Northern Ireland, the Isle of Man and Guernsey are captured on the National Joint Registry, which has revision surgery as its end point. The British Orthopaedic Foot & Ankle Society only recently started capturing outcome data on ankle fusion patients. All studies comparing TAR with ankle fusion to date have been observational and, to the best of our knowledge, there have been no high-quality prospective randomised trials reported. The total ankle replacement versus ankle arthrodesis (TARVA) trial aimed to compare the clinical effectiveness and cost-effectiveness of TAR with that of ankle fusion for the treatment of end-stage ankle osteoarthritis in patients aged 50–85 years. Clinical effectiveness was measured through self-reported pain-free function using a standardised questionnaire of walking and standing ability 52 weeks post surgery. We also aimed to determine whether or not there was a difference in physical function [measured using the Foot and Ankle Ability Measure – Activities of Daily Living (FAAM-ADL)], QoL [measured using the EuroQol 5-Dimensions, five-level version (EQ-5D-5L)] and range of ankle motion at 26 and 52 weeks post surgery. We investigated the cost-effectiveness and cost–utility of TAR and ankle fusion.

Authors' results and conclusions: Between March 2015 and January 2019, 303 participants were randomised using a minimisation algorithm: 152 to total ankle replacement and 151 to ankle fusion. At 52 weeks, the mean (standard deviation) Manchester–Oxford Foot Questionnaire walking/standing domain score was 31.4 (30.4) in the total ankle replacement arm (n = 136) and 36.8 (30.6) in the ankle fusion arm (n = 140); the adjusted difference in the change was –5.6 (95% confidence interval –12.5 to 1.4; p = 0.12) in the intention-to-treat analysis. By week 52, one patient in the total ankle replacement arm required revision. Rates of wound-healing issues (13.4% vs. 5.7%) and nerve injuries (4.2% vs. < 1%) were higher and the rate of thromboembolic events was lower (2.9% vs. 4.9%) in the total ankle replacement arm than in the ankle fusion arm. The bone non-union rate (based on plain radiographs) in the ankle fusion arm was 12.1%, but only 7.1% of patients had symptoms. A post hoc analysis of fixed-bearing total ankle replacement showed a statistically significant improvement over ankle fusion in Manchester–Oxford Foot Questionnaire walking/standing domain score (–11.1, 95% confidence interval –19.3 to –2.9; p = 0.008). We estimate a 69% likelihood that total ankle replacement is cost-effective compared with ankle fusion at the National Institute for Health and Care Excellence’s cost-effectiveness threshold of £20,000 per quality-adjusted life-year gained over the patient’s lifetime. Both total ankle replacement and ankle fusion improved patients’ quality of life at 1 year, and both appear to be safe. When total ankle replacement was compared with ankle fusion overall, we were unable to show a statistically significant difference between the two arms in terms of our primary outcome measure. The total ankle replacement versus ankle arthrodesis (TARVA) trial is inconclusive in terms of superiority of total ankle replacement, as the 95% confidence interval for the adjusted treatment effect includes both a difference of zero and the minimal important difference of 12, but it can rule out the superiority of ankle fusion. A post hoc analysis comparing fixed-bearing total ankle replacement with ankle fusion showed a statistically significant improvement of total ankle replacement over ankle fusion in Manchester–Oxford Foot Questionnaire walking/standing domain score. Total ankle replacement appears to be cost-effective compared with ankle fusion at the National Institute for Health and Care Excellence’s cost-effectiveness threshold of £20,000 per quality-adjusted life-year gained over a patient’s lifetime based on long-term economic modelling. Baseline characteristics Between March 2015 and January 2019, 303 participants were randomised; 282 participants had surgery and 281 attended at least one follow-up visit. The mean age was 68 years, 71% of participants were male and 43% had arthritis in one or more adjacent joints. The arms were well balanced at baseline, as observed from the baseline characteristics. Both TAR and ankle fusion improved patients’ QoL at 1 year, but we did not show one to be superior in terms of clinical scores at 52 weeks when using either ITT or per-protocol analysis. The TARVA trial is inconclusive in terms of the superiority of TAR, as the 95% CI for the adjusted treatment effect includes both a difference of zero and the MID of 12. However, we can rule out the superiority of ankle fusion. Both operations appear to be safe. A post hoc analysis of the most common type of implant in the UK, the fixed-bearing TAR, did show a statistically significant improvement of TAR over ankle fusion, suggesting that fixed-bearing TAR may outperform ankle fusion. There is a 69% probability of TAR being cost-effective compared with ankle fusion at the NICE cost-effectiveness threshold £20,000 per QALY gained over patients’ lifetime.

Authors' recommendations: Between March 2015 and January 2019, 303 participants were randomised using a minimisation algorithm: 152 to total ankle replacement and 151 to ankle fusion. At 52 weeks, the mean (standard deviation) Manchester–Oxford Foot Questionnaire walking/standing domain score was 31.4 (30.4) in the total ankle replacement arm (n = 136) and 36.8 (30.6) in the ankle fusion arm (n = 140); the adjusted difference in the change was –5.6 (95% confidence interval –12.5 to 1.4; p = 0.12) in the intention-to-treat analysis. By week 52, one patient in the total ankle replacement arm required revision. Rates of wound-healing issues (13.4% vs. 5.7%) and nerve injuries (4.2% vs. < 1%) were higher and the rate of thromboembolic events was lower (2.9% vs. 4.9%) in the total ankle replacement arm than in the ankle fusion arm. The bone non-union rate (based on plain radiographs) in the ankle fusion arm was 12.1%, but only 7.1% of patients had symptoms. A post hoc analysis of fixed-bearing total ankle replacement showed a statistically significant improvement over ankle fusion in Manchester–Oxford Foot Questionnaire walking/standing domain score (–11.1, 95% confidence interval –19.3 to –2.9; p = 0.008). We estimate a 69% likelihood that total ankle replacement is cost-effective compared with ankle fusion at the National Institute for Health and Care Excellence’s cost-effectiveness threshold of £20,000 per quality-adjusted life-year gained over the patient’s lifetime. Both total ankle replacement and ankle fusion improved patients’ quality of life at 1 year, and both appear to be safe. When total ankle replacement was compared with ankle fusion overall, we were unable to show a statistically significant difference between the two arms in terms of our primary outcome measure. The total ankle replacement versus ankle arthrodesis (TARVA) trial is inconclusive in terms of superiority of total ankle replacement, as the 95% confidence interval for the adjusted treatment effect includes both a difference of zero and the minimal important difference of 12, but it can rule out the superiority of ankle fusion. A post hoc analysis comparing fixed-bearing total ankle replacement with ankle fusion showed a statistically significant improvement of total ankle replacement over ankle fusion in Manchester–Oxford Foot Questionnaire walking/standing domain score. Total ankle replacement appears to be cost-effective compared with ankle fusion at the National Institute for Health and Care Excellence’s cost-effectiveness threshold of £20,000 per quality-adjusted life-year gained over a patient’s lifetime based on long-term economic modelling. Baseline characteristics Between March 2015 and January 2019, 303 participants were randomised; 282 participants had surgery and 281 attended at least one follow-up visit. The mean age was 68 years, 71% of participants were male and 43% had arthritis in one or more adjacent joints. The arms were well balanced at baseline, as observed from the baseline characteristics. Both TAR and ankle fusion improved patients’ QoL at 1 year, but we did not show one to be superior in terms of clinical scores at 52 weeks when using either ITT or per-protocol analysis. The TARVA trial is inconclusive in terms of the superiority of TAR, as the 95% CI for the adjusted treatment effect includes both a difference of zero and the MID of 12. However, we can rule out the superiority of ankle fusion. Both operations appear to be safe. A post hoc analysis of the most common type of implant in the UK, the fixed-bearing TAR, did show a statistically significant improvement of TAR over ankle fusion, suggesting that fixed-bearing TAR may outperform ankle fusion. There is a 69% probability of TAR being cost-effective compared with ankle fusion at the NICE cost-effectiveness threshold £20,000 per QALY gained over patients’ lifetime.

Authors' methods: This was a pragmatic, multicentre, parallel-group, non-blinded randomised controlled trial. Patients with end-stage ankle osteoarthritis who were aged 50–85 years and were suitable for both procedures were recruited from 17 UK hospitals and randomised using minimisation. The primary outcome was the change in the Manchester–Oxford Foot Questionnaire walking/standing domain scores between the preoperative baseline and 52 weeks post surgery. This initial report contains only 52-week data, which must therefore be interpreted with caution. In addition, the pragmatic nature of the study means that there was heterogeneity between surgical implants and techniques. The trial was run across 17 NHS centres to ensure that decision-making streams reflected the standard of care in the NHS as closely as possible. Design We conducted a pragmatic prospective, multicentre, parallel-group, non-blinded randomised controlled trial (RCT). Participants were randomised equally between two arms: TAR and ankle fusion. The study protocol [Goldberg AJ, Zaidi R, Thomson C, Doré CJ, Skene SS, Cro S, et al. Total ankle replacement versus arthrodesis (TARVA): protocol for a multicentre randomised controlled trial. BMJ Open 2016;6:e012716] was developed before recruitment commenced and detailed the design, interventions and study procedures. The trial was conducted across 17 participating UK sites. Patients with end-stage ankle osteoarthritis who were aged 50–85 years and who the surgeon believed were suitable for both TAR and ankle fusion were eligible to join the trial. Patients had to be able to read and understand the patient information sheet (PIS) and provide written consent on an informed consent form (ICF). At randomisation patients were allocated to receive either TAR or ankle fusion. For TAR, the remaining damaged cartilage was removed and the joints resurfaced with metal implants and an intervening polyethylene liner, either fixed or mobile bearing, to act as a gliding surface. All prostheses were CE marked. For ankle fusion, the remaining damaged cartilage was removed from the ends of the bone and the two bones held together in compression using screws or plates to join them as one bone (bone fusion) so that there was no longer any movement at the tibiotalar joint. Participants were seen at recruitment, randomisation, surgery visit and at 2, 6, 12, 26 and 52 weeks post surgery.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/hta/PTYJ1146

Year Published: 2023

URL for published report: https://njl-admin.nihr.ac.uk/document/download/2042159

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/PTYJ1146

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk