Surgery for knee articular cartilage injuries
| ISRCTN | ISRCTN90992837 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN90992837 |
| IRAS number | 270719 |
| Secondary identifying numbers | HTA - NIHR127849, IRAS 270719 |
- Submission date
- 05/03/2020
- Registration date
- 06/03/2020
- Last edited
- 18/01/2024
- Recruitment status
- Stopped
- Overall study status
- Stopped
- Condition category
- Musculoskeletal Diseases
Plain English Summary
Background and study aims
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 warrants surgical treatment. There are two main ways in which these injuries can be treated surgically, the first is to try to address the symptoms without trying to restore the cartilage; such as cleaning (debriding) the area or replacing the damaged area with an implant. 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 performed to encourage the cartilage to grow. A surgical tool is used to make perforations 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, termed Autologous Matrix-Induced Chondrogenesis (AMIC). 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 is 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. The study will find out whether adding the scaffold is worthwhile or not for patients with knee articular cartilage injuries.
Who can participate?
Patients aged 18 and over with a symptomatic chondral or osteochondral defect of the knee
What does the study involve?
Participants are randomly allocated into one of two groups. Those in the first group will have microfracture surgery with the insertion of a scaffold. Those in the second group will have microfracture surgery alone. Patients will be asked to attend the hospital for clinical follow-up at 3 months, 6 months, 1 year and 2 years after their surgery. The first three visits are part of routine care for patients following this surgery. The appointment at 2 years is outside of routine care and reasonable travel expenses will be covered. The researchers will ask patients to complete a questionnaire at baseline and then at each follow-up visit. This will provide information about the patient's general health and work status; for example, how they are feeling, what activities they are able to perform and how much pain they are feeling. Patients will also be asked some questions about any visits to hospital they have had, other healthcare they have received in the community, or any expenses and burdens they may have incurred because of their injury.
What are the possible benefits and risks of participating?
The researchers cannot promise that the study will help the participants, but it is hoped that the results from this study may help benefit the NHS and improve the management of future patients.
Where is the study run from?
North Bristol NHS Trust and the University of Bristol (UK)
When is the study starting and how long is it expected to run for?
September 2019 to October 2022
Who is funding the study?
National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme (UK)
Who is the main contact?
Michael Whitehouse (Chief Investigator) or Lucy Dabner (Trial Manager)
sismic-study@bristol.ac.uk
Contact information
Public
Level 7, Bristol Royal Infirmary
Upper Maudlin Street
Bristol
BS2 8HW
United Kingdom
 ORCID ID |
0000-0001-7269-1945 |
|---|---|
| Phone | +44 (0)117 342 2374 |
| sismic-study@bristol.ac.uk |
Scientific
Musculoskeletal Research Unit
University of Bristol, Level 1 Learning and Research Building, Southmead Hospital
Westbury-on-Trym
Bristol
BS10 5NB
United Kingdom
| ORCID ID |
0000-0003-2436-9024 |
|---|---|
| Phone | +44 (0)117 414 7843 |
| sismic-study@bristol.ac.uk |
Study information
| Study design | Multicentre parallel-group superiority randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific 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 |
| Study acronym | SISMIC |
| Study hypothesis | It is hypothesised that in patients with symptomatic chondral or osteochondral defects of the knee requiring treatment, microfracture with microstructural scaffold leads to a Knee Injury and Osteoarthritis Outcome Score superior outcome at 2-years compared with microfracture alone. The overall aim of this study is to evaluate the clinical and cost-effectiveness of microstructural scaffold in patients undergoing microfracture for a chondral or osteochondral defect of the knee. |
| Ethics approval(s) | Approved 15/06/2021, West Midlands - Black Country Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS; +44 (0)207 104 8010; blackcountry.rec@hra.nhs.uk), ref: 21/WM/0110 |
| Condition | Symptomatic chondral or osteochondral defect of the knee |
| Intervention | Randomisation will be performed using a secure internet-based randomisation system ensuring allocation concealment. Trial participants will be randomised in a 1:1 ratio to receive either microfracture of the chondral/osteochondral lesion with insertion of a bilayer collagen matrix microstructural scaffold or microfracture alone. Participants and clinical care teams (except for staff involved in the surgery) and members of the research team responsible for data collection will be blinded to allocation. Both groups will be followed for 2 years by clinical review to collect information about quality of life, symptoms and pain in the knee, complications of surgery, need for further surgery and costs to the NHS and patients. |
| Intervention type | Procedure/Surgery |
| Primary outcome measure | Articular cartilage repair outcome assessed using participant-reported Knee injury and Osteoarthritis Outcome Score (KOOS) collected using a questionnaire at baseline, 3, 6, 12 and 24 months |
| Secondary outcome measures | Data will be collected to characterise the following secondary outcomes over the 2-year follow up period: 1. Knee function assessed using International Knee Documentation Committee (IKDC) subjective knee evaluation score at 2 years (range 0-100 with 100 representing the best level of symptoms, function and activity). Domains include symptoms experienced over the last 1-4 weeks and when undertaking particular activities, including sporting activities and activities of daily living. It is reliable and validated with a minimal clinically important difference (MCID) of 9 points. This is collected using a questionnaire at baseline, 3, 6, 12 and 24 months. 2. Activity assessed using Tegner-Lysholm activity grading scale (range 0-100 with 100 representing the best level of function/activity). There are 8 questions based on ability or symptoms including limp, support, pain, instability, locking, swelling, stair-climbing and squatting. This is collected using a questionnaire at baseline, 3, 6, 12 and 24 months. 3. Health-related quality of life (HRQoL) assessed using EQ-5D-5L, a validated, generalised and standardised instrument comprising a visual analogue scale measuring self-rated health and a health status instrument of 5 domains related to daily activities. This instrument will be used to derived 2-year quality-adjusted life years (QALYs), by attaching UK preference-based utility indices to the EQ-5D-5L health states and weighting them with survival over time. This is collected using a questionnaire at baseline, 3, 6, 12 and 24 months. 4. Productivity assessed using Work Productivity and Activity Impairment (WPAI), a validated instrument which measures the impact of health and symptom severity on work productivity and non-work activities. Absenteeism and presenteeism will be valued using the human capital approach and estimates of average weekly earnings to estimate productivity losses for the economic evaluation. This is collected using a questionnaire at baseline, 3, 6, 12 and 24 months. 5. Complications, including bleeding, infection, deep vein thrombosis or pulmonary embolism, need for further surgery (non-joint replacement and joint replacement), collected on study case report forms by the research nurse. 6. Resources required to i) deliver the two treatments, ii) treat short- and long-term complications; iii) follow-up care in hospital, including rehabilitation, outpatient appointments, A&E, and re-admissions. Other health and social care resources required in the community and patient expenditures with their care will be collected from the participant using questionnaires at baseline, 3, 6, 12 and 24 months. Resources will be valued using Department of Health and Social Care reference costs, and national unit costs for health and social care, where available, or local sources otherwise. |
| Overall study start date | 01/09/2019 |
| Overall study end date | 25/10/2022 |
| Reason abandoned (if study stopped) | Lack of funding/sponsorship |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 176 |
| Total final enrolment | 10 |
| Participant inclusion criteria | 1. 18 years of age or older 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 3. Chondral or osteochondral lesion measuring no more than 4 cm2 |
| Participant exclusion criteria | Current participant exclusion criteria as of 12/08/2021: 1. Unstable, ligamentous injury to the knee that will not be treated 2. Unstable, meniscal tear that will not be treated 3. Less than 50% of native meniscal volume remaining in the knee following previous meniscal surgery 4. Knee alignment that in the opinion of the surgeon requires realignment surgery/osteotomy 5. Chondral or osteochondral lesion measuring >4 cm² following operative debridement of the lesion to a stable chondral rim 6. Chondral or osteochondral lesion that is being treated has been treated previously with one of the study interventions 7. Defects occurring on the tibial chondral surface 8. Patient unable/unwilling to adhere to trial procedures 9. Unable to provide written informed consent 10. Prisoners 11. Enrolled in another clinical trial and: 11.1. Co-enrolment is not permitted by the other trial 11.2. Co-enrolment would be burdensome for the patient 11.3. The intervention of the other trial could interfere with the SISMIC primary outcome Previous participant exclusion criteria: 1. Unstable, untreated ligamentous injury to the knee 2. Unstable, untreated meniscal tear 3. Less than 50% of native meniscal volume remaining in the knee following previous meniscal surgery 4. Knee alignment that in the opinion of the surgeon requires realignment surgery/osteotomy 5. Chondral or osteochondral lesion measuring >4 cm2 following operative debridement of the lesion to a stable chondral rim 6. The chondral or osteochondral lesion that is being treated has previously been treated with either of the study interventions 7. Defects occurring on the tibial chondral surface 8. Patient unable/unwilling to adhere to trial procedures 9. Unable to provide written informed consent 10. Prisoners 11. 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 |
| Recruitment start date | 28/10/2021 |
| Recruitment end date | 25/10/2022 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Southmead Road
Westbury-on-Trym
Bristol
BS10 5NB
United Kingdom
Sponsor information
Hospital/treatment centre
Research & Innovation
Level 3, Learning & Research building
Southmead Hospital, Westbury on Trym
Bristol
BS10 5NB
England
United Kingdom
| Phone | +44 (0)117 41 49336 |
|---|---|
| researchsponsor@nbt.nhs.uk | |
| Website | https://www.nbt.nhs.uk/research-innovation |
"ROR" |
https://ror.org/036x6gt55 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Health Technology Assessment Programme, HTA
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 15/06/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The findings will be disseminated by usual academic channels, i.e. presentation at international meetings, as well as by peer-reviewed publications (including a full report to the NIHR-HTA programme) and through patient organisations and newsletters to patients, where available. |
| IPD sharing plan | Data will not be made available for sharing until after publication of the main results of the study. Thereafter, anonymised individual patient data will be made available for secondary research, conditional on assurance from the secondary researcher that the proposed use of the data is compliant with the MRC Policy on Data Sharing regarding scientific quality, ethical requirements and value for money. A minimum requirement with respect to scientific quality will be a publicly available pre-specified protocol describing the purpose, methods and analysis of the secondary research, e.g. a protocol for a Cochrane systematic review. Please contact Michael Whitehouse using the following email: sismic-study@bristol.ac.uk. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol (other) | 19/01/2022 | No | No | ||
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
18/01/2024: The following changes were made to the study record:
1. The study was stopped as the funding was withdrawn before study completion.
2. The recruitment end date was changed from 01/01/2023 to 25/10/2022.
3. The overall trial end date was changed from 31/10/2026 to 25/10/2022.
4. The intention to publish date was changed from 31/10/2024 to 15/06/2024.
5. Total final enrolment and IRAS number added.
19/01/2022: The following changes were made to the trial record:
1. A link to the protocol was added.
2. The recruitment start date was changed from 01/09/2021 to 28/10/2021.
17/08/2021: The study contact has been updated.
13/08/2021: The study contact has been updated.
12/08/2021: The following changes have been made:
1. The recruitment start date has been changed from 01/02/2021 to 01/09/2021.
2. The recruitment end date has been changed from 01/04/2022 to 01/01/2023.
3. The overall trial end date has been changed from 31/10/2024 to 31/10/2026 and the plain English summary has been updated to reflect this change.
4. The ethics approval has been added.
5. The participant exclusion criteria have been updated.
01/12/2020: The recruitment start date was changed from 01/12/2020 to 01/02/2021.
15/10/2020: The recruitment start date was changed from 01/10/2020 to 01/12/2020.
28/07/2020: The recruitment start date was changed from 01/05/2020 to 01/10/2020.
05/03/2020: Trial's existence confirmed by the NIHR.
