Clinical Data
iovera° Clinical Studies
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

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
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

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
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

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
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

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
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

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
Additional Publications
REFERENCES
- 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.
- Mihalko WM et al. J Arthroplasty. 2021;36(5):1590-1598.
- Plessl D et al. J Am Acad Orthop Surg. 2020;28(21):e962-e968
- 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.
- Urban JA et al. Arthroplasty Today. 2021; 10:87-92
- Gabriel RA, Ilfeld BM. Novel methodologies in regional anesthesia for knee arthroplasty. Anesthesiol Clin. 2018;36(3):387-401.
- 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.
- 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.
- Hsu M, Stevenson FF. Wallerian degeneration and recovery of motor nerves after multiple focused cold therapies. Muscle Nerve. 2015;51(2):268-275.
- 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.