Clinical Data

iovera° Clinical Studies

Retrospective total knee arthroplasty (TKA) study1

Retrospective total knee arthroplasty (TKA) study1

Study Overview

  • Single site (Louisiana State University Health Sciences Center School of Medicine); retrospective review; N=100
  • Treatment group = First 50 patients treated after iovera° introduced
  • Control group = Last 50 patients treated before iovera° introduced

Methods

  • iovera° treatment of the infrapatellar branch of the saphenous
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Results

  • The iovera° group required 45% less opioids during the 12 weeks after surgery, based on prescription requests
  • Compared with the control group, the iovera° group demonstrated a significantly greater improvement in KOOS symptom scores at 6 weeks and 12 weeks
  • The iovera° group demonstrated within-group significant reductions in PROMIS® pain intensity and pain interference at 2- and 6-week follow-up, respectively (P<0.0001)
  • The most common side effect was local bruising at the site of treatment

KOOS=Knee Injury and Osteoarthritis Outcome Score;

PROMIS=Patient-Reported Outcomes Measurement Information System.

*P value not reported

Percutaneous freezing of sensory nerves prior to total knee arthroplasty

Read the Full Study from the Knee Journal

Prospective randomized TKA clinical study2

Study Overview

  • Single site (Campbell Clinic)
  • Prospective (N=124)
  • 2 hospitals, 5 surgeons
  • Randomized 1:1

Methods

  • Control group=standard of care TKA
  • Treatment group=iovera° 3 to 7 days prior to TKA
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Results

  • Results for the iovera° group demonstrated both a reduction in opioid use and an improvement in KOOS symptom score with a per-protocol analysis, but not with an intent to treat analysis.
  • Compared with the control group, a per protocol analysis showed the iovera° treatment group demonstrated significantly
    • Lower opioid consumption at 72 hours, 6 weeks, and 12 weeks after discharge
    • More opioid-free patients at 6 weeks after discharge
    • Reduced KOOS scores from baseline to each follow-up assessment
  • 34% less opioids were required 6 weeks after discharge (mean, 4.2 mg vs 5.9 mg; P=0.0186).

KOOS=Knee Injury and Osteoarthritis Outcome Score

Cryoneurolysis before total knee arthroplasty in patients with severe osteoarthritis for reduction of postoperative pain and opioid use in a single-center randomized controlled trial

Read the Full Study from The Journal of Arthroplasty

Retrospective total knee arthroplasty (TKA) study3

Study Overview

  • Retrospective, single center study
  • N=323; Standard recovery protocol (SRP)=129; Rapid recovery protocol (RRP)=194

Methods

  • Single orthopedic surgeon
  • Primary TKA
  • Knee ROM assessed at perioperative visit and scheduled postoperative visits for up to 1 year
  • Differences in mean LOS between groups were compared using Poisson regression with and without adjustment for covariates
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Results

  • Compared with SRP, an RRP reduces the LOS, facilitating faster attainment of clinically meaningful recovery of knee ROM in patients undergoing a primary TKA
  • All patients, regardless of recovery protocol type, experienced the largest improvement in flexion and flexion contrcture during first 12 weeks after surgery

ROM=range of motion; LOS=length of stay

Rapid versus standard recovery protocol is associated with improved recovery of range of motion 12 weeks after total knee arthroplasty

Read the Full Study from AAOS

Prospective knee osteoarthritis (OA) study4

Study Overview

  • Multicenter, prospective, sham-controlled, double-blind study
  • 17 sites across the United States; N=180 (randomized 2:1)
  • Treatment group = 121 subjects treated with iovera°
  • Control group = 59 subjects treated with a sham tip

Methods

  • Treatment of the ISN only
  • Patients were followed through to 120 days
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Results

  • The iovera° group demonstrated a significantly greater reduction in WOMAC pain score at Days 30, 60, and 90 (P<0.02)
  • The most common side effects were bruising, numbness, redness, tenderness upon palpation, and swelling

WOMAC=Western Ontario and McMaster Osteoarthritis Index

Cryoneurolysis to treat the pain and symptoms of knee osteoarthritis; a multicenter, randomized, double-blind, sham-controlled trial

Read the Full Study from OARSI

Retrospective total knee arthroplasty (TKA) study5

Study Overview

  • Single-site retrospective chart review of patients (N=267) undergoing an inpatient primary TKA
  • Treatment group = 169 subjects treated with iovera°
  • Control group = 98 subjects underwent TKA without cryoneurolysis

Methods

  • Both groups received similar perioperative multimodal pain management protocols
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Results

  • The iovera° group demonstrated a 51% lower adjusted mean daily opioid consumption and a 68% reduction in total adjusted mean opioid consumption vs. control
  • The iovera° group showed more significant knee flexion and extension at discharge and a significant reduction in overall hospital length of stay
  • The most common side effects were numbness in the area of treated nerves and dysesthesia that was tolerable without disruption of activities

A multimodal pain management protocol including preoperative cryoneurolysis for total knee arthroplasty to reduce pain, opioid consumption, and length of stay

Read the Full Study from Arthroplasty Today

Additional Publications

Publication Summaries

Novel methodologies in regional anesthesia for knee arthroplasty. Gabriel RA, et al. Anesthesiology Clinics. 2018.
Although a single application of ultrasound-guided percutaneous cryoneurolysis provides weeks to months of analgesia, careful selection of candidates is required.6
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Publication Summaries

Ultrasound-guided percutaneous cryoneurolysis for treatment of acute pain: could cryoanalgesia replace continuous peripheral nerve blocks? Ilfeld BM, et al. British Journal of Anaesthesia. 2017.
Concludes that “current evidence suggests that ultrasound-guided percutaneous cryoanalgesia holds enormous potential for making a dramatic leap forward in providing long-term analgesia, far surpassing typical continuous peripheral nerve blocks, with minimal risk and a lower patient burden.”7
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Publication Summaries

Novel cryoneurolysis device for the treatment of sensory and motor peripheral nerves. Ilfeld BM, et al. Expert Review of Medical Devices. 2016.
Concludes that “changes in the US healthcare system such as a push for the reduction of opioid use and the incorporation of Diagnostic Related Group codes, as well as recent technological advances including a handheld unit that allows for treatment of superficial nerves while protecting the skin from damage, may contribute to the resurgence of cryoneurolysis for the treatment of peripheral nerves.”8
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Publication Summaries

Wallerian degeneration and recovery of motor nerves after multiple focused cold therapies. Hsu M, et al. Muscle & Nerve. 2015.
There was consistent weakening of physiological function and restoration of normal function after each treatment. Low-temperature treatment of motor nerves did not result in permanent or long-term changes to nerve function or structure.9
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Publication Summaries

Reduction in muscular motility by selective focused cold therapy: a preclinical study. Hsu M, et al. Journal of Neural Transmission. 2014.
Application of low temperatures to peripheral motor nerves resulted in temporary denervation and loss of function of the treated rat hind limb. Low-temperature treatment on motor nerves did not result in any permanent or long-term changes to function and structure of the nerves.10
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REFERENCES

  1. Dasa V, Lensing G, Parsons M, Harris J, Volaufova J, Bliss R. Percutaneous freezing of sensory nerves prior to total knee arthroplasty. Knee. 2016;23(3):523-528.
  2. Mihalko WM et al. J Arthroplasty. 2021;36(5):1590-1598.
  3. Plessl D et al. J Am Acad Orthop Surg. 2020;28(21):e962-e968
  4. Radnovich R, Scott D, Patel AT, et al. Cryoneurolysis to treat the pain and symptoms of knee osteoarthritis: a multicenter, randomized, double-blind, sham-controlled trial. Osteoarthritis Cartilage. 2017;25(8):1247-1256.
  5. Urban JA et al. Arthroplasty Today. 2021; 10:87-92
  6. Gabriel RA, Ilfeld BM. Novel methodologies in regional anesthesia for knee arthroplasty. Anesthesiol Clin. 2018;36(3):387-401.
  7. Ilfeld BM, Gabriel RA, Trescot AM. Ultrasound-guided percutaneous cryoneurolysis for treatment of acute pain: could cryoanalgesia replace continuous peripheral nerve blocks? Br J Anaesth. 2017;119(4):703-706.
  8. Ilfeld BM, Preciado J, Trescot AM. Novel cryoneurolysis device for the treatment of sensory and motor peripheral nerves. Expert Rev Med Devices. 2016;13(8):713-725.
  9. Hsu M, Stevenson FF. Wallerian degeneration and recovery of motor nerves after multiple focused cold therapies. Muscle Nerve. 2015;51(2):268-275.
  10. Hsu M, Stevenson FF. Reduction in muscular motility by selective focused cold therapy: a preclinical study. J Neural Transm (Vienna). 2014;121(1):15-20.

IndicationThe iovera° system is used to destroy tissue during surgical procedures by applying freezing cold. It can also be used to produce lesions in peripheral nervous tissue by the application of cold to the selected site for the blocking of pain. It is also indicated for the relief of pain and symptoms associated with osteoarthritis of the knee for up to 90 days. The iovera° system is not indicated for treatment of central nervous system tissue. The iovera° system's "1x90" Smart Tip configuration (indicating one needle which is 90mm long) can also facilitate target nerve location by conducting electrical nerve stimulation from a separate nerve simulator.

Important Safety Information

ContraindicationsThe iovera° system is contraindicated for use in patients with the following:

  • Cryoglobulinemia, paroxysmal cold hemoglobinuria, cold urticaria, Raynaud’s disease, and open and/or infected wounds at or near the treatment site

Potential ComplicationsAs with any surgical treatment that uses needle-based therapy and local anesthesia, there is a potential for site-specific reactions, including, but not limited to:

  • Ecchymosis, edema, erythema, local pain and/or tenderness, and localized dysesthesia

Proper use of the device as described in the User Guide can help reduce or prevent the following complications:

  • At the treatment site(s): injury to the skin related to application of cold or heat, hyper- or hypopigmentation, and skin dimpling
  • Outside the treatment site(s): loss of motor function