Arthritis of the Knee
Conditions
Brief summary
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.
Interventions
DEVICEiovera°
Use of iovera° device to administer treatment Focused Cold Therapy
DEVICEiovera° Sham
iovera° device used for sham treatment
Sponsors
Pacira Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
22 Years to 79 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Consumption of Opioids Total Daily Morphine Equivalent (TME) (mg/Day) | hospital discharge to 6 Weeks post-TKA surgery | The cumulative morphine equivalent was divided by the number of days to provide a Total Daily Morphine Equivalent (TME) for each Subject. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in WOMAC Scores at 6 Weeks After Surgery | Baseline to 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. |
| Length of Hospital Stay | treatment to hospital discharge | — |
| Change in Active Range of Motion From Baseline to 2 Weeks After Surgery | baseline to 2 weeks after surgery | Range of motion measures the physical function of the replaced knee during active flexion at the specified timepoints. |
| Change in Pain From Baseline to Six Weeks | Baseline to 6 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). |
| 30 Second Chair Test | Baseline, 2,4,6,12 weeks after surgery | 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. |
| Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | Baseline to Week 6 | 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. |
| Change in Patient Reported Outcomes Measurement Information System (PROMIS) From Baseline to Week 6 | Baseline to 6 weeks after surgery | 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. |
| 40 Meter Walk Test | Baseline, 2,4,6,12 weeks | The 40 Meter Walk Test measured the average speed in meters per second a Subject could walk 40 meters. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Treatment with focused cold therapy.
iovera°: Use of iovera° device to administer treatment Focused Cold Therapy | 74 |
| Sham Sham treatment with focused cold therapy device
iovera° Sham: iovera° device used for sham treatment | 76 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | non-compliance | 0 | 1 |
| Overall Study | not provided | 0 | 1 |
| Overall Study | surgery cancelled | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Treatment | Sham | Total |
|---|---|---|---|
| Age, Continuous | 65.3 years STANDARD_DEVIATION 7.53 | 65.3 years STANDARD_DEVIATION 9.33 | 65.3 years STANDARD_DEVIATION 8.46 |
| BMI | 31.0 kg/m^2 STANDARD_DEVIATION 4.61 | 30.6 kg/m^2 STANDARD_DEVIATION 4.79 | 30.79 kg/m^2 STANDARD_DEVIATION 4.69 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 14 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 58 Participants | 60 Participants | 118 Participants |
| Region of Enrollment United States | 74 participants | 76 participants | 150 participants |
| Sex: Female, Male Female | 38 Participants | 45 Participants | 83 Participants |
| Sex: Female, Male Male | 36 Participants | 31 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 74 | 0 / 76 |
| other Total, other adverse events | 24 / 74 | 24 / 76 |
| serious Total, serious adverse events | 5 / 74 | 5 / 76 |
Outcome results
Primary
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.
Time frame: hospital discharge to 6 Weeks post-TKA surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Cumulative Consumption of Opioids Total Daily Morphine Equivalent (TME) (mg/Day) | 23.9 mg/day | Standard Deviation 15.25 |
| Sham | Cumulative Consumption of Opioids Total Daily Morphine Equivalent (TME) (mg/Day) | 27.1 mg/day | Standard Deviation 20.87 |
Secondary
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.
Time frame: Baseline, 2,4,6,12 weeks after surgery
Population: The variation in number analyzed is due to the actual number of participants with data collected at specific timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | 30 Second Chair Test | 12 weeks | 12.1 number of repetitions | Standard Deviation 4.31 |
| Treatment | 30 Second Chair Test | Baseline | 8.2 number of repetitions | Standard Deviation 3.38 |
| Treatment | 30 Second Chair Test | 2 weeks | 6.9 number of repetitions | Standard Deviation 3.26 |
| Treatment | 30 Second Chair Test | 4 weeks | 9.6 number of repetitions | Standard Deviation 3.81 |
| Treatment | 30 Second Chair Test | 6 weeks | 12.4 number of repetitions | Standard Deviation 13.75 |
| Sham | 30 Second Chair Test | 6 weeks | 11.1 number of repetitions | Standard Deviation 3.93 |
| Sham | 30 Second Chair Test | 4 weeks | 9.5 number of repetitions | Standard Deviation 3.81 |
| Sham | 30 Second Chair Test | Baseline | 8.6 number of repetitions | Standard Deviation 4.34 |
| Sham | 30 Second Chair Test | 12 weeks | 13.0 number of repetitions | Standard Deviation 4.11 |
| Sham | 30 Second Chair Test | 2 weeks | 7.5 number of repetitions | Standard Deviation 3.07 |
Secondary
40 Meter Walk Test
The 40 Meter Walk Test measured the average speed in meters per second a Subject could walk 40 meters.
Time frame: Baseline, 2,4,6,12 weeks
Population: The variation in number analyzed is due to the actual number of participants with data collected at specific timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | 40 Meter Walk Test | 2 weeks | 0.8 meters per second | Standard Deviation 0.34 |
| Treatment | 40 Meter Walk Test | 4 weeks | 0.9 meters per second | Standard Deviation 0.31 |
| Treatment | 40 Meter Walk Test | 6 weeks | 1.0 meters per second | Standard Deviation 0.34 |
| Treatment | 40 Meter Walk Test | 12 weeks | 1.1 meters per second | Standard Deviation 0.35 |
| Treatment | 40 Meter Walk Test | Baseline | 1 meters per second | Standard Deviation 0.41 |
| Sham | 40 Meter Walk Test | Baseline | 1 meters per second | Standard Deviation 0.42 |
| Sham | 40 Meter Walk Test | 12 weeks | 1.1 meters per second | Standard Deviation 0.36 |
| Sham | 40 Meter Walk Test | 4 weeks | 0.9 meters per second | Standard Deviation 0.34 |
| Sham | 40 Meter Walk Test | 2 weeks | 0.8 meters per second | Standard Deviation 0.31 |
| Sham | 40 Meter Walk Test | 6 weeks | 1.0 meters per second | Standard Deviation 0.38 |
Secondary
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.
Time frame: Baseline to Week 6
Population: The variation in number analyzed is due to the actual number of participants with data collected at specific timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | Physical Component | 3.8 change in score on a scale | Standard Deviation 7.7 |
| Treatment | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | Mental Component | 0.7 change in score on a scale | Standard Deviation 10.73 |
| Treatment | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | Physical Functioning | 13.6 change in score on a scale | Standard Deviation 23.83 |
| Treatment | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | Role-Physical Component | 4.3 change in score on a scale | Standard Deviation 31.83 |
| Treatment | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | Bodily Pain Component | 13.2 change in score on a scale | Standard Deviation 23.07 |
| Treatment | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | General Health Component | 1.7 change in score on a scale | Standard Deviation 12.18 |
| Treatment | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | Vitality Component | 3.2 change in score on a scale | Standard Deviation 20.15 |
| Treatment | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | Social Functioning Component | 4.3 change in score on a scale | Standard Deviation 30.56 |
| Treatment | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | Role Emotional | 0.7 change in score on a scale | Standard Deviation 32.61 |
| Treatment | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | Health Transition Component | -0.5 change in score on a scale | Standard Deviation 1.13 |
| Sham | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | Social Functioning Component | 4.5 change in score on a scale | Standard Deviation 27.54 |
| Sham | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | Physical Component | 6.3 change in score on a scale | Standard Deviation 9.58 |
| Sham | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | General Health Component | 1.5 change in score on a scale | Standard Deviation 14.17 |
| Sham | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | Mental Component | 0.3 change in score on a scale | Standard Deviation 10.61 |
| Sham | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | Health Transition Component | -0.07 change in score on a scale | Standard Deviation 1.12 |
| Sham | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | Physical Functioning | 16.7 change in score on a scale | Standard Deviation 28.49 |
| Sham | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | Vitality Component | 4.2 change in score on a scale | Standard Deviation 17.78 |
| Sham | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | Role-Physical Component | 17.8 change in score on a scale | Standard Deviation 33.67 |
| Sham | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | Role Emotional | 7.4 change in score on a scale | Standard Deviation 34.62 |
| Sham | Change 36-Item Short Form Health Survey (SF-36) From Baseline to 6 Weeks | Bodily Pain Component | 16.9 change in score on a scale | Standard Deviation 26.66 |
Secondary
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.
Time frame: baseline to 2 weeks after surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in Active Range of Motion From Baseline to 2 Weeks After Surgery | -10.1 Degrees | Standard Deviation 19.51 |
| Sham | Change in Active Range of Motion From Baseline to 2 Weeks After Surgery | -11.8 Degrees | Standard Deviation 15.56 |
Secondary
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).
Time frame: Baseline to 6 Weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Change in Pain From Baseline to Six Weeks | Now | -2.7 score on a scale | Standard Deviation 2.96 |
| Treatment | Change in Pain From Baseline to Six Weeks | Past 7 days | -2.4 score on a scale | Standard Deviation 3.01 |
| Sham | Change in Pain From Baseline to Six Weeks | Now | -3.6 score on a scale | Standard Deviation 3.03 |
| Sham | Change in Pain From Baseline to Six Weeks | Past 7 days | -2.9 score on a scale | Standard Deviation 3.28 |
Secondary
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.
Time frame: Baseline to 6 weeks after surgery
Population: The variation in number analyzed is due to the actual number of participants with data collected at specific timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Change in Patient Reported Outcomes Measurement Information System (PROMIS) From Baseline to Week 6 | Physical Function | -2.3 score on a scale | Standard Deviation 4.36 |
| Treatment | Change in Patient Reported Outcomes Measurement Information System (PROMIS) From Baseline to Week 6 | Sleep Disturbance | 0.1 score on a scale | Standard Deviation 1.83 |
| Treatment | Change in Patient Reported Outcomes Measurement Information System (PROMIS) From Baseline to Week 6 | Depression | -0.3 score on a scale | Standard Deviation 2.47 |
| Treatment | Change in Patient Reported Outcomes Measurement Information System (PROMIS) From Baseline to Week 6 | Ability to Participate in Social Roles and Activities | -0.3 score on a scale | Standard Deviation 4.48 |
| Treatment | Change in Patient Reported Outcomes Measurement Information System (PROMIS) From Baseline to Week 6 | Anxiety | -1.0 score on a scale | Standard Deviation 3.17 |
| Treatment | Change in Patient Reported Outcomes Measurement Information System (PROMIS) From Baseline to Week 6 | Fatigue | 9.6 score on a scale | Standard Deviation 3.74 |
| Treatment | Change in Patient Reported Outcomes Measurement Information System (PROMIS) From Baseline to Week 6 | Pain Intensity | -2.6 score on a scale | Standard Deviation 2.8 |
| Treatment | Change in Patient Reported Outcomes Measurement Information System (PROMIS) From Baseline to Week 6 | Pain Interference | -2.5 score on a scale | Standard Deviation 4.55 |
| Sham | Change in Patient Reported Outcomes Measurement Information System (PROMIS) From Baseline to Week 6 | Pain Intensity | -3.3 score on a scale | Standard Deviation 2.8 |
| Sham | Change in Patient Reported Outcomes Measurement Information System (PROMIS) From Baseline to Week 6 | Physical Function | -2.6 score on a scale | Standard Deviation 4.5 |
| Sham | Change in Patient Reported Outcomes Measurement Information System (PROMIS) From Baseline to Week 6 | Anxiety | -1.2 score on a scale | Standard Deviation 2.94 |
| Sham | Change in Patient Reported Outcomes Measurement Information System (PROMIS) From Baseline to Week 6 | Depression | 0.1 score on a scale | Standard Deviation 2.85 |
| Sham | Change in Patient Reported Outcomes Measurement Information System (PROMIS) From Baseline to Week 6 | Fatigue | 8.7 score on a scale | Standard Deviation 3.79 |
| Sham | Change in Patient Reported Outcomes Measurement Information System (PROMIS) From Baseline to Week 6 | Sleep Disturbance | 0.22 score on a scale | Standard Deviation 1.98 |
| Sham | Change in Patient Reported Outcomes Measurement Information System (PROMIS) From Baseline to Week 6 | Ability to Participate in Social Roles and Activities | -0.6 score on a scale | Standard Deviation 3.83 |
| Sham | Change in Patient Reported Outcomes Measurement Information System (PROMIS) From Baseline to Week 6 | Pain Interference | -2.8 score on a scale | Standard Deviation 4.56 |
Secondary
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.
Time frame: Baseline to 6 weeks after surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Change in WOMAC Scores at 6 Weeks After Surgery | Pain | -13.1 score on a scale | Standard Deviation 12.6 |
| Treatment | Change in WOMAC Scores at 6 Weeks After Surgery | Stiffness | -4.7 score on a scale | Standard Deviation 5.29 |
| Treatment | Change in WOMAC Scores at 6 Weeks After Surgery | Physical Function | -49.4 score on a scale | Standard Deviation 41.66 |
| Sham | Change in WOMAC Scores at 6 Weeks After Surgery | Pain | -14.6 score on a scale | Standard Deviation 13.18 |
| Sham | Change in WOMAC Scores at 6 Weeks After Surgery | Stiffness | -5.5 score on a scale | Standard Deviation 6.78 |
| Sham | Change in WOMAC Scores at 6 Weeks After Surgery | Physical Function | -51.4 score on a scale | Standard Deviation 44.56 |
Secondary
Length of Hospital Stay
Time frame: treatment to hospital discharge
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Length of Hospital Stay | 54.7 Hours | Standard Deviation 27.34 |
| Sham | Length of Hospital Stay | 52.6 Hours | Standard Deviation 24.42 |