Degeneration; Articular Cartilage, Knee, Osteoarthritis, Knee, Rheumatoid Arthritis
Conditions
Keywords
total knee replacement, rehabilitation, exercise program, total knee arthroplasty
Brief summary
Although total knee replacement (TKR) improves pain in numerous patients, it does not resolve many of the substantial functional limitations and physical inactivity that existed for a long time prior to the surgery. Exercise is an intervention that could improve these long-term limitations. To promote these improvements, exercise should be implemented at later stage post TKR when patients can tolerate doses of exercise sufficiently high to promote substantial changes. To date, we just don't have enough good research to tell us which type of exercise works best for which patients and under which circumstances at later stage post TKR. This research study will provide evidence for recommended interventions during the later stage post TKR. The specific research questions are: (1) How do group exercise in the community and individual exercise in rehabilitation clinic compare with usual medical care on physical function and activity outcomes? (2) Who are the patients most likely to respond to each exercise intervention? (3) Are the approaches safe?
Detailed description
This is a comparative effectiveness study, designed as a 3-group single-blind randomized clinical trial. Two hundred forty older adults who underwent TKR at least 2 months prior and are otherwise eligible will be randomized into one of three treatment approaches: 1) clinic-based individual outpatient rehabilitative exercise; 2) community-based group exercise classes; or 3) usual medical care. Subjects will be treated for 3 months. Data will be collected before intervention, after intervention (3 months), and 6 months after randomization. Physical function is a primary outcome and will be assessed by the Western Ontario and McMaster Universities Arthritis Index and a battery of performance-based tests germane to patients post TKR that includes ability to walk, manage stairs, lift from the floor and the chair, and one-leg balance. We will also use an accelerometer-based monitor that provides a real-time measure of physical activity during normal daily living and is able to accurately capture most levels of activity. Linear mixed models will be fitted to compare the changes in outcome across groups. Logistic regression will identify patient characteristics that predict functional recovery in the exercise groups. Survival analysis and instrumental variable methods will be used to compare attrition, adherence and adverse events between groups.
Interventions
OTHERClinic-based outpatient exercise group
Subjects will participate in supervised sessions (clinic-based) of exercise followed by a home exercise program 2 times per week during 3 months. Each exercise session will last about 60 minutes. Treatment sessions will utilize a pragmatic approach and will include the exercises designed to increase muscular strength, low impact cardiovascular exercise, range of movement, and activity for daily living skills.
OTHERCommunity-based exercise group
Subjects will attend to exercise classes (community-based) 2 times per week during 3 months. The exercise classes last approximately 60 minutes. The group exercise classes consists of a variety of exercises designed to increase general muscular strength, low impact aerobic exercise, range of movement, and activity for daily living.
Sponsors
Patient-Centered Outcomes Research Institute
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Unilateral TKR 2 to 4 months prior * Older than 60 years of age * Experience functional limitation in daily activities (score in WOMAC-PF of at least 9 points) * Speak sufficient English to understand study instructions * Have medical clearance to participate in the study * Are willing to be randomized to one of the 3 treatment arms
Exclusion criteria
* Have absolute or relative contraindications to exercise * Have history of uncontrolled cardiovascular disease or hypertension * Are unable to walk 50 meters without an assistive device * Have history of muscular or neurological disorder that affect lower extremity function * Regular participation in exercise * Terminal illness * Planning to have another joint replacement during the next 12 months * Plan not to be around during the next 12 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Western Ontario and McMaster Universities Osteoarthritis Index Physical Function (WOMAC-PF). | Baseline, 3 and 6 months | WOMAC-PF is a patient reported outcome with 17 items. Each item is scored on a 5-point Likert-type Scale with descriptors from 0-4 (none, mild, moderate, severe, and extreme difficulty) and summed for a maximum score of 68. Higher scores indicate worse physical function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite Score of Performed-based Tests of Physical Function. | Baseline, 3 and 6 months | Scores on 6 performance-based tests (i.e., the 6-minute walk test, 40-meter gait speed, stair ascend/descend test, single leg stance balance test, chair stand test, and floor sitting-rising) were combined into a composite score formed with the unit-weighted Z scores of constituent tests to provide a more representative and stable measure of the subjects' underlying functional performance. The unit weights refer to averaging standardized scores (e.g., the scores for each performance-based test are converted to Z-scores before applying equal weights). Higher Z-scores represent better functional performance. The Z-scores for each participant can be interpreted as deviations from the baseline average of the whole group. We considered a change in Z-score of 0.2 as clinically important because it represents approximately 20% of a standard deviation relative to the baseline average of the whole group. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Physical Activity Energy Expenditure - Measured by Portable Activity Monitor (SenseWear). | Baseline, 3 and 6 months | Real-time measure of daily energy expenditure physical activity assessed by portable activity monitor. |
Countries
United States
Participant flow
Recruitment details
Potential subjects were identified from their surgeons' office or via public announcement in the greater Pittsburgh area, from December 2014 through February 2017. If interested in the study, subjects called the research team to obtain more information about the study, and were then screened for study eligibility.
Pre-assignment details
A total of 1372 subjects called for study information: 89 could not be contacted and 1283 were screened over the telephone. From those, 1032 were not eligible/willing to participate and 251 completed in-person screening. Eleven subjects failed in-person screening, resulting in 240 eligible subjects that were randomized into one of the study arms.
Participants by arm
| Arm | Count |
|---|---|
| Clinic-based Outpatient Exercise Group Subjects participated in supervised sessions (clinic-based) of exercise followed by a home exercise program 2 times per week during 3 months. Each exercise session lasted about 60 minutes. Treatment sessions utilized a pragmatic approach and included exercises designed to increase muscular strength, low impact cardiovascular exercise, range of movement, and activity for daily living skills. | 96 |
| Community-based Exercise Group Subjects attended to exercise classes (community-based) 2 times per week during 3 months. The exercise classes lasted approximately 60 minutes. The group exercise classes consisted of a variety of exercises designed to increase general muscular strength, low impact aerobic exercise, range of movement, and activity for daily living. | 96 |
| Wait-listed Usual Medical Care Wait-listed usual medical care - no intervention provided by study. | 48 |
| Total | 240 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 7 | 2 |
Baseline characteristics
| Characteristic | Clinic-based Outpatient Exercise Group | Community-based Exercise Group | Wait-listed Usual Medical Care | Total |
|---|---|---|---|---|
| Age, Continuous | 69 years STANDARD_DEVIATION 6.3 | 70 years STANDARD_DEVIATION 7 | 70 years STANDARD_DEVIATION 6.6 | 70 years STANDARD_DEVIATION 6.6 |
| Body Mass Index (BMI) | 30.8 kg/m^2 STANDARD_DEVIATION 5.3 | 31.1 kg/m^2 STANDARD_DEVIATION 6.3 | 31.5 kg/m^2 STANDARD_DEVIATION 5.1 | 31.1 kg/m^2 STANDARD_DEVIATION 5.7 |
| Cumulative Illness Rating Scale | 4.3 Number of comorbidities STANDARD_DEVIATION 2 | 4.4 Number of comorbidities STANDARD_DEVIATION 1.7 | 4.6 Number of comorbidities STANDARD_DEVIATION 1.9 | 4.4 Number of comorbidities STANDARD_DEVIATION 1.9 |
| Education Complete college or technical training | 59 Participants | 57 Participants | 31 Participants | 147 Participants |
| Education Less than college | 31 Participants | 33 Participants | 12 Participants | 76 Participants |
| Education Other/missing | 6 Participants | 6 Participants | 5 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 96 Participants | 95 Participants | 47 Participants | 238 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Marital status Divorced | 18 Participants | 12 Participants | 7 Participants | 37 Participants |
| Marital status Married | 64 Participants | 62 Participants | 31 Participants | 157 Participants |
| Marital status Never Married | 4 Participants | 8 Participants | 3 Participants | 15 Participants |
| Marital status Other | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Marital status Widowed | 8 Participants | 14 Participants | 6 Participants | 28 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 18 Participants | 11 Participants | 39 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 86 Participants | 77 Participants | 37 Participants | 200 Participants |
| Sex: Female, Male Female | 59 Participants | 58 Participants | 31 Participants | 148 Participants |
| Sex: Female, Male Male | 37 Participants | 38 Participants | 17 Participants | 92 Participants |
| Surgical Knee Flexion | 124 degrees STANDARD_DEVIATION 11 | 123 degrees STANDARD_DEVIATION 11 | 124 degrees STANDARD_DEVIATION 10 | 124 degrees STANDARD_DEVIATION 11 |
| Surgical knee pain | 2.7 units on a scale STANDARD_DEVIATION 2.1 | 2.3 units on a scale STANDARD_DEVIATION 1.7 | 2.2 units on a scale STANDARD_DEVIATION 1.8 | 2.4 units on a scale STANDARD_DEVIATION 1.9 |
| Total Knee Replacement Due To Inflammatory Arthritis | 4 Participants | 4 Participants | 0 Participants | 8 Participants |
| Total Knee Replacement Due To Osteoarthritis | 92 Participants | 92 Participants | 48 Participants | 232 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 96 | 0 / 96 | 0 / 48 |
| other Total, other adverse events | 39 / 96 | 42 / 96 | 22 / 48 |
| serious Total, serious adverse events | 5 / 96 | 4 / 96 | 5 / 48 |
Outcome results
Primary
The Western Ontario and McMaster Universities Osteoarthritis Index Physical Function (WOMAC-PF).
WOMAC-PF is a patient reported outcome with 17 items. Each item is scored on a 5-point Likert-type Scale with descriptors from 0-4 (none, mild, moderate, severe, and extreme difficulty) and summed for a maximum score of 68. Higher scores indicate worse physical function.
Time frame: Baseline, 3 and 6 months
Population: Intention-to-treat approach was used among participants with follow-up data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Clinic-based Outpatient Exercise Group | The Western Ontario and McMaster Universities Osteoarthritis Index Physical Function (WOMAC-PF). | 3 months | 10.1 units on a scale | Standard Deviation 6.6 |
| Clinic-based Outpatient Exercise Group | The Western Ontario and McMaster Universities Osteoarthritis Index Physical Function (WOMAC-PF). | Baseline | 20.9 units on a scale | Standard Deviation 7.9 |
| Clinic-based Outpatient Exercise Group | The Western Ontario and McMaster Universities Osteoarthritis Index Physical Function (WOMAC-PF). | 6 months | 9.8 units on a scale | Standard Deviation 7.2 |
| Community-based Exercise Group | The Western Ontario and McMaster Universities Osteoarthritis Index Physical Function (WOMAC-PF). | Baseline | 20.4 units on a scale | Standard Deviation 7.4 |
| Community-based Exercise Group | The Western Ontario and McMaster Universities Osteoarthritis Index Physical Function (WOMAC-PF). | 3 months | 12.2 units on a scale | Standard Deviation 7.9 |
| Community-based Exercise Group | The Western Ontario and McMaster Universities Osteoarthritis Index Physical Function (WOMAC-PF). | 6 months | 10.8 units on a scale | Standard Deviation 7.9 |
| Wait-listed Usual Medical Care | The Western Ontario and McMaster Universities Osteoarthritis Index Physical Function (WOMAC-PF). | Baseline | 20.2 units on a scale | Standard Deviation 7.9 |
| Wait-listed Usual Medical Care | The Western Ontario and McMaster Universities Osteoarthritis Index Physical Function (WOMAC-PF). | 6 months | 11.8 units on a scale | Standard Deviation 7.5 |
| Wait-listed Usual Medical Care | The Western Ontario and McMaster Universities Osteoarthritis Index Physical Function (WOMAC-PF). | 3 months | 11.9 units on a scale | Standard Deviation 7.6 |
p-value: 0.07198.3% CI: [-4.9, 0.7]Mixed Models Analysis
Comparison: Contrasts from a linear mixed models analysis at 6 months adjusted by baseline age, gender, BMI, WOMAC-PF, knee flexion.p-value: 0.07498.3% CI: [-5, 0.7]Mixed Models Analysis
Comparison: Contrasts from a linear mixed models analysis at 3 months adjusted by baseline age, gender, BMI, WOMAC-PF, knee flexion.p-value: 0.9398.3% CI: [-2.7, 2.9]Mixed Models Analysis
p-value: 0.49198.3% CI: [-3.7, 2]Mixed Models Analysis
p-value: 0.02198.3% CI: [-4.5, 0.1]Mixed Models Analysis
p-value: 0.17998.3% CI: [-3.6, 1]Mixed Models Analysis
Secondary
Composite Score of Performed-based Tests of Physical Function.
Scores on 6 performance-based tests (i.e., the 6-minute walk test, 40-meter gait speed, stair ascend/descend test, single leg stance balance test, chair stand test, and floor sitting-rising) were combined into a composite score formed with the unit-weighted Z scores of constituent tests to provide a more representative and stable measure of the subjects' underlying functional performance. The unit weights refer to averaging standardized scores (e.g., the scores for each performance-based test are converted to Z-scores before applying equal weights). Higher Z-scores represent better functional performance. The Z-scores for each participant can be interpreted as deviations from the baseline average of the whole group. We considered a change in Z-score of 0.2 as clinically important because it represents approximately 20% of a standard deviation relative to the baseline average of the whole group.
Time frame: Baseline, 3 and 6 months
Population: Intention-to-treat approach was used among participants with follow-up data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Clinic-based Outpatient Exercise Group | Composite Score of Performed-based Tests of Physical Function. | 3 months | 0.49 Z-score | Standard Deviation 0.7 |
| Clinic-based Outpatient Exercise Group | Composite Score of Performed-based Tests of Physical Function. | Baseline | 0.02 Z-score | Standard Deviation 0.8 |
| Clinic-based Outpatient Exercise Group | Composite Score of Performed-based Tests of Physical Function. | 6 months | 0.5 Z-score | Standard Deviation 0.8 |
| Community-based Exercise Group | Composite Score of Performed-based Tests of Physical Function. | 3 months | 0.3 Z-score | Standard Deviation 0.8 |
| Community-based Exercise Group | Composite Score of Performed-based Tests of Physical Function. | Baseline | -0.06 Z-score | Standard Deviation 0.8 |
| Community-based Exercise Group | Composite Score of Performed-based Tests of Physical Function. | 6 months | 0.36 Z-score | Standard Deviation 0.9 |
| Wait-listed Usual Medical Care | Composite Score of Performed-based Tests of Physical Function. | Baseline | -0.11 Z-score | Standard Deviation 0.7 |
| Wait-listed Usual Medical Care | Composite Score of Performed-based Tests of Physical Function. | 6 months | 0.25 Z-score | Standard Deviation 0.7 |
| Wait-listed Usual Medical Care | Composite Score of Performed-based Tests of Physical Function. | 3 months | 0.13 Z-score | Standard Deviation 0.7 |
p-value: <0.000198.3% CI: [0.1, 0.4]Mixed Models Analysis
p-value: 0.01298.3% CI: [0.01, 0.4]Mixed Models Analysis
p-value: 0.00598.3% CI: [0.02, 0.3]Mixed Models Analysis
p-value: 0.05298.3% CI: [-0.003, 0.3]Mixed Models Analysis
p-value: 0.01598.3% CI: [0.02, 0.3]Mixed Models Analysis
p-value: 0.48998.3% CI: [-0.003, 0.3]Mixed Models Analysis
Other Pre-specified
Physical Activity Energy Expenditure - Measured by Portable Activity Monitor (SenseWear).
Real-time measure of daily energy expenditure physical activity assessed by portable activity monitor.
Time frame: Baseline, 3 and 6 months
Population: Intention-to-treat approach was used among participants with follow-up data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Clinic-based Outpatient Exercise Group | Physical Activity Energy Expenditure - Measured by Portable Activity Monitor (SenseWear). | 3 months | 566 Kcal/day | Standard Deviation 451 |
| Clinic-based Outpatient Exercise Group | Physical Activity Energy Expenditure - Measured by Portable Activity Monitor (SenseWear). | Baseline | 511 Kcal/day | Standard Deviation 411 |
| Clinic-based Outpatient Exercise Group | Physical Activity Energy Expenditure - Measured by Portable Activity Monitor (SenseWear). | 6 months | 538 Kcal/day | Standard Deviation 403 |
| Community-based Exercise Group | Physical Activity Energy Expenditure - Measured by Portable Activity Monitor (SenseWear). | 3 months | 547 Kcal/day | Standard Deviation 407 |
| Community-based Exercise Group | Physical Activity Energy Expenditure - Measured by Portable Activity Monitor (SenseWear). | Baseline | 541 Kcal/day | Standard Deviation 419 |
| Community-based Exercise Group | Physical Activity Energy Expenditure - Measured by Portable Activity Monitor (SenseWear). | 6 months | 480 Kcal/day | Standard Deviation 420 |
| Wait-listed Usual Medical Care | Physical Activity Energy Expenditure - Measured by Portable Activity Monitor (SenseWear). | Baseline | 459 Kcal/day | Standard Deviation 352 |
| Wait-listed Usual Medical Care | Physical Activity Energy Expenditure - Measured by Portable Activity Monitor (SenseWear). | 6 months | 509 Kcal/day | Standard Deviation 518 |
| Wait-listed Usual Medical Care | Physical Activity Energy Expenditure - Measured by Portable Activity Monitor (SenseWear). | 3 months | 525 Kcal/day | Standard Deviation 411 |
p-value: 0.94395% CI: [-106, 114]Mixed Models Analysis
p-value: 0.81495% CI: [-112, 142]Mixed Models Analysis
p-value: 0.78795% CI: [-125, 95]Mixed Models Analysis
p-value: 0.58195% CI: [-164, 92]Mixed Models Analysis
p-value: 0.67695% CI: [-71, 109]Mixed Models Analysis
p-value: 0.3395% CI: [-52, 154]Mixed Models Analysis