NCT03286543

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

Completed NA Results posted Last updated 12 May 2021

What this trial tests

NA trial testing SPRINT Beta System in Total Knee Replacement in 47 participants. Completed in 15 April 2020.

Timeline

5 September 2017

Primary endpoint
15 April 2020

15 April 2020

Quick facts

Lead sponsor	SPR Therapeutics, Inc.
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	47
Start date	5 September 2017
Primary completion	15 April 2020
Estimated completion	15 April 2020
Sites	5 locations across United States

Drugs / interventions tested

• SPRINT Beta System

Conditions studied

• Total Knee Replacement — all drugs for Total Knee Replacement →
• Total Knee Arthroplasty — all drugs for Total Knee Arthroplasty →
• Pain — all drugs for Pain →
• Postoperative Pain — all drugs for Postoperative Pain →

Sponsor

SPR Therapeutics, Inc.

Who can join

Adults 21 to 90, any sex, with Total Knee Replacement or Total Knee Arthroplasty. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Average Knee Pain While Walking Primary · Postoperative Day 0 to 28 (first 4 weeks following Total Knee Arthroplasty (TKA)

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.

Group	Value	95% CI
Treatment Group	3.70	± 1.97
Control Group	4.14	± 1.49

Number of Subjects That Experienced at Least One Study-Related Adverse Event Primary · 30 months (from when the first Treatment Group subject enrolled to when the last Treatment Group subject completed the study)

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.

Group	Value	95% CI
Treatment Group	8

Average Knee Pain Over the Last 24 Hours Secondary · Postoperative Day 0 to 28 (first 4 weeks following Total Knee Arthroplasty (TKA))

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.

Group	Value	95% CI
Treatment Group	3.24	± 1.52
Control Group	4.32	± 1.34

Average Knee Pain at Rest Secondary · Postoperative Day 0 to 28 (first 4 weeks following Total Knee Arthroplasty (TKA))

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.

Group	Value	95% CI
Treatment Group	2.86	± 1.23
Control Group	3.48	± 1.33

Pain Right Now as Measured by the Brief Pain Inventory Secondary · 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)

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

Group	Value	95% CI
Treatment Group	1.0	0 – 2
Control Group	3.0	1 – 10

Visit 3 (Day of TKA)

Group	Value	95% CI
Treatment Group	2.0	0 – 8
Control Group	2.0	0 – 10

Visit 4 (In-Hospital)

Group	Value	95% CI
Treatment Group	2.0	1 – 6
Control Group	3.5	0 – 7

Visit 6 (2-weeks Post-TKA)

Group	Value	95% CI
Treatment Group	2.0	1 – 8
Control Group	3.0	0 – 6

Visit 8 (4-weeks Post-TKA)

Group	Value	95% CI
Treatment Group	1.0	0 – 3
Control Group	1.0	0 – 6

Amount of Analgesic Usage Secondary · Visits 5-8 (weeks 1-4 post-Total Knee Arthroplasty (TKA))

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 no

Visit 5 (1-week Post-TKA)

Group	Value	95% CI
Treatment Group	29.9	3.2 – 49.3
Control Group	31.4	0.0 – 107.1

Visit 6 (2-weeks Post-TKA)

Group	Value	95% CI
Treatment Group	21.4	2.1 – 31.1
Control Group	22.5	0.0 – 88.8

Visit 7 (3-weeks Post-TKA)

Group	Value	95% CI
Treatment Group	13.6	1.1 – 20.0
Control Group	17.1	0.0 – 69.6

Visit 8 (4-weeks Post-TKA)

Group	Value	95% CI
Treatment Group	11.4	0.0 – 20.7
Control Group	2.9	0.0 – 47.1

Average Across Visits 5-8

Group	Value	95% CI
Treatment Group	19.1	2.1 – 26.8
Control Group	16.8	0.13 – 75.0

Number of Subjects That Experienced at Least One Opioid-Related Side Effect Secondary · Baseline (Visit 2a/2b), Visits 4-11 (in-hospital days through 12-months post-Total Knee Arthroplasty (TKA))

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

Group	Value	95% CI
Treatment Group	0
Control Group	0

Visit 4 (In-Hospital)

Group	Value	95% CI
Treatment Group	3
Control Group	7

Visit 5 (1-week Post-TKA)

Group	Value	95% CI
Treatment Group	3
Control Group	9

Visit 6 (2-weeks Post-TKA)

Group	Value	95% CI
Treatment Group	3
Control Group	8

Visit 7 (3-weeks Post-TKA)

Group	Value	95% CI
Treatment Group	2
Control Group	6

Visit 8 (4-weeks Post-TKA)

Group	Value	95% CI
Treatment Group	1
Control Group	4

Visit 9 (2-months Post-TKA)

Group	Value	95% CI
Treatment Group	0
Control Group	0

Visit 10 (3-months Post-TKA)

Group	Value	95% CI
Treatment Group	0
Control Group	0

Timed Up and Go (TUG) Test Secondary · Visit 1 (Baseline), Visit 4 (In-Hospital), Visit 6 (2-weeks Post-Total Knee Arthroplasty (TKA)), Visit 8 (4-weeks Post-TKA)

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.

Time at Visit 1 (Baseline)

Group	Value	95% CI
Treatment Group	12.44	4.82 – 13.7
Control Group	10.25	7 – 26.24

Time at Visit 4 (In-Hospital)

Group	Value	95% CI
Treatment Group	41.80	11.13 – 141.32
Control Group	42.22	13.81 – 82.37

Time at Visit 6 (2-weeks Post-TKA)

Group	Value	95% CI
Treatment Group	14.28	7.63 – 32.36
Control Group	15.93	7.39 – 56.0

Time at Visit 8 (4-weeks Post-TKA)

Group	Value	95% CI
Treatment Group	10.68	6.59 – 17.07
Control Group	10.38	6.9 – 40.68

Six Minute Walk Test (6MWT) Secondary · Visit 1 (Baseline), Visit 6 (2-weeks Post-Total Knee Arthroplasty (TKA)), Visit 8 (4-weeks post-TKA)

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)

Group	Value	95% CI
Treatment Group	458.5	320.0 – 555.0
Control Group	351.3	0 – 504.0

Visit 6 (2-weeks Post-TKA)

Group	Value	95% CI
Treatment Group	280.0	150.0 – 504.7
Control Group	281.0	0 – 680.2

Visit 8 (4-weeks Post-TKA)

Group	Value	95% CI
Treatment Group	410.0	270.0 – 693.0
Control Group	329.0	0 – 518.9

Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Secondary · 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)

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)

Group	Value	95% CI
Treatment Group	87.00	± 30.34
Control Group	111.31	± 38.78

Visit 3 (Day of TKA)

Group	Value	95% CI
Treatment Group	68.71	± 47.87
Control Group	99.23	± 51.25

Visit 6 (2-weeks Post-TKA)

Group	Value	95% CI
Treatment Group	58.57	± 33.24
Control Group	81.13	± 38.98

Visit 8 (4-weeks Post-TKA)

Group	Value	95% CI
Treatment Group	40.29	± 26.56
Control Group	51.94	± 30.83

Visit 10 (3-months Post-TKA)

Group	Value	95% CI
Treatment Group	22.86	± 22.13
Control Group	29.38	± 21.05

Visit 11 (12-months Post-TKA)

Group	Value	95% CI
Treatment Group	4.83	± 4.36
Control Group	12.79	± 20

Number of Subjects Reporting Meaningful Improvement, Minimal or No Change, or Meaningful Worsening on the Patient Global Impression of Change (PGIC) Survey Secondary · Visits 3-11 (Day of Total Knee Arthroplasty (TKA) through 12-months post-TKA)

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."

Visit 3 (Day of TKA)

Group	Value	95% CI
Treatment Group	0
Control Group	1
Treatment Group	5
Control Group	14
Treatment Group	2
Control Group	1

Visit 4 (In-Hospital)

Group	Value	95% CI
Treatment Group	1
Control Group	4
Treatment Group	5
Control Group	9
Treatment Group	1
Control Group	2

Visit 5 (1-week Post-TKA)

Group	Value	95% CI
Treatment Group	2
Control Group	3
Treatment Group	3
Control Group	11
Treatment Group	2
Control Group	2

Visit 6 (2-weeks Post-TKA)

Group	Value	95% CI
Treatment Group	2
Control Group	3
Treatment Group	3
Control Group	11
Treatment Group	2
Control Group	1

Visit 7 (3-weeks Post-TKA)

Group	Value	95% CI
Treatment Group	2
Control Group	3
Treatment Group	3
Control Group	12
Treatment Group	2
Control Group	1

Visit 8 (4-weeks Post-TKA)

Group	Value	95% CI
Treatment Group	2
Control Group	6
Treatment Group	3
Control Group	9
Treatment Group	2
Control Group	1

Visit 9 (2-months Post-TKA)

Group	Value	95% CI
Treatment Group	4
Control Group	8
Treatment Group	3
Control Group	7
Treatment Group	0
Control Group	0

Visit 10 (3-months Post-TKA)

Group	Value	95% CI
Treatment Group	6
Control Group	9
Treatment Group	1
Control Group	4
Treatment Group	0
Control Group	0

Pain Catastrophizing Scale (PCS) Secondary · Visit 1 (Baseline), Visit 8 (4 weeks post-Total Knee Arthroplasty (TKA)), Visit 10 (3-months Post-TKA)

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 indica

Visit 1 (Baseline)

Group	Value	95% CI
Treatment Group	7	0 – 13
Control Group	7	0 – 34

Visit 8 (4-weeks Post-TKA)

Group	Value	95% CI
Treatment Group	6	0 – 14
Control Group	4	0 – 19

Visit 10 (3-months Post-TKA)

Group	Value	95% CI
Treatment Group	1	0 – 13
Control Group	0	0 – 15

Adverse events — posted to ClinicalTrials.gov

Time frame: Each participant enrolled was assessed for adverse events from the time of informed consent through the 12-month follow up visit. The total assessment period was approximately 13 months for each participant.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment Group

Serious: 2/18 (11%)

Deaths: 0/18

Control Group

Serious: 3/23 (13%)

Deaths: 0/23

Serious adverse events (6 terms)

Reaction	System	Treatment Group	Control Group
Prostate Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Acute Myopericarditis	Cardiac disorders	—	—
Pain at TKA Surgical Site	Musculoskeletal and connective tissue disorders	—	—
Adverse Drug Reaction During TKA	Surgical and medical procedures	—	—
Acute Pancreatitis and Gall Stones	Gastrointestinal disorders	—	—
Sepsis due to Urinary Tract Infection	Infections and infestations	—	—

Other adverse events (29 terms — click to expand)

Reaction	System	Treatment Group	Control Group
Skin irritation or bruising at pad and/or Lead exit site	Skin and subcutaneous tissue disorders	—	—
Illness	General disorders	—	—
Skin irritation at bandage site	Skin and subcutaneous tissue disorders	—	—
Generalized itching	Skin and subcutaneous tissue disorders	—	—
Discharge from TKA surgical incision	Skin and subcutaneous tissue disorders	—	—
Burning sensation and swelling of knee	Skin and subcutaneous tissue disorders	—	—
Ulcers	Skin and subcutaneous tissue disorders	—	—
Wound dehiscence	Skin and subcutaneous tissue disorders	—	—
New hip pain	Musculoskeletal and connective tissue disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Pain at TKA surgical site	Musculoskeletal and connective tissue disorders	—	—
Worsening knee pain	Musculoskeletal and connective tissue disorders	—	—
Ankylosis of knee	Musculoskeletal and connective tissue disorders	—	—
Knee effusion	Musculoskeletal and connective tissue disorders	—	—
Muscle spasming	Musculoskeletal and connective tissue disorders	—	—
Sciatica and Piriformis Syndrome	Musculoskeletal and connective tissue disorders	—	—
Thumb pain	Musculoskeletal and connective tissue disorders	—	—
Shoulder pain	Musculoskeletal and connective tissue disorders	—	—
Worsening cataract	Eye disorders	—	—
Elevated blood pressure	Cardiac disorders	—	—
Urinary tract infection	Renal and urinary disorders	—	—
Bronchial asthma	Respiratory, thoracic and mediastinal disorders	—	—
Bronchitis	Respiratory, thoracic and mediastinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Hearing loss	Ear and labyrinth disorders	—	—
Soreness after Lead placement	Product Issues	—	—
Shocking at Lead site	Product Issues	—	—
Restless Leg Syndrome flare up	Nervous system disorders	—	—

Most-reported serious reactions: Prostate Cancer, Acute Myopericarditis, Pain at TKA Surgical Site, Adverse Drug Reaction During TKA, Acute Pancreatitis and Gall Stones, Sepsis due to Urinary Tract Infection.

Data from ClinicalTrials.gov NCT03286543 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Peripheral nerve stimulation for chronic knee pain following total knee arthroplasty: a systematic review.
   Amirianfar E, Rosales R, Logan A, Doshi TL, et al · · 2023 · cited 4× · PMID 37937468 · DOI 10.2217/pmt-2023-0057