NCT03481725

Ultrasound-Guided Percutaneous Peripheral Nerve Stimulation: A Department of Defense Funded Multicenter Pilot Study

Completed NA Results posted Last updated 18 March 2021

What this trial tests

NA trial testing ACTIVE peripheral nerve stimulation with a percutaneously inserted lead and wearable stimulator (SPR Therapeutics, Cleveland, Ohio) in Rotator Cuff Repair in 65 participants. Completed in 7 January 2021.

Timeline

14 July 2018

Primary endpoint
11 September 2020

7 January 2021

Quick facts

Lead sponsor	University of California, San Diego
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	65
Start date	14 July 2018
Primary completion	11 September 2020
Estimated completion	7 January 2021
Sites	6 locations across United States

Drugs / interventions tested

• ACTIVE peripheral nerve stimulation with a percutaneously inserted lead and wearable stimulator (SPR Therapeutics, Cleveland, Ohio)
• SHAM peripheral nerve stimulation with a percutaneously inserted lead and wearable SHAM stimulator (SPR Therapeutics, Cleveland, Ohio)

Conditions studied

• Rotator Cuff Repair — all drugs for Rotator Cuff Repair →
• Anterior Cruciate Ligament Reconstruction — all drugs for Anterior Cruciate Ligament Reconstruction →
• Ankle Arthrodesis or Arthroplasty — all drugs for Ankle Arthrodesis or Arthroplasty →
• Hallux Valgus Correction — all drugs for Hallux Valgus Correction →

Sponsor

University of California, San Diego

Who can join

18 and older, any sex, with Rotator Cuff Repair or Anterior Cruciate Ligament Reconstruction. 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.

Opioid Consumption During First Postoperative Week Primary · Postoperative days 0-7

Cumulative opioid dose from days 0-7, collected on days 0, 1, 2, 3, 4, and 7 for the previous 24 hours at each time point measured in morphine equivalents

Group	Value	95% CI
Peripheral Nerve Stimulation	5.0	0 – 30.0
Sham	47.5	25 – 90

Average Pain During First Postoperative Week Primary · Postoperative days 0-7

Mean value of the "average" pain scores measured using the numeric rating scale, collected on days 0, 1, 2, 3, 4, and 7 for the previous 24 hours at each time point. This is a 0-10 Likert scale measuring pain level with 0 = no pain and 10 = worst imaginable pain

Group	Value	95% CI
Peripheral Nerve Stimulation	1.1	± 1.1
Sham	3.1	± 1.7

Opioid Consumption Individual Time Points Secondary · Postoperative days 1, 2, 3, 4, 7, 11, and 15; as well as Months 1 and 4

Cumulative opioid dose of previous 24 hours (measured in morphine equivalents)

Postoperative Day 1

Group	Value	95% CI
Peripheral Nerve Stimulation	0	0 – 100
Sham	15	0 – 20

Postoperative Day 2

Group	Value	95% CI
Peripheral Nerve Stimulation	5	0 – 10
Sham	20	10 – 30

Postoperative Day 3

Group	Value	95% CI
Peripheral Nerve Stimulation	0	0 – 0
Sham	10	0 – 20

Postoperative Day 4

Group	Value	95% CI
Peripheral Nerve Stimulation	0	0 – 0
Sham	5	0 – 20

Postoperative Day 7

Group	Value	95% CI
Peripheral Nerve Stimulation	0	0 – 0
Sham	0	0 – 10

Postoperative Day 11

Group	Value	95% CI
Peripheral Nerve Stimulation	0	0 – 0
Sham	0	0 – 5

Postoperative Day 15

Group	Value	95% CI
Peripheral Nerve Stimulation	0	0 – 0
Sham	0	0 – 0

Postoperative Month 1

Group	Value	95% CI
Peripheral Nerve Stimulation	0	0 – 0
Sham	0	0 – 0

Brief Pain Inventory, Short Form (Interference Domain) Secondary · Postoperative days 3, and 7; as well as Months 1 and 4

The Brief Pain Inventory (short form) interference domain is comprised of 7 questions involving physical and emotional functioning using a 0-10 Likert scale \[0 = no interference; 10 = complete interference\]: general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. The score is calculated by adding the responses for each individual question resulting in a possible range of 0-70 (higher = worse).

Postoperative Day 3

Group	Value	95% CI
Peripheral Nerve Stimulation	2.6	± 4.5
Sham	21.5	± 17.9

Postoperative Day 7

Group	Value	95% CI
Peripheral Nerve Stimulation	2.5	± 4.9
Sham	19.0	± 17.0

Postoperative Month 1

Group	Value	95% CI
Peripheral Nerve Stimulation	4.0	± 7.7
Sham	6.2	± 10.4

Postoperative Month 4

Group	Value	95% CI
Peripheral Nerve Stimulation	1.6	± 3.7
Sham	5.8	± 12.3

Average Pain at Individual Time Points Secondary · Postoperative days 1, 2, 3, 4, 7, 11, and 15; as well as Months 1 and 4

Mean of the "average" pain scores of previous 24 hours measured on a 0-10 Numeric Rating Scale with 0=no pain and 10=worst imaginable pain

Postoperative Day 1

Group	Value	95% CI
Peripheral Nerve Stimulation	1.8	± 1.8
Sham	4.0	± 2.6

Postoperative Day 2

Group	Value	95% CI
Peripheral Nerve Stimulation	1.3	± 1.4
Sham	3.9	± 2.1

Postoperative Day 3

Group	Value	95% CI
Peripheral Nerve Stimulation	0.9	± 1.2
Sham	3.1	± 2.3

Postoperative Day 4

Group	Value	95% CI
Peripheral Nerve Stimulation	0.7	± 1.2
Sham	2.3	± 2.0

Postoperative Day 7

Group	Value	95% CI
Peripheral Nerve Stimulation	0.6	± 1.1
Sham	1.9	± 2.1

Postoperative Day 11

Group	Value	95% CI
Peripheral Nerve Stimulation	0.3	± 0.2
Sham	1.7	± 1.4

Postoperative Day 15

Group	Value	95% CI
Peripheral Nerve Stimulation	0.9	± 0.6
Sham	1.9	± 1.6

Postoperative Month 1

Group	Value	95% CI
Peripheral Nerve Stimulation	0.5	± 0.8
Sham	1.3	± 1.8

Worst Pain at Individual Time Points Secondary · Postoperative days 1, 2, 3, 4, 7, 11, and 15; as well as Months 1 and 4

Median of the worst pain scores of previous 24 hours measured on a 0-10 Numeric Rating Scale with 0=no pain and 10=worst imaginable pain

Postoperative Day 1

Group	Value	95% CI
Peripheral Nerve Stimulation	4	0 – 6
Sham	7.8	3 – 9

Postoperative Day 2

Group	Value	95% CI
Peripheral Nerve Stimulation	4	2 – 6
Sham	7.5	5 – 9

Postoperative Day 3

Group	Value	95% CI
Peripheral Nerve Stimulation	3	0 – 4
Sham	6	4 – 8

Postoperative Day 4

Group	Value	95% CI
Peripheral Nerve Stimulation	1.3	0 – 4
Sham	4.3	3 – 7

Postoperative Day 7

Group	Value	95% CI
Peripheral Nerve Stimulation	1.8	0 – 3.5
Sham	3.5	3 – 5

Postoperative Day 11

Group	Value	95% CI
Peripheral Nerve Stimulation	0.5	0 – 2
Sham	3	1 – 5

Postoperative Day 15

Group	Value	95% CI
Peripheral Nerve Stimulation	1.0	0 – 5
Sham	2	0 – 4.5

Postoperative Month 1

Group	Value	95% CI
Peripheral Nerve Stimulation	3.0	0 – 4
Sham	2	0 – 4

Least Pain at Individual Time Points Secondary · Postoperative days 3 and 7; as well as Months 1 and 4

Least pain scores of previous 24 hours measured on a 0-10 Numeric Rating Scale with 0=no pain and 10=worst imaginable pain. Participants were asked "what was the lowest pain within the last 24 hours measured using the 0 to 10 scale, with 0 equal to no pain and 10 equal to the worst imaginable pain"?

Postoperative Day 3

Group	Value	95% CI
Peripheral Nerve Stimulation	0.2	± 0.6
Sham	1.4	± 1.8

Postoperative Day 7

Group	Value	95% CI
Peripheral Nerve Stimulation	0.2	± 0.7
Sham	0.7	± 1.6

Postoperative Month 1

Group	Value	95% CI
Peripheral Nerve Stimulation	0.1	± 0.3
Sham	0.5	± 1.0

Postoperative Month 4

Group	Value	95% CI
Peripheral Nerve Stimulation	0.3	± 0.2
Sham	0.4	± 1.2

Current Pain at Individual Time Points Secondary · Postoperative days 3 and 7; as well as Months 1 and 4

Current pain scores at the time of the data-collection phone call measured on a 0-10 Numeric Rating Scale with 0=no pain and 10=worst imaginable pain

Postoperative Day 3

Group	Value	95% CI
Peripheral Nerve Stimulation	0.4	± 0.7
Sham	2.3	± 2.3

Postoperative Day 7

Group	Value	95% CI
Peripheral Nerve Stimulation	0.3	± 0.8
Sham	1.5	± 2.2

Postoperative Month 1

Group	Value	95% CI
Peripheral Nerve Stimulation	0.3	± 0.8
Sham	1.0	± 1.8

Postoperative Month 4

Group	Value	95% CI
Peripheral Nerve Stimulation	0.1	± 0.6
Sham	0.4	± 0.9

Defense and Veterans Pain Rating Score Secondary · Postoperative days 3, and 7; as well as Months 1 and 4

Instrument designed to assess pain level specifically for active duty military and Veteran patient populations. It is a Likert scale from 0 (no pain) to 10 (worst imaginable pain).

Postoperative Day 3

Group	Value	95% CI
Peripheral Nerve Stimulation	1.4	± 1.5
Sham	4.2	± 2.3

Postoperative Day 7

Group	Value	95% CI
Peripheral Nerve Stimulation	1.1	± 1.5
Sham	2.9	± 2.5

Postoperative Month 1

Group	Value	95% CI
Peripheral Nerve Stimulation	1.3	± 1.4
Sham	1.5	± 2.0

Postoperative Month 4

Group	Value	95% CI
Peripheral Nerve Stimulation	0.6	± 1.4
Sham	1.2	± 1.7

Adverse events — posted to ClinicalTrials.gov

Time frame: 4 months following surgery. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Peripheral Nerve Stimulation

Serious: 0/31 (0%)

Deaths: 0/31

Sham

Serious: 0/34 (0%)

Deaths: 0/34

Other adverse events (2 terms — click to expand)

Reaction	System	Peripheral Nerve Stimulation	Sham
Lead fracture during purposeful removal	Musculoskeletal and connective tissue disorders	—	—
Adhesive reaction	Musculoskeletal and connective tissue disorders	—	—

Data from ClinicalTrials.gov NCT03481725 adverse events section.

Sponsor's own description

Postoperative pain is usually treated with opioids that have undesirable and sometimes dangerous side effects (e.g., vomiting and respiratory depression)-and yet over 80% of patients still experience inadequate pain relief. A novel, non-pharmacologic analgesic technique-percutaneous peripheral nerve stimulation (PNS)- holds extraordinary potential to greatly reduce or obviate opioid requirements and concurrently improve analgesia following painful surgery. This technique involves inserting an insulated electric lead adjacent to a target nerve through a needle prior to surgery using ultrasound guidance. Following surgery, a tiny electric current is delivered to the nerve resulting in potent pain control without any cognitive or adverse systemic side effects whatsoever. The electrical pulse generator (stimulator) is so small it is simply affixed to the patient's skin. The leads are already cleared by the US Food and Drug Administration to treat acute (postoperative) pain for up to 60 days; and, since percutaneous PNS may be provided on an outpatient basis, the technique holds the promise of providing potent analgesia outlasting the pain of surgery-in other words, the possibility of a painless, opioid-free recovery following surgery.

The current project is a multicenter, randomized, double-masked, placebo-controlled, parallel-arm clinical pilot study to (1) determine the feasibility and optimize the protocol of a planned definitive clinical trial; and (2) estimate the treatment effect of percutaneous PNS on pain and opioid consumption following moderate-to-severely painful ambulatory surgery compared with usual and customary opioid-based analgesia. This will allow determination of the required sample size for a subsequent definitive multicenter clinical trial. Combined, the pilot study and definitive trial have a strong potential to dramatically reduce or obviate postoperative opioid requirements and their resultant negative effects on both individuals and society; while concurrently improving analgesia, increasing the ability to function in daily life, decreasing the risk of transition from acute to chronic pain, and improving quality of life.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Percutaneous Peripheral Nerve Stimulation (Neuromodulation) for Postoperative Pain: A Randomized, Sham-controlled Pilot Study.
   Ilfeld BM, Plunkett A, Vijjeswarapu AM, Hackworth R, et al · · 2021 · cited 67× · PMID 33856424 · DOI 10.1097/aln.0000000000003776
2. Ultrasound-Guided Percutaneous Peripheral Nerve Stimulation: A Pragmatic Effectiveness Trial of a Nonpharmacologic Alternative for the Treatment of Postoperative Pain.
   Ilfeld BM, Gelfand H, Dhanjal S, Hackworth R, et al · · 2020 · cited 12× · PMID 33313729 · DOI 10.1093/pm/pnaa332
3. Emerging Nonpharmacologic Analgesic Technologies in Anesthesia: Mechanisms, Evidence, and Future Directions for Pharmacologic Alternatives.
   McKenzie A, Dombrower R, McKenzie S, Theeraphapphong N, et al · · 2026 · PMID 41595760 · DOI 10.3390/biomedicines14010225