A Randomized, Study to Evaluate the Iovera° Device in Treating Pain Associated With Total Knee Arthroplasty

Study Overview
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Brief Summary
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This study will evaluate the iovera° device in treating pain associated with total knee arthroplasty (TKA). This study will also assess if overall pain medication is reduced following TKA and will investigate the relationship between patients treated with the iovera° device and length of hospital stay, pain, patient satisfaction and improved rehabilitation.

Official Title
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A Post-Market, Multi-Center, Prospective, Double-Blind, Randomized, Controlled Study to Evaluate the Iovera° Device in Treating Pain Associated With Total Knee Arthroplasty

Conditions
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Arthritis of the Knee

Intervention / Treatment
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* Device: iovera°
* Device: iovera° Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 22 to 79 years of age Scheduled to undergo primary unilateral TKA under spinal anesthesia for primary diagnosis of osteoarthritis American Society of Anesthesiology (ASA) Physical Classification System classes I-III Anticipation of discharge to home after inpatient acute post-op phase (age, co-morbidities, home environment, and social support are in favor of discharge to home in the opinion of the Investigator) Subject is willing and able to give written informed consent. Subject is fluent in verbal and written English. Subject is willing and able to comply with study instructions and commit to all follow-up visits for the duration of the study. Subject is in good general health and free of any systemic disease state or physical condition that might impair evaluation or which in the Investigator's opinion, exposes the Subject to an unacceptable risk by study participation. Exclusion Criteria:Exclusion Criteria Chronic opioid use (defined as daily or almost daily use of opioids for >3 months). Concurrent painful physical condition, surgery, or musculoskeletal disease that requires or may require analgesic treatment during study follow-up that is not strictly related to the target knee being treated with iovera°, which have the potential to confound the postoperative assessments (e.g., significant pain from other joints, chronic neuropathic pain, concurrent or planned contralateral TKA, concurrent foot, neck, spine, hip, or other musculoskeletal disease, arthritis, or planned surgery, etc.). Greater than 15° malalignment (varus or valgus) on pre-operative radiograph. Previous myoscience FCT™ treatment. Previous Partial or Total Knee Arthroplasty. Partial or Total Knee Arthroplasty of the contralateral knee is permitted if [surgery was completed at least twelve (12) months prior to screening]. Body Mass Index ≥ 40 Prior surgery in the treatment areas that may alter the anatomy of the infrapatellar branch of the saphenous nerve (ISN) or the anterior femoral cutaneous nerve (AFCN) or result in scar tissue in the treatment area. Any clotting disorder and/or use of an anticoagulant (e.g. warfarin, clopidogrel, etc.) within seven (7) days prior to administration of the device. Low dose aspirin (81mg or less daily) for cardiac prophylaxis allowed. Any local skin condition at the treatment sites that in the Investigator's opinion would adversely affect treatment or outcomes. Open and/or infected wound in the treatment areas. Allergy to lidocaine. History of cryoglobulinemia History of paroxysmal cold hemoglobinuria. History of cold urticaria. History of Raynaud's disease. History of opioid or alcohol abuse. Subject is pregnant or planning to become pregnant while enrolled in the study. Current enrollment in any investigational drug or device study or participation within 30 days prior to screening. Currently being treated for related knee injury under worker's compensation claim or equivalent (i.e. legal case). Any chronic medical condition that in the Investigator's opinion would prevent adequate participation. Any chronic medication use (prescription, over-the-counter, etc.) that in the Investigator's opinion would affect study participation or Subject safety. For any reason, in the opinion of the Investigator, the Subject may not be a suitable candidate for study participation (i.e., history of noncompliance, drug dependency, etc.).

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Treatment with focused cold therapy. | Device: iovera°<br>* Use of iovera° device to administer treatment Focused Cold Therapy<br>|
| Sham Comparator: Sham<br>Sham treatment with focused cold therapy device | Device: iovera° Sham<br>* iovera° device used for sham treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative Consumption of Opioids Total Daily Morphine Equivalent (TME) (mg/Day) | The cumulative morphine equivalent was divided by the number of days to provide a Total Daily Morphine Equivalent (TME) for each Subject. | hospital discharge to 6 Weeks post-TKA surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pain From Baseline to Six Weeks | The Numeric Rating Scale for Pain (NRS for Pain) is a measure of pain intensity which is assessed on a scale from 0 to 10 with 0 being no pain at all and 10 being the worst pain imaginable. The Subject provides a self-reported score based on their pain in the target knee at the time the questionnaire is administered (labeled 'now' in the tables below) as well as their pain in the past 7 days (labeled past 7 in the tables below). | Baseline to 6 Weeks | 
| Change in WOMAC Scores at 6 Weeks After Surgery | The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is a tri-dimensional, disease-specific, Subject-reported outcome measure. It consists of 24 questions with 5 questions regarding pain, 2 questions regarding stiffness and 17 questions regarding function in Subjects with osteoarthritis of the hip and/or knee. Each question is answered on a scale of 0 (none)-10 (extreme). Higher scores are associated with worse outcomes. | Baseline to 6 weeks after surgery | 
| Length of Hospital Stay |  | treatment to hospital discharge | 
| Change in Active Range of Motion From Baseline to 2 Weeks After Surgery | Range of motion measures the physical function of the replaced knee during active flexion at the specified timepoints. | baseline to 2 weeks after surgery | 
| 40 Meter Walk Test | The 40 Meter Walk Test measured the average speed in meters per second a Subject could walk 40 meters. | Baseline, 2,4,6,12 weeks | 
| 30 Second Chair Test | The 30 Second Chair Test evaluates physical function during recovery by measuring the number of times a subject could go from seated in a chair to standing over the course of 30 seconds. | Baseline, 2,4,6,12 weeks after surgery | 
| Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | The 36-question survey captures the Subject's perception of their general health by sorting them into multi-item scales that assess eight health concepts rather than a single total score. The survey used ten components to assess the health concepts: Physical, Mental, Physical Functioning, Role- Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Health Transition. Subject responses to the SF-36 survey were recorded. Scores can range from 0 to 100. Higher scores indicate better health status, and a mean score of 50 has been articulated as a normative value for all scales. | Baseline to Week 6 | 
| Change in Patient Reported Outcomes Measurement Information System (PROMIS) From Baseline to Week 6 | 8 domains assessing physical, mental and social health while also covering important areas of self-reported health: pain, fatigue, depression, anxiety, sleep, and physical function. A high PROMIS domain sub-score indicates more of that concept being measured. PROMIS scores have a mean of 50 and standard deviation (SD) of 10 in a referent population. The referent population is usually the US General Population. lower scores are less favorable, and higher scores are more favorable. | Baseline to 6 weeks after surgery |