The Role of Synovectomy in Pain Reduction Following Total Knee Arthroplasty

Study Overview
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Brief Summary
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Osteoarthritis (OA) is the most common joint disease, causing severe pain due to joint inflammation (synovitis). While total knee arthroplasty (TKA) is commonly performed to reduce pain, 20% of patients are dissatisfied with their outcome post-surgery. This dissatisfaction is caused by persistent pain post-TKA due to synovitis that is not routinely removed during surgery. To address this problem, a synovectomy can be performed during TKA, which involves resecting the inflamed layer of tissue lining the joint, called the synovium, and its associated sensory nerve endings. Since the synovium will regenerate in the months post-surgery, synovectomy only transiently reduces pain after TKA. The proposed study will help ascertain the benefits and effects of synovectomy in patients who are more likely to experience poor satisfaction (driven mostly by pain) post-TKA. This study will include 62 patients undergoing TKA due to end-stage OA who have moderate to severe synovitis, as determined by ultrasound assessment. Patients will be randomized (1:1) to undergo a TKA with synovectomy or without synovectomy. Primary and secondary outcomes will be assessed through patient-reported levels of pain and function, results from physical performance tests, and quality of life (QOL) scores. These measures will be recorded pre- and post-surgery for comparison. Through demonstrating that synovectomy can at least transiently reduce pain post-TKA, this study will provide evidence for the development of medical therapies that target the synovium to slow its regrowth. This will be transformative for the long-term management of joint pain and synovitis post-surgery, thus significantly improving patients' overall QOL.

Official Title
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The Role of Synovectomy in Pain Reduction Among Osteoarthritis Patients Following Total Knee Arthroplasty

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Procedure: Synovectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females over the age of 40 diagnosed with knee osteoarthritis Scheduled for first unilateral total knee arthroplasty Moderate to severe (at least grade two) synovitis and synovial hyperplasia, as determined by ultrasound assessment Referred to the Pre-Admission Clinic at University Hospital Exclusion Criteria: Bilateral, second, uni-compartmental, or revision total knee arthroplasty Osteoarthritis due to genetic syndromes (e.g., Ehlers-Danlos Syndrome, etc.) Known inflammatory arthropathy, another rheumatic disease, or disease-modifying anti-rheumatic drug (DMARD) use (e.g. methotrexate, hydroxychloroquine, sulfasalazine, leflunomide, TNF inhibitors, etc.) - note: Gout is NOT an exclusion Cannot read, write, or understand English (printed instructions are provided in English only) Any factors precluding patients from attending follow-up appointments (e.g., socio-economic limitations, distance from clinic, no access to home/cell phone, etc.). Cognitive impairment or psychological problems that preclude the ability to understand instructions Not able to follow up at routine standard of care post-operative visits Joint injection (steroid or viscosupplement) within 12 weeks of Pre-admission Clinic visit date

Ages Eligible for Study
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Minimum Age: 41 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Total knee replacement with synovectomy<br>Patients in this arm will undergo synovectomy during total knee replacement surgery. | Procedure: Synovectomy<br>* Patients in the intervention group will undergo synovectomy during total knee replacement surgery<br>|
| No Intervention: Total knee replacement without synovectomy<br>Patients in this arm will not undergo synovectomy during total knee replacement surgery. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients' self-reported level of pain | Pain will be measured using the pain sub-scale (nine items) of the Knee injury and Osteoarthritis Outcome Score (KOOS). Each question on the KOOS is a self-administered questionnaire is assigned a score from zero (no problems) to four (extreme problems) using a five-point Likert scale. The average of each sub-scale is calculated independently. Sub-scale scores range from zero (minimum), indicating severe knee problems, to 100 (maximum), indicating no knee problems (therefore, a higher score is better). The KOOS has demonstrated face validity and construct validity, as well as excellent test-retest reliability for each domain. It has also shown to be responsive to change in patients with knee OA. | 12 weeks post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Joint function - 30-Second Sit to Stand Test | The 30-Second Sit to Stand Test, which assesses leg strength and endurance in older adults, requires patients to complete as many full stands from the chair as possible in a 30-second time period. The number of full stands completed is compared to values that correspond to the patient's age group to determine their level of performance (a higher number is better). | 6, 12, 18, and 24 weeks post-surgery | 
| Joint function - Timed Up and Go Test | To begin the Timed Up and Go Test, patients will be seated in a chair. They will be signalled to stand up, walk to a line positioned three meters away from the chair, and walk back at a normal pace. Patients will then be instructed to return to their seated position. Patients' time, in seconds, will be recorded. Taking a longer time to perform this test indicates that the patient is less mobile, has a poorer sense of balance, and is at a higher risk of falling (taking a longer time is worse). | 6, 12, 18, and 24 weeks post-surgery | 
| Patients' self-reported quality of life | Quality of life will be evaluated using the European Quality of Life Five-Dimension (EQ-5D). The EQ-5D measures generic quality of life and consists of domains concluding mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Scores range from zero to one, with higher scores indicating a better quality of life. This tool has strong test re-test reliability and cross-sectional construct validity in patients with knee OA. | 6, 12, 18, and 24 weeks post-surgery | 
| Symptoms sub-scale of the Knee injury and Osteoarthritis Outcome Score (KOOS) | This sub-scale contains seven items. Each question on the KOOS self-administered questionnaire is assigned a score from zero (no problems) to four (extreme problems) using a five-point Likert scale. The average of each sub-scale is calculated independently. Sub-scale scores range from zero (minimum), indicating severe knee problems, to 100 (maximum), indicating no knee problems (therefore, a higher score is better). The KOOS has demonstrated face validity and construct validity, as well as excellent test-retest reliability for each domain. It has also shown to be responsive to change in patients with knee OA. | 6, 12, 18, and 24 weeks post-surgery | 
| Activities of daily living sub-scale of the Knee injury and Osteoarthritis Outcome Score (KOOS) | This sub-scale contains 17 items. Each question on the KOOS self-administered questionnaire is assigned a score from zero (no problems) to four (extreme problems) using a five-point Likert scale. The average of each sub-scale is calculated independently. Sub-scale scores range from zero (minimum), indicating severe knee problems, to 100 (maximum), indicating no knee problems (therefore, a higher score is better). The KOOS has demonstrated face validity and construct validity, as well as excellent test-retest reliability for each domain. It has also shown to be responsive to change in patients with knee OA. | 6, 12, 18, and 24 weeks post-surgery | 
| Knee-related quality of life sub-scale of the Knee injury and Osteoarthritis Outcome Score (KOOS) | This sub-scale contains four items. Each question on the KOOS self-administered questionnaire is assigned a score from zero (no problems) to four (extreme problems) using a five-point Likert scale. The average of each sub-scale is calculated independently. Sub-scale scores range from zero (minimum), indicating severe knee problems, to 100 (maximum), indicating no knee problems (therefore, a higher score is better). The KOOS has demonstrated face validity and construct validity, as well as excellent test-retest reliability for each domain. It has also shown to be responsive to change in patients with knee OA. | 6, 12, 18, and 24 weeks post-surgery |