Title: A Randomised Controlled Trial of Scaffold InSertion and MIcrofracture Compared to Microfracture Alone for the Treatment of Chondral or Osteochondral Defects of the Knee: The SISMIC Study
Funder: Department of Health and Social Care

Abstract: Knee injuries are common and can lead to pain and disability. Injuries to the smooth cartilage that lines the ends of the bone in joints can cause ongoing problems as the cartilage does not have a blood supply and rarely heals once injured. 10,000 people a year in the UK have a severe articular cartilage injury that needs surgical treatment. There are two main ways in which these injuries can be treated, the first is to try to address the symptoms without trying to restore the cartilage; such as cleaning (debriding) the area or replacing the joint. The other way is to try to repair or restore the cartilage in the damaged area. Cartilage does not grow back on its own, so an operation known as “microfracture” can be done to encourage the cartilage to grow. A surgical tool is used to make regular holes in the bone in the damaged area which allows blood and bone marrow to seep out of the holes, encouraging healing. A “scaffold”, which is usually made of the same material that makes up most of the cartilage (collagen), can be added to microfracture. The scaffold is secured in place and acts as a template for new cartilage to form on. It is not clear if using a scaffold improves the outcome for patients. Using scaffold makes the operation more complex (approximately 20 minutes longer) and the cost of the scaffold adds approximately £900, so it is important to establish if adding a scaffold results in a better outcome for patients and is cost-effective for the NHS._x000D_ _x000D_ The study will find out whether adding the scaffold is worthwhile or not for patients with these injuries. Over 2 years we will aim to recruit 176 patients from at least 11 hospitals, who will be divided into two equal sized groups. One group will have microfracture plus scaffold and the other will have microfracture alone. Everything else will be the same for all patients. The groups will be chosen by a process called randomisation to ensure that groups have similar patients in terms of general health, age, sex etc. This allows a fair comparison to be made between the two groups. Both groups will be followed for 2 years by clinical review and questionnaire and information about quality of life, the symptoms and pain in the knee, complications of surgery, need for further surgery and costs to the NHS and patients will be collected. _x000D_ _x000D_ The number of patients agreeing to take part and being followed up successfully will be checked in each hospital and, after 10 months, the information will be reviewed to make sure that it is possible to complete a full trial._x000D_ _x000D_ This study will be carried out by an experienced multi-disciplinary team of surgeons, researchers and patient representatives with experience of musculoskeletal health conditions, who will have input to all stages of the project, from the design of patient materials to dissemination of results. We expect it will take just over 5 years. An independent group of surgeons, researchers and lay members/patients will review the study regularly and provide advice. The results will be made publicly available to inform future care of patients with this kind of knee injury.

Lay abstract: BACKGROUND: Up to 10,000 patients a year suffer from knee articular cartilage injuries warranting repair, most of whom are under 35 years of age. Treatment focuses on restoring cartilage by methods such as microfracture which involves penetrating bone in the area to release fibrin and stem cells. It has been suggested that results may be better if a scaffold is also used to help the repair._x000D_ _x000D_ AIM: To compare the clinical and cost effectiveness of microstructural scaffold insertion with microfracture versus microfracture alone for the treatment of chondral or osteochondral knee defects._x000D_ _x000D_ DESIGN: Multicentre, parallel group, randomised superiority trial with blinding of participants and clinical staff not involved in the surgery, an internal pilot phase to determine the feasibility of recruitment and adherence to the protocol, active follow-up to 2 years and longer-term follow-up using routine data._x000D_ _x000D_ SETTING: Secondary and tertiary care NHS hospitals._x000D_ _x000D_ POPULATION: Adults (aged 18 years and over) with symptoms arising from a chondral or osteochondral defect of the knee._x000D_ _x000D_ INCLUSION CRITERIA:_x000D_ 1. 18 years of age or older_x000D_ 2. Symptomatic chondral or osteochondral defect of the knee sited on the medial or lateral femoral condyles, trochlea or patella as confirmed by standard clinical practice._x000D_ 3. Chondral or osteochondral lesion measuring no more than 4cm2 _x000D_ _x000D_ _x000D_ EXCLUSION CRITERIA: _x000D_ 1. Unstable, ligamentous injury to the knee that will not be treated_x000D_ 2. Unstable, meniscal tear that will not be treated_x000D_ 3. Less than 50% of native meniscal volume remaining in the knee following previous meniscal surgery_x000D_ 4. Knee alignment that in the opinion of the surgeon requires realignment surgery/osteotomy_x000D_ 5. Chondral or osteochondral lesion measuring >4cm2 following operative debridement of the lesion to a stable chondral rim_x000D_ 6. Chondral or osteochondral lesion has been treated previously with one of the study interventions. _x000D_ 7. Defects occurring on the tibial chondral surface_x000D_ 8. Patient unable/unwilling to adhere to trial procedures_x000D_ 9. Unable to provide informed consent_x000D_ 10. Enrolled in another clinical trial and: a) co-enrolment is not permitted by the other trial; or b) co-enrolment would be burdensome for the patient; c) the intervention of the other trial could interfere with the SISMIC primary outcome._x000D_ _x000D_ INTERVENTIONS: Experimental: microfracture of the chondral/osteochondral lesion with insertion of a bilayer collagen matrix microstructural scaffold. Control: microfracture alone._x000D_ _x000D_ OUTCOME MEASURES: Primary: Knee injury and Osteoarthritis Outcome Score (KOOS), a validated score for articular cartilage repair at 2-years; Secondary: Knee function: International Knee Documentation Committee (IKDC) subjective knee evaluation score; Activity: Tegner-Lysholm activity grading scale; Quality of life: EQ-5D-5L; Productivity: Work Productivity and Activity Impairment scale; Postoperative complications (e.g. infection, venous thrombosis, further surgery); Resource use._x000D_ _x000D_ SAMPLE SIZE: The MCID for the KOOS at 2 years is 10 points and the standard deviation (SD) is approximately 18. A sample size of 176 participants (88/group) will provide 90% power to detect an effect size of 0.56 SD with 5% statistical significance (two-tailed), allowing for 20% loss to follow-up._x000D_ _x000D_ ANALYSIS: The effectiveness analyses will follow a pre-specified analysis plan. The primary analyses will be by intention to treat. Trial results will be reported in line with the CONSORT guidelines. The within-trial economic evaluation will be conducted from an NHS and personal social services perspective at 2 years, following NICE guidelines._x000D_ _x000D_ PROJECT TIMETABLE INCLUDING RECRUITMENT RATE: The study will aim to recruit an average 1 patient/centre/month. Study duration 62 m: 8 m set up, 24 m recruitment (8 m internal pilot, 16 m main trial), 24 m follow-up on all participants; 6 m analysis and report. Longer term outcomes to 5 and 10 years will be assessed using routine data (subject to further funding)._x000D_ _x000D_ ANTICIPATED IMPACT & DISSEMINATION: Results will be presented and published in peer-reviewed journals and made available to patients, the public and other stakeholders through a variety of media. Scaffolds are used in approximately 20% of eligible patients in the sites we have approached for SISMIC. If the microfracture and scaffold is shown to be superior to microfracture alone, the proportion of patients treated with scaffolds would increase substantially, whereas if no benefit is shown, the significant time and resource being used currently would be reduced.

Research activity codes: 6.4 SURGERY
Health categories: MUSCULOSKELETAL