Ankle Osteoarthritis: Successful Completion of a Challenging Clinical Trial Comparing Surgical Treatments

In their article, Goldberg and colleagues (1) report a trial that was likely challenging to execute—a pragmatic, randomized, multicenter trial of surgical treatments for patients with end-stage ankle osteoarthritis. Although randomized trials are often considered the “gold standard” for determining treatment success by reducing known and unknown selection biases, the number of randomized trials of surgical interventions is limited. Standardizing surgical interventions, difficulties with blinding, ethical concerns, and surgeon and patient reluctance to participate are all substantial barriers to such trials (2, 3). Trials of surgical interventions can be especially difficult to execute when 2 treatments have characteristics that are distinguishable, as in Goldberg and colleagues' study. Ankle arthritis is far less well studied than hip and knee arthritis, yet it has similar deleterious effects on quality of life and function (4, 5). Ankle arthritis is also less prevalent than hip and knee arthritis, creating another challenge to comparative effectiveness. The number of ankle replacements performed has increased dramatically over the past 2 decades (6). Prior prospective observational studies have had conflicting results, with some showing no difference and others favoring total ankle replacement over fusion (7, 8). Goldberg and colleagues overcame substantial challenges to provide amore definitive comparison of the procedures. Reluctance to be randomized and a relatively low prevalence were addressed by including 17 centers with surgeons willing to participate. Despite clinical equipoise, 1604 patients were screened to identify 933 eligible, of whom 603 did not consent, for a participation rate of 35%. The article does not describe the characteristics of those eligible who did not participate to explore whether there was potential participation bias related to factors that may influence the outcomes. However, this participation rate is not unusual for surgical trials. Assembling 17 centers creates a degree of heterogeneity of implants and surgeon level of experience. A prior study showed that the first 10 ankle replacements a surgeon performs have a higher rate of technical errors (9). This was addressed by requiring completion of 20 procedures before the study to attempt to better match care to that outside of a clinical trial. Remarkably, there were only 4 crossover patients, all from the fusion group to the replacement group. This is a credit to the investigators who presumably communicated very clearly to the patients. Although 52-week follow-up is insufficient to define long-term comparative effectiveness, it does allow comparison of perioperative adverse events and early return to function, providing a foundation for long-term outcomes. Surgical treatment of ankle arthritis is intended to improve function and reduce pain for years to decades. We look forward to the investigators' continued assessment of the trial participants to compare outcomes over the long term. Nonetheless, the shorter-term findings reported in this article are interesting and point to areas for future research. There was no statistically significant difference between fusion and replacement in the primary outcome at 1 year. In secondary analyses, total ankle replacement seemed to yield better outcomes in patients with surrounding joint arthritis. This previously unsubstantiated belief was a driver for advancing ankle arthroplasty because ankle fusion performs less well when the surrounding joints are fused or arthritic. If sample size permits, the heterogeneity of implants used during the trial may enable some insight into implant design. A secondary finding reported is that the type of ankle implant may make a difference. Some implants have 2 motion segments, and some have only 1. Prior data have suggested that 3-component implants may perform less well, but it was not level 1 evidence. In this study, those that received fixed total ankle replacement implants had greater improvement than those with mobile bearing implants or ankle fusions. This potentially important finding warrants further scrutiny. We congratulate Goldberg and colleagues for this major contribution to identifying the optimal treatment of patients with debilitating ankle arthritis.