Electrical Stimulation for the Treatment of Pain Following Total Knee Arthroplasty Using the SPRINT Beta System

Study Overview
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Brief Summary
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The purpose of this study is to determine if electrical stimulation (small levels of electricity) in addition to the standard of care can safely and effectively reduce pain following total knee replacement more than the standard of care, alone. This study involves a device called the SPRINT Beta System. The SPRINT Beta System delivers mild electrical stimulation to nerves in the leg that received the knee replacement. The SPRINT Beta System includes a small wire (called a lead) that is placed through the skin in the upper leg. It also includes a device worn on the body that delivers stimulation (called the SPRINT Beta Stimulator). About half the subjects in this study will receive the SPRINT Beta system (treatment group) and half will not (control group). Both groups will receive the standard of care.

Official Title
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A Prospective, Comparative Effectiveness Randomized Controlled Trial of SPR Peripheral Nerve Stimulation (PNS) Therapy for the Treatment of Pain Following Total Knee Arthroplasty (TKA) Utilizing Preoperative Lead Placement

Conditions
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Pain, Total Knee Replacement, Total Knee Arthroplasty, Postoperative Pain, Orthopedic Disorder

Intervention / Treatment
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* Device: SPRINT Beta System


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Scheduled to undergo a primary unilateral total knee replacement procedure Key Exclusion Criteria: Body Mass Index > 40 kg/m2 Conditions that place the subject at increased risk of infection History of valvular heart disease Implanted electronic device Bleeding disorder Allergy to skin surface electrodes and/or medical-grade adhesive tapes Pregnant

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 90 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Half of the subjects enrolled will be randomized (like flipping a coin) to the treatment group and half will be randomized to the control group. Both groups will receive the standard of care for pain management following total knee replacement surgery. Subjects in the treatment group will receive SPR's SPRINT Beta Peripheral Nerve Stimulation (PNS) System in addition to standard of care.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group (SPRINT Beta System)<br>Subjects in the treatment group will have up to 2 leads placed in their leg that underwent total knee replacement, will use the SPRINT Beta System, and will receive electrical stimulation in addition to the standard of care. | Device: SPRINT Beta System<br>* The SPRINT Beta System is an Investigational Device which delivers mild electrical stimulation to nerves in the leg that underwent lead placement. The SPRINT Beta System includes a small wire (called a Lead) that is placed through the skin in the upper leg. It also includes a device worn on the body that delivers stimulation (called the SPRINT Beta Stimulator).<br>* Other names: SPRINT System;|
| No Intervention: Control Group<br>Subjects in the control group will receive the standard of care. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Knee Pain While Walking | All subjects were asked to complete daily diaries to record their average pain intensity while walking during the past 24 hours on each day of a 7-day period using an 11-point numerical rating scale where 0 represents No Pain and 10 represents Pain as bad as you can imagine. For each subject, the mean score for each diary period was calculated and a mean of all four diary periods was calculated (weeks 1-4). The mean group scores for weeks 1-4 are reported. | Postoperative Day 0 to 28 (first 4 weeks following Total Knee Arthroplasty (TKA) | 
| Number of Subjects That Experienced at Least One Study-Related Adverse Event | At each study visit following the baseline assessment at Visit 1, subjects were questioned if any changes in their medical status or condition has occurred since their previous visit. If the subject experienced a change that was an adverse event, an Adverse Event Form was completed by the site. The number of Treatment Group subjects that experienced at least one study-related adverse event is reported here. | 30 months (from when the first Treatment Group subject enrolled to when the last Treatment Group subject completed the study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Knee Pain Over the Last 24 Hours | All subjects were asked to complete daily diaries to track their average pain intensity during the past 24 hours over a 7-day period on an 11-point numerical rating scale where 0 represents No Pain and 10 represents Pain as bad as you can imagine. The average score for each diary period was calculated across subjects, and the mean score for weeks 1-4 is reported. | Postoperative Day 0 to 28 (first 4 weeks following Total Knee Arthroplasty (TKA)) | 
| Average Knee Pain at Rest | All subjects were asked to complete daily diaries to track their average pain intensity at rest during the past 24 hours over a 7-day period on an 11-point numerical rating scale where 0 represents No Pain and 10 represents Pain as bad as you can imagine. The average score for each diary period was calculated across subjects, and the mean score for weeks 1-4 is reported. | Postoperative Day 0 to 28 (first 4 weeks following Total Knee Arthroplasty (TKA)) | 
| Pain Right Now as Measured by the Brief Pain Inventory | Subjects were asked to rate their pain right now on an 11-point numerical scale where 0 represents No Pain and 10 represents Pain as bad as you can imagine. The median score for each time point is reported. Baseline is considered Visit 2a (Lead Placement) for Treatment Group subjects and Visit 2b for Control Group subjects. For Treatment Group subjects for Visits 3, 4, 6, and 8, pain right now was assessed while peripheral nerve stimulation was on for at least one Lead. For Visit 4, the score reported during the last in-hospital day was used. | Baseline (Visit 2a/2b), Visit 3 (Day of Total Knee Arthroplasty (TKA)), Visit 4 (in-hospital), Visit 6 (2-weeks post TKA), and Visit 8 (4-weeks post TKA) | 
| Amount of Analgesic Usage | Subjects recorded the amount/type of analgesics used in daily diaries. Narcotic usage was converted into morphine milligram equivalents (MME). Diaries were collected at various visits and were translated into post-operative days. The average MME was calculated for each subject for the first 28 days (4 weeks) following surgery, and the median of these averages across subjects was determined. If subjects had ceased opioid use (per the Recovery Milestones log), then missing scores following the date of opioid cessation were replaced with 0 MME. If diary entries were missing but the subject had not yet reported opioid cessation, then the missing value was replaced with the mean usage of the available days for the corresponding week. Subjects missing data from one or more entire diaries (i.e., weeks) and had not yet reported opioid cessation by the date of any missing diary were not included in this analysis. | Visits 5-8 (weeks 1-4 post-Total Knee Arthroplasty (TKA)) | 
| Number of Subjects That Experienced at Least One Opioid-Related Side Effect | Throughout the study, subjects were asked if they experienced any side effects related to opioid pain medications. The occurrences of these side effects were recorded and were not considered Adverse Events. The number of subjects that experienced at least one opioid-related side effect at each visit is reported. Baseline is considered Visit 2a (Lead Placement) for Treatment Group subjects and Visit 2b for Control Group subjects. | Baseline (Visit 2a/2b), Visits 4-11 (in-hospital days through 12-months post-Total Knee Arthroplasty (TKA)) | 
| Timed Up and Go (TUG) Test | Subjects began this test from a seated position in a standard chair and were timed while they stood up, walked to a marked point 10 feet away (at a normal, safe pace), returned to the chair, and sat down. Timed Up and Go (TUG) test times are expected to be greater immediately after surgery as compared to baseline. | Visit 1 (Baseline), Visit 4 (In-Hospital), Visit 6 (2-weeks Post-Total Knee Arthroplasty (TKA)), Visit 8 (4-weeks Post-TKA) | 
| Six Minute Walk Test (6MWT) | The total distance that a subject could walk in 6 minutes was recorded, and subjects unable to walk at all were given a score of 0 meters. The median distance was then determined across subjects. 6 Minute Walk Test distances are expected to be reduced immediately after surgery as compared to baseline. | Visit 1 (Baseline), Visit 6 (2-weeks Post-Total Knee Arthroplasty (TKA)), Visit 8 (4-weeks post-TKA) | 
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) | The Western Ontario McMaster University Osteoarthritis Index (WOMAC) questionnaire consists of 24 items that evaluate pain, stiffness, and physical functional disability. Each item is scored on an 11-point numerical rating scale from 0 to 10, where higher scores indicate greater pain, stiffness, and disability. For each subject, the scores from each of the 24 items were summed to calculate the subject's total score, with a minimum score of 0 and a maximum score of 240. The mean total score was then calculated across subjects for each time point. | Visit 1 (Baseline), Visit 3 (Day of Total Knee Arthroplasty (TKA)), Visit 6 (2-weeks post-TKA), Visit 8 (4-weeks post-TKA), Visit 10 (3-months post-TKA), and Visit 11 (12-months post-TKA) | 
| Number of Subjects Reporting Meaningful Improvement, Minimal or No Change, or Meaningful Worsening on the Patient Global Impression of Change (PGIC) Survey | The Patient Global Impression of Change (PGIC) asks subjects to rate their improvement with treatment on a 7-point scale ranging from very much worse to very much improved as compared to before their knee replacement surgery. The subjects combine all the components of their experience into one overall score. Ratings of Much- or Very Much Improved are considered Meaningful Improvements; similarly, ratings of Much- or Very Much Worse are categorized as Meaningfully Worse. Ratings of Minimally Improved, No Change, or Minimally Worse are considered Minimal or No Change. | Visits 3-11 (Day of Total Knee Arthroplasty (TKA) through 12-months post-TKA) | 
| Pain Catastrophizing Scale (PCS) | The Pain Catastrophizing Scale (PCS) questionnaire has 13 questions that assess rumination, magnification, and helplessness. Subjects are asked to think back on painful experiences in the past and reflect on how often they had specific thoughts or feelings. Each of the 13 questions is scored on a 5-point scale where 0 represents not at all, and 4 represents all the time. The scores from each question were summed for each subject to provide a total PCS score, with a possible range from 0 to 52 with higher scores indicating a greater tendency to catastrophize pain (i.e. a higher score indicates a worse outcome). The median scores were then calculated across all subjects. | Visit 1 (Baseline), Visit 8 (4 weeks post-Total Knee Arthroplasty (TKA)), Visit 10 (3-months Post-TKA) | 
| Time to Meet Recovery Milestones up to Twelve Months Post-Total Knee Arthroplasty (TKA) | Participants were queried at each visit from the date of their Total Knee Arthroplasty (TKA) until they met specific, post-surgical recovery milestones. Participants were queried up through the time at which they met each milestone or through their completion of the study, whichever came first (up to twelve months post-surgery). For each milestone, the median number of days between the date of TKA and date to achieve the milestone was calculated. | From Day of Surgery through completion of milestone or 12-months from Day of Surgery, whichever came first | 
| Subject Satisfaction Survey | Subjects completed a sponsor-developed survey with questions pertaining to their feelings about the treatment they received following total knee arthroplasty (TKA) surgery. Treatment Group subjects were asked to report on their experience using the SPRINT Beta Stimulation System as a method for managing post-surgical pain. Depending on the question, subjects were asked to indicate their agreement with the question (strongly disagree, agree, neutral, disagree, strongly disagree), their comfort with the therapy (very uncomfortable, a little bit uncomfortable, fairly comfortable, very comfortable), or when pain relief was felt (immediately, a few minutes later, a few hours later, more than a day later or never). Responses are presented for Treatment Group subjects for key groups of questions related to the therapy whereby answer options are considered affirmative for strongly agree/agree, very easy/easy, very comfortable/comfortable. | Visit 8 (4-weeks post-total knee arthroplasty (TKA)) | 
| Number of Physical Therapy Sessions Attended Following Total Knee Arthroplasty | Following discharge after total knee arthroplasty (TKA) surgery, subjects were asked to report how many physical therapy sessions they attended since the previous study visit. The median number of physical therapy sessions attended is reported for each group at each time point. | Visit 5 (1-week post-Total Knee Arthroplasty (TKA)), Visit 6 (2-weeks post-TKA), Visit 7 (3-weeks post-TKA), Visit 8 (4-weeks post-TKA), Visit 9 (2-months post-TKA), and Visit 10 (3-months post-TKA) | 
| Subject's Use of Device (Compliance) | The hours of usage were recorded for each Lead (femoral and sciatic) from the SPRINT Beta stimulator throughout the study to assess the level of subject compliance with the peripheral nerve stimulation therapy. Treatment Group subjects were asked to use the device for up to 24 hrs each day. The stimulator provided the cumulative number of hours in use since the device was activated. For each timepoint for Treatment Group participants (subjects who received stimulation therapy), the median cumulative number of hours of use for each lead is presented for each timepoint. | Visit 4 (In-Hospital), Visit 6 (2-weeks post-Total Knee Arthroplasty (TKA)), and Visit 8 (4-weeks Post-TKA) | 
| Inpatient Pain Management Experience Survey (Pain Management During Hospital Stay) | Subjects completed a survey comprised of a subset of questions from the Hospital Consumer Assessment of Healthcare Providers and Systems to assess subject satisfaction with pain management during their time in the hospital for total knee arthroplasty surgery. Questions regarding experience with in-hospital pain management are reported below. | 1-week post-Total Knee Arthroplasty (TKA) | 
| Inpatient Pain Management Experience Survey (Pain Medicine During Hospital Stay) | Subjects completed a survey comprised of a subset of questions from the Hospital Consumer Assessment of Healthcare Providers and Systems to assess subject satisfaction with pain management during their time in the hospital for total knee arthroplasty surgery. The number of subjects that responded affirmatively to the following question are reported below: During this hospital stay, did you need medicine for pain? | 1-week post-Total Knee Arthroplasty (TKA) | 
| Inpatient Pain Management Experience Survey (Discharge Facility) | Subjects completed a survey comprised of a subset of questions from the Hospital Consumer Assessment of Healthcare Providers and Systems to assess subject satisfaction with pain management during their time in the hospital for total knee arthroplasty surgery. The question regarding discharge location following hospital stay is reported below. | 1-week post-Total Knee Arthroplasty (TKA) | 
| Inpatient Pain Management Experience Survey (Overall Rating of Hospital) | Subjects completed a survey comprised of a subset of questions from the Hospital Consumer Assessment of Healthcare Providers and Systems to assess subject satisfaction with pain management during their time in the hospital for total knee arthroplasty surgery. As part of this survey, subjects were asked to rate their hospital stay on an 11-point numerical rating scale where 0 represents worst hospital possible and 10 represents best hospital possible. The median score for each group is reported. | 1-week post-Total Knee Arthroplasty (TKA)) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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electrical stimulation, neurostimulation, TKA pain, pain following total knee replacement, total knee arthroplasty