Post-Operative Pain Following Total Knee Arthroplasty
Conditions
Keywords
Pulsed Electromagnetic Energy Fields, Total Knee Arthroplasty, Pain Intensity
Brief summary
The purpose of this study is to investigate whether pulsed electromagnetic energy field (PEMF) therapy is effective in the treatment of persistent pain following total knee arthroplasty (TKA)
Detailed description
This is a multi-site randomized, double-blinded, parallel-group prospective pilot study of the analgesic effectiveness of twice-daily PEMF therapy in the treatment of persistent post-operative pain following Total Knee Arthroplasty (TKA). Following a run-in period of 10 days to collect their baseline pain intensity scores, activity levels and opioid consumption, eligible subjects will be randomized in a 2:1 ratio to receive therapy with an active PEMF device or an identical inactive Sham device. Subjects will self-treat twice daily for 60 days while at home. Subjects will collect electronic patient-reported outcome (ePRO) data each morning through Day 75. Subjects will be evaluated at the research center for Interim Visits at Day 21, Day 41, Day 61 and Day 75 for assessment of safety, concomitant medications, range of motion, weight, peripheral edema, and quality of life outcomes. At Day 90, Day 150, and Day 240 assessment of pain intensity, opioid consumption, safety, review of concomitant medications and interval history will be performed, with data collected via telephone contact.
Interventions
DEVICEPulsed Electromagnetic Field Device (Provant)
The PEMF device delivers non-thermal, non-ionizing pulsed electromagnetic energy to the target tissue, using 27.12 megahertz pulses lasting 42 microseconds and delivered 1000 times per second. The system generates an electromagnetic field that is continuously monitored and regulated to ensure consistent dosing. The therapeutic electromagnetic field is delivered by means of an applicator pad that is placed against the treatment site. The active and sham devices will be identical in appearance and all other physical characteristics in order to maintain the masking of the treatment.
DEVICESham Pulsed Electromagnetic Field Device
The Sham device will be identical in appearance, physical characteristics and operation to the Active device.
Sponsors
Regenesis Biomedical, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject age is greater or equal to 18 years. 2. Subject has undergone a total knee replacement for the treatment of osteoarthritis, and has persistent post-operative pain in the index knee for \> 3 months and \< 36 months following surgery. 3. Subject has been receiving medication for persistent post-operative knee pain, including opioid or non-opioid analgesic medication that is administered on an as needed (prn) basis, and is on a stable analgesic dosing regimen (i.e. the same medications and dosages) for \> 30 days prior to the screening visit. 4. Mean Pain Intensity (calculated as the mean of the daily average pain intensity scores) is ≥3 and \< 9 as measured on Numeric Pain Rating Scale (NPRS) during the run-in phase. 5. Subject has completed a minimum of 80% (8 of 10 possible) of the pain intensity assessments during the run-in phase. 6. Subject is willing and able to wear an activity meter from the screening visit through Day 75. 7. Subject is able to access an internet browser in the home environment. 8. Subject is willing and able to give written informed consent and to comply with all parts of the study protocol. 9. Female Subjects must be post menopausal, surgically sterile, abstinent, or practicing (or agree to practice) an effective method of birth control if they are sexually active for the duration of the study. (Effective methods of birth control include prescription hormonal contraceptives, intrauterine devices, double-barrier methods, and/or male partner sterilization).
Exclusion criteria
1. Subject has undergone simultaneous bilateral knee arthroplasty or revision arthroplasty on the index knee. 2. Subject requires revision surgery prior to Day 75. 3. Subject has undergone manipulation under anesthesia of the index knee or any local injection into the index knee within 30 days prior to the Screening Visit, or within 6 weeks prior to the Screening Visit for long acting lidocaine injection products. 4. Subject has received any investigational drug or device within 30 days prior to the Screening Visit or is enrolled in another clinical trial. 5. Subjects consuming an average of \> 100 mg oral Morphine Sulfate equivalents per day during the run-in phase. 6. Subject has evidence on physical or radiological exam of joint instability or infection involving the index knee. 7. Passive range of motion demonstrates maximal flexion of the index knee \< 90 degrees or maximal extension of the index knee \< -10 degrees. 8. Body Mass Index (BMI) \< 19 kg/m2, or \> 38 kg/m2. 9. Subject has a history of any uncontrolled medical illness that in the investigator's judgment places the subject at unacceptable risk for receipt of Provant therapy. 10. Subject has an ongoing painful condition that in the opinion of the Investigator might have a confounding influence on the safety or effectiveness analysis for this study. 11. Use of systemic corticosteroids within 2 months of the Screening visit. 12. Subject anticipates the need for surgery of any type through the Day 75 visit. 13. Subjects whom, in the judgment of the Investigator, have serious psychosocial co-morbidities. 14. History of drug or alcohol abuse within one year prior to screening. 15. Subject has a history of malignancy within the past five years other than successfully treated non-metastatic basal cell or squamous cell carcinomas of the skin in the treatment area and/or localized carcinoma in situ of the cervix. 16. Subject has an implanted pacemaker, defibrillator, neurostimulator, spinal cord stimulator, bone stimulator, cochlear implant, or other implanted device with an implanted metal lead(s). 17. Existing or planned pregnancy. 18. Subject has been previously treated with study device. 19. Subject is in current litigation related to the index knee or is receiving Worker's Compensation for an injury related to the index knee. 20. Subject is unwilling or unable to follow study instructions, comply with the treatment regimen, study visits, and ePRO assessments. 21. Standard deviation around the mean of the average pain intensity scores during the run-in period is \>2.0.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pain Intensity | Assessed at Day 60 as compared to Baseline | Percent change from Baseline in Pain Intensity (PI): a validated 11-point Numeric Pain Rating Scale (NPRS) with scores (0-10) collected as patient-reported outcomes on an electronic diary (ePRO). A score of 0 represents 'No Pain' while a score of 10 represents Worst Pain Imaginable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Beck Depression Inventory (BDI) | Responders at Day 75 (compared to baseline) | Responders: Defined as subjects with a 5-point decrease in Beck Depression Inventory (BDI) score. BDI is a validated self-reported assessment of current symptoms of depressive disorders, with total scores ranging from 0 to 63. The BDI scale consists of 21 groups of statements with each score/response ranging from 0 to 3. Higher scores represent greater depression. The BDI was conducted at baseline prior to study device treatments and again at Day 61. |
| Patient Global Impression of Change (PGIC) | Day 75 | Responder Analysis at Day 75 (patents stating they are Improved to Much Improved) using the Patient Global Impression of Change (PGIC). PGIC is a 7-point validated categorical scale of overall change in status since initiation of treatment with the study device. PGIC allows subjects to integrate into one overall evaluation the different aspects of their response to treatment, including pain reduction, improvement in functioning and side effects. Subjects select one of the following response at the end of treatment: Very Much Worse, Much Worse, Minimally Worse, No Change, Minimally Improved, Improved, or Much Improved. |
| Analgesic Consumption | Day 56 to Day 60 (compared to baseline) | Consumption of opioid analgesics in the preceding 24 hours will be self-reported by the subject in the ePRO diary on a daily basis during the 10-day run-in period, treatment period and through Day 75. The results below display the difference in opioid analgesic consumption from baseline to Day 56-60. Subject recorded the number of tablets consumed. |
| Mean Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) | Mean change from Day 0 to Day 75 | Knee Injury and Osteoarthritis Outcome Score (KOOS): a validated knee-specific instrument that measures the short-term and long-term symptoms and function associated with knee injury. KOOS consists of 5 categories: pain, other symptoms, function in daily living, function in sport and recreation, and knee related quality of life. Patients are asked to answer questions relating to these categories and respond with Never/None/Not at all, Rarely/Monthly/Mild, Sometimes/Moderate/Weekly, Often/Severe/Daily or Always/Extreme/Totally/Constantly. Each response gets a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The mean change in score from baseline to Day 75 is displayed below. |
| Change From Baseline in Peripheral Edema - Maximal Circumference of Calf (cm) | Day 75 | The maximal circumference of the calf and circumference of the thigh at 10 cm and 15 cm cranial to the superior pole of the patella of the index knee will be measured using a tape measure. |
| Change in Pain Intensity - Average Pain Intensity | At Days 75, 90, 150 and 240, as compared to Baseline | Pain Intensity (PI): a validated 11-point Numeric Pain Rating Scale (NPRS) with scores (0-10) collected as patient-reported outcomes on an electronic diary (ePRO). |
| Change From Baseline in Range of Motion (ROM) | Days 0 (Baseline) and Day 75 | The degree of passive (movement of the knee with the aid of study personnel) and active (subject moving the knee) knee flexion and extension tolerated by the subject will be recorded. ROM will be assessed in the sitting position using a goniometer. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pulsed Electromagnetic Field Device Pulsed Electromagnetic Field therapy device; self-administered at home twice daily for 30 minutes.
Pulsed Electromagnetic Field Device (Provant): The PEMF device delivers non-thermal, non-ionizing pulsed electromagnetic energy to the target tissue, using 27.12 megahertz pulses lasting 42 microseconds and delivered 1000 times per second. The system generates an electromagnetic field that is continuously monitored and regulated to ensure consistent dosing. The therapeutic electromagnetic field is delivered by means of an applicator pad that is placed against the treatment site. The active and sham devices will be identical in appearance and all other physical characteristics in order to maintain the masking of the treatment. | 24 |
| Sham Pulsed Electromagnetic Field Device Inactive Pulsed Electromagnetic Field Therapy device; self-administered at home twice daily for 30 minutes.
Sham Pulsed Electromagnetic Field Device: The Sham device will be identical in appearance, physical characteristics and operation to the Active device. | 11 |
| Total | 35 |
Baseline characteristics
| Characteristic | Sham Pulsed Electromagnetic Field Device | Total | Pulsed Electromagnetic Field Device |
|---|---|---|---|
| Age, Continuous | 63.82 Years | 62.86 Years | 62.42 Years |
| BMI | 31.7 kg/m^2 | 31.42 kg/m^2 | 31.3 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 31 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Pain Catastrophizing Score | 17.7 units on a scale | 18.59 units on a scale | 19 units on a scale |
| PainDETECT Questionnaire | 12.7 units on a scale | 12.8 units on a scale | 12.8 units on a scale |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 32 Participants | 22 Participants |
| Sex: Female, Male Female | 7 Participants | 24 Participants | 17 Participants |
| Sex: Female, Male Male | 4 Participants | 11 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 24 | 4 / 11 |
| serious Total, serious adverse events | 0 / 24 | 0 / 11 |
Outcome results
Primary
Change in Pain Intensity
Percent change from Baseline in Pain Intensity (PI): a validated 11-point Numeric Pain Rating Scale (NPRS) with scores (0-10) collected as patient-reported outcomes on an electronic diary (ePRO). A score of 0 represents 'No Pain' while a score of 10 represents Worst Pain Imaginable.
Time frame: Assessed at Day 60 as compared to Baseline
Population: Discrepancy in Numbers of Participants Analyzed is due to the number of subjects completing the Day 60 assessment. Not all subjects that were enrolled and had baseline data captured completed the Day 60 assessment. Subjects without a Day 60 assessment were left out of the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pulsed Electromagnetic Field Device | Change in Pain Intensity | -30.9 Units on a scale | Standard Deviation 37.99 |
| Sham Pulsed Electromagnetic Field Device | Change in Pain Intensity | -29.7 Units on a scale | Standard Deviation 30.58 |
Secondary
Analgesic Consumption
Consumption of opioid analgesics in the preceding 24 hours will be self-reported by the subject in the ePRO diary on a daily basis during the 10-day run-in period, treatment period and through Day 75. The results below display the difference in opioid analgesic consumption from baseline to Day 56-60. Subject recorded the number of tablets consumed.
Time frame: Day 56 to Day 60 (compared to baseline)
Population: Number of Participants Analyzed differs from numbers above due to the number of subjects reporting opioid analgesic consumption in their ePRO diary.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pulsed Electromagnetic Field Device | Analgesic Consumption | -20.6 Number of tablets taken | Standard Deviation 18.04 |
| Sham Pulsed Electromagnetic Field Device | Analgesic Consumption | -22.2 Number of tablets taken | Standard Deviation 16.78 |
Secondary
Beck Depression Inventory (BDI)
Responders: Defined as subjects with a 5-point decrease in Beck Depression Inventory (BDI) score. BDI is a validated self-reported assessment of current symptoms of depressive disorders, with total scores ranging from 0 to 63. The BDI scale consists of 21 groups of statements with each score/response ranging from 0 to 3. Higher scores represent greater depression. The BDI was conducted at baseline prior to study device treatments and again at Day 61.
Time frame: Responders at Day 75 (compared to baseline)
Population: Discrepancy in Numbers of Participants Analyzed is due to the number of subjects completing the Day 75 assessment. Not all subjects that were enrolled and had baseline data captured completed the Day 75 assessment. Subjects without a Day 75 assessment were left out of the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pulsed Electromagnetic Field Device | Beck Depression Inventory (BDI) | 3 Participants |
| Sham Pulsed Electromagnetic Field Device | Beck Depression Inventory (BDI) | 2 Participants |
Secondary
Change From Baseline in Peripheral Edema - Maximal Circumference of Calf (cm)
The maximal circumference of the calf and circumference of the thigh at 10 cm and 15 cm cranial to the superior pole of the patella of the index knee will be measured using a tape measure.
Time frame: Day 75
Population: Discrepancy in Numbers of Participants Analyzed is due to the number of subjects completing the Day 75 assessment. Not all subjects that were enrolled and had baseline data captured completed the Day 75 assessment. Subjects without a Day 75 assessment were left out of the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pulsed Electromagnetic Field Device | Change From Baseline in Peripheral Edema - Maximal Circumference of Calf (cm) | .1 cm | Standard Deviation 1.46 |
| Sham Pulsed Electromagnetic Field Device | Change From Baseline in Peripheral Edema - Maximal Circumference of Calf (cm) | -.1 cm | Standard Deviation 0.75 |
Secondary
Change From Baseline in Range of Motion (ROM)
The degree of passive (movement of the knee with the aid of study personnel) and active (subject moving the knee) knee flexion and extension tolerated by the subject will be recorded. ROM will be assessed in the sitting position using a goniometer.
Time frame: Days 0 (Baseline) and Day 75
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pulsed Electromagnetic Field Device | Change From Baseline in Range of Motion (ROM) | Change from Baseline - Passive Extension ROM-Day75 | -.5 degrees of motion | Standard Deviation 3.72 |
| Pulsed Electromagnetic Field Device | Change From Baseline in Range of Motion (ROM) | Passive Extension ROM - Baseline | 3.2 degrees of motion | Standard Deviation 2.81 |
| Pulsed Electromagnetic Field Device | Change From Baseline in Range of Motion (ROM) | Active Extension ROM - Baseline | 4.4 degrees of motion | Standard Deviation 3.37 |
| Pulsed Electromagnetic Field Device | Change From Baseline in Range of Motion (ROM) | Change from Baseline - Active Extension ROM-Day75 | -.8 degrees of motion | Standard Deviation 3.49 |
| Pulsed Electromagnetic Field Device | Change From Baseline in Range of Motion (ROM) | Change from Basline - Passivie Flexion ROM-Day 75 | 3.0 degrees of motion | Standard Deviation 9.19 |
| Pulsed Electromagnetic Field Device | Change From Baseline in Range of Motion (ROM) | Passive Flexion ROM - Baseline | 110.3 degrees of motion | Standard Deviation 11.44 |
| Pulsed Electromagnetic Field Device | Change From Baseline in Range of Motion (ROM) | Active Flexion ROM - Baseline | 107.7 degrees of motion | Standard Deviation 10.35 |
| Pulsed Electromagnetic Field Device | Change From Baseline in Range of Motion (ROM) | Change from Baseline - Active Felexion ROM -Day 75 | 3.7 degrees of motion | Standard Deviation 9.19 |
| Sham Pulsed Electromagnetic Field Device | Change From Baseline in Range of Motion (ROM) | Change from Baseline - Active Felexion ROM -Day 75 | 5.2 degrees of motion | Standard Deviation 7.69 |
| Sham Pulsed Electromagnetic Field Device | Change From Baseline in Range of Motion (ROM) | Change from Baseline - Passive Extension ROM-Day75 | .4 degrees of motion | Standard Deviation 3.09 |
| Sham Pulsed Electromagnetic Field Device | Change From Baseline in Range of Motion (ROM) | Change from Basline - Passivie Flexion ROM-Day 75 | 4.6 degrees of motion | Standard Deviation 4.93 |
| Sham Pulsed Electromagnetic Field Device | Change From Baseline in Range of Motion (ROM) | Passive Extension ROM - Baseline | 3.6 degrees of motion | Standard Deviation 4.13 |
| Sham Pulsed Electromagnetic Field Device | Change From Baseline in Range of Motion (ROM) | Active Flexion ROM - Baseline | 106.8 degrees of motion | Standard Deviation 14.85 |
| Sham Pulsed Electromagnetic Field Device | Change From Baseline in Range of Motion (ROM) | Active Extension ROM - Baseline | 4.2 degrees of motion | Standard Deviation 3.8 |
| Sham Pulsed Electromagnetic Field Device | Change From Baseline in Range of Motion (ROM) | Passive Flexion ROM - Baseline | 110.0 degrees of motion | Standard Deviation 16.05 |
| Sham Pulsed Electromagnetic Field Device | Change From Baseline in Range of Motion (ROM) | Change from Baseline - Active Extension ROM-Day75 | .6 degrees of motion | Standard Deviation 2.4 |
Secondary
Change in Pain Intensity - Average Pain Intensity
Pain Intensity (PI): a validated 11-point Numeric Pain Rating Scale (NPRS) with scores (0-10) collected as patient-reported outcomes on an electronic diary (ePRO).
Time frame: At Days 75, 90, 150 and 240, as compared to Baseline
Population: Data were not collected.
Secondary
Mean Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS)
Knee Injury and Osteoarthritis Outcome Score (KOOS): a validated knee-specific instrument that measures the short-term and long-term symptoms and function associated with knee injury. KOOS consists of 5 categories: pain, other symptoms, function in daily living, function in sport and recreation, and knee related quality of life. Patients are asked to answer questions relating to these categories and respond with Never/None/Not at all, Rarely/Monthly/Mild, Sometimes/Moderate/Weekly, Often/Severe/Daily or Always/Extreme/Totally/Constantly. Each response gets a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The mean change in score from baseline to Day 75 is displayed below.
Time frame: Mean change from Day 0 to Day 75
Population: Discrepancy in Numbers of Participants Analyzed is due to the number of subjects completing the Day 75 assessment. Not all subjects that were enrolled and had baseline data captured completed the Day 75 assessment. Subjects without a Day 75 assessment were left out of the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pulsed Electromagnetic Field Device | Mean Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) | 9.2 units on a scale | Standard Deviation 19.02 |
| Sham Pulsed Electromagnetic Field Device | Mean Change From Baseline in Knee Injury and Osteoarthritis Outcome Score (KOOS) | 8.9 units on a scale | Standard Deviation 14.17 |
Secondary
Patient Global Impression of Change (PGIC)
Responder Analysis at Day 75 (patents stating they are Improved to Much Improved) using the Patient Global Impression of Change (PGIC). PGIC is a 7-point validated categorical scale of overall change in status since initiation of treatment with the study device. PGIC allows subjects to integrate into one overall evaluation the different aspects of their response to treatment, including pain reduction, improvement in functioning and side effects. Subjects select one of the following response at the end of treatment: Very Much Worse, Much Worse, Minimally Worse, No Change, Minimally Improved, Improved, or Much Improved.
Time frame: Day 75
Population: Discrepancy in Numbers of Participants Analyzed is due to the number of subjects completing the Day 75 assessment. Not all subjects that were enrolled and had baseline data captured completed the Day 75 assessment. Subjects without a Day 75 assessment were left out of the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pulsed Electromagnetic Field Device | Patient Global Impression of Change (PGIC) | 5 Participants |
| Sham Pulsed Electromagnetic Field Device | Patient Global Impression of Change (PGIC) | 2 Participants |