A Randomized Trial of Autologous Chondrocyte Implantation Versus Alternative Forms of Surgical Cartilage Management in Patients With a Failed Primary Treatment for Chondral or Osteochondral Defects in the Knee
Martyn Snow, Lee Middleton, Samir Mehta, Andrew Roberts, Richard Gray, James B. Richardson, Jan Herman Kuiper, Anthony Smith, Steve White, Simon Roberts, David Griffiths, Aslam Mohammed, Kirti Moholkar, Tanweer Ashraf, Marcus Green, James Hutchinson, Tony Bhullar, Sanjeev Chitnis, Andrew Shaw, L. van Niekerk, A. Hui, Jon Olav Drogset, Gunnar Knutsen, Mike McNicholas, Mark Bowditch, David S. Johnson, P.G. Turner, Sanjiv Chugh, Neil T. Hunt, Salman Ali, Simon Palmer, Andrew Perry, Alastair Davidson, P Hill, Sunny Deo, Venkat Satish, M Radford, Ron Langstaff, David Houlihan-Burne, Dominic Spicer, Padman Phaltankar, Ahmed S. Hegab, David Marsh, Steve Cannon, Tim Briggs, Rob Pollock, Richard Carrington, John Skinner, George E. Bentley, Andrew Price, Peter Schranz, Vipul Mandalia, Shaun O’Brien
Abstract
Background: There are limited randomized controlled trials with long-term outcomes comparing autologous chondrocyte implantation (ACI) versus alternative forms of surgical cartilage management within the knee. Purpose: To determine at 5 years after surgery whether ACI was superior to alternative forms of cartilage management in patients after a failed previous treatment for chondral or osteochondral defects in the knee. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: In total, 390 participants were randomly assigned to receive either ACI or alternative management. Patients aged 18 to 55 years with one or two symptomatic cartilage defects who had failed 1 previous therapeutic surgical procedure in excess of 6 months prior were included. Dual primary outcome measures were used: (1) patient-completed Lysholm knee score and (2) time from surgery to cessation of treatment benefit. Secondary outcome measures included International Knee Documentation Committee and Cincinnati Knee Rating System scores, as well as number of serious adverse events. Analysis was performed on an intention-to-treat basis. Results: Lysholm scores were improved by 1 year in both groups (15.4 points [95% CI, 11.9 to 18.8] and 15.2 points [95% CI, 11.6 to 18.9]) for ACI and alternative, with this improvement sustained over the duration of the trial. However, no evidence of a difference was found between the groups at 5 years (2.9 points; 95% CI, −1.8 to 7.5; P = .46). Approximately half of the participants (55%; 95% CI, 47% to 64% with ACI) were still experiencing benefit at 5 years, with time to cessation of treatment benefit similar in both groups (hazard ratio, 0.97; 95% CI, 0.72 to 1.32; P > .99). There was a differential effect on Lysholm scores in patients with previous marrow stimulation compared with those without marrow stimulation ( P = .03; 6.4 points in favor of ACI; 95% CI, −0.4 to 13.1). More participants experienced a serious adverse event with ACI ( P = .02). Conclusion: Over 5 years, there was no evidence of a difference in Lysholm scores between ACI and alternative management in patients who had previously failed treatment. Previous marrow stimulation did not have a detrimental effect on the outcome of ACI. Registration: International Standard Randomised Controlled Trial Number: 48911177