Authors' objectives: Anterior cruciate ligament injury of the knee is common and leads to decreased activity and risk of secondary osteoarthritis of the knee. Management of patients with a non-acute anterior cruciate ligament injury can be non-surgical (rehabilitation) or surgical (reconstruction). However, insufficient evidence exists to guide treatment. To determine in patients with non-acute anterior cruciate ligament injury and symptoms of instability whether a strategy of surgical management (reconstruction) without prior rehabilitation was more clinically and cost-effective than non-surgical management (rehabilitation). Anterior cruciate ligament (ACL) injury is a common knee injury that can have a profound effect on knee kinematics (knee movement and forces) with recurrent knee instability as the main problem. This leads to poor quality of life (QoL), decreased activity and increased risk of secondary osteoarthritis of the knee. Management of patients with an ACL injury can include a non-surgical (rehabilitation) or surgical (reconstruction) approach. The rehabilitation involves specialised physiotherapy exercises, while the surgery involves reconstructing the ligament, usually with tissue taken from the injured persons own body (autograft). However, insufficient and conflicting evidence exists to show which of these management strategies is best in order to guide decision-making and treatment. High-quality trials have been conducted in the management of acutely injured patients with conflicting findings. A Scandinavian study suggested that rehabilitation should always be attempted in the first place for acute cases, whereas a subsequent Dutch study showed that ACL reconstruction (ACLR) gave better results. In the NHS patients often present late for diagnosis and management and the results of these two studies cannot be applied to the longer-standing ACL-injured population often seen in the UK. A randomised trial was designed to address the uncertainty and fill the gap in the evidence base regarding the clinical and cost effectiveness of these two approaches. The intention was to inform standards of care for ACL injury management in non-acute patients. To determine in patients with non-acute ACL injury [commonly referred to as ACL deficiency (ACLD)] whether a strategy of surgical management (reconstruction) without prior rehabilitation was more clinically effective and cost-effective than non-surgical management (rehabilitation with option for later ACLR only if required). The primary end point was a functional knee score at 18-month follow-up from randomisation. Design The study was a pragmatic, multicentre, superiority, randomised controlled trial with two-arm parallel groups and 1:1 allocation. A two-stage internal pilot study was included to confirm appropriateness of inclusion criteria, assess outcome measures and data capture systems, and ensure adequate recruitment. Rather than a head-to-head comparison of two interventions, the study was designed as a ‘management’ assessment in which specific events were expected and permitted. This included the subsequent requirement for necessary surgical intervention (ACLR) in patients first allocated to the rehabilitation arm. Both intention-to-treat (ITT) and per-protocol analyses were planned. Due to the nature of the interventions, there was no blinding of the participants nor healthcare practitioners (surgeons and physiotherapists) to receipt of the intervention.

Authors' results and conclusions: Three hundred and sixteen participants were recruited between February 2017 and April 2020 with 156 randomised to surgical management and 160 to rehabilitation. Forty-one per cent (n = 65) of those allocated to rehabilitation underwent subsequent reconstruction within 18 months with 38% (n = 61) completing rehabilitation and not undergoing surgery. Seventy-two per cent (n = 113) of those allocated to surgery underwent reconstruction within 18 months. Follow-up at the primary outcome time point was 78% (n = 248; surgical, n = 128; rehabilitation, n = 120). Both groups improved over time. Adjusted mean Knee Injury and Osteoarthritis Outcome Score 4 scores at 18 months had increased to 73.0 in the surgical arm and to 64.6 in the rehabilitation arm. The adjusted mean difference was 7.9 (95% confidence interval 2.5 to 13.2; p = 0.005) in favour of surgical management. The per-protocol analyses supported the intention-to-treat results, with all treatment effects favouring surgical management at a level reaching statistical significance. There was a significant difference in Tegner Activity Score at 18 months. Sixty-eight per cent (n = 65) of surgery patients did not reach their expected activity level compared to 73% (n = 63) in the rehabilitation arm. There were no differences between groups in surgical complications (n = 1 surgery, n = 2 rehab) or clinical events (n = 11 surgery, n = 12 rehab). Of surgery patients, 82.9% were satisfied compared to 68.1% of rehabilitation patients. Health economic analysis found that surgical management led to improved health-related quality of life compared to non-surgical management (0.052 quality-adjusted life-years, p = 0.177), but with higher NHS healthcare costs (£1107, p 

Authors' methods: A pragmatic, multicentre, superiority, randomised controlled trial with two-arm parallel groups and 1:1 allocation. Due to the nature of the interventions, no blinding could be carried out. Twenty-nine NHS orthopaedic units in the United Kingdom. Participants with a symptomatic (instability) non-acute anterior cruciate ligament-injured knee. Patients in the surgical management arm underwent surgical anterior cruciate ligament reconstruction as soon as possible and without any further rehabilitation. Patients in the rehabilitation arm attended physiotherapy sessions and only were listed for reconstructive surgery on continued instability following rehabilitation. Surgery following initial rehabilitation was an expected outcome for many patients and within protocol. The primary outcome was the Knee Injury and Osteoarthritis Outcome Score 4 at 18 months post randomisation. Secondary outcomes included return to sport/activity, intervention-related complications, patient satisfaction, expectations of activity, generic health quality of life, knee-specific quality of life and resource usage. Not all surgical patients underwent reconstruction, but this did not affect trial interpretation. The adherence to physiotherapy was patchy, but the trial was designed as pragmatic. The study was a pragmatic, multicentre, superiority, randomised controlled trial with two-arm parallel groups and 1:1 allocation. A two-stage internal pilot study was included to confirm appropriateness of inclusion criteria, assess outcome measures and data capture systems, and ensure adequate recruitment. Rather than a head-to-head comparison of two interventions, the study was designed as a ‘management’ assessment in which specific events were expected and permitted. This included the subsequent requirement for necessary surgical intervention (ACLR) in patients first allocated to the rehabilitation arm. Both intention-to-treat (ITT) and per-protocol analyses were planned. Due to the nature of the interventions, there was no blinding of the participants nor healthcare practitioners (surgeons and physiotherapists) to receipt of the intervention. Twenty-nine secondary care NHS orthopaedic units from across the UK. The study involved 87 surgeons and 205 physiotherapists. The inclusion criteria included any patient aged 18 years or above with symptomatic ACLD of the native ligament (instability episodes of frank giving way or feeling unstable) with the ACL injury (either partial or complete tear) confirmed using clinical assessment and magnetic resonance imaging (MRI) scan. Patients were excluded if they were in the acute phase of primary ACL injury, have had previous knee surgery to the index knee, had meniscal pathology with characteristics that indicate immediate surgery, or any features of late-stage osteoarthritis. Three hundred and sixteen trial participants with a symptomatic non-acute ACL-injured knee were randomised between February 2017 and April 2020. One hundred and fifty-six participants were randomised to the surgical management arm and 160 to the rehabilitation arm. Patients in the surgical management arm underwent arthroscopic ACLR (using any technique chosen by the surgeon) as soon as possible and without any further formal or prescribed rehabilitation. Patients in the rehabilitation arm (non-surgical) attended rehabilitation sessions at a local physiotherapy department and only were listed for reconstructive surgery on continued instability or symptoms following rehabilitation. Standard postoperative rehabilitation was provided and some assessment of compliance was conducted. Guidance was provided on a minimal rehabilitation protocol for all rehabilitation sites to enable a level of quality control/standardisation without disrupting the pragmatic nature of the study. Compliance and fidelity data were also collected for both surgery and rehabilitation interventions. There were several limitations to the study, but these did not affect the interpretation. Firstly, not all surgical patients underwent reconstruction, but an ITT analysis still showed a significant difference (and was aligned with per-protocol analyses). Early adjustment of inclusion criteria to facilitate recruitment generated a sample that tended towards a more acute population than ideal but was still considered representative of the intended population. The hierarchy of treatment could have posed problems in this surgical versus non-surgical study (non-surgical treatment always being the first treatment option). This was mitigated by the design and having a ‘management’ perspective which predicted and allowed for uptake of surgery in the non-surgical arm. The healthcare economic analysis had several limitations, including the sizeable amount of missing data on use of healthcare resources and EQ-5D-5L. We accounted for this using multiple imputation.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/14/140/63

Year Published: 2024

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/VDKB6009

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/VDKB6009

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