iovera° Clinical data summary

The clinical value of iovera has been established in two high unmet need settings of knee osteoarthritis and total knee arthroplasty, respectively.

Prospective knee osteoarthritis (OA) study

Study overview1

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

Methods1

  • Treatment of the infrapatellar branch of the saphenous nerve (ISN) only
  • Patients were followed through 120 days post-treatment

Results1

The primary endpoint was the least squares (LS) mean change from baseline (average of the mean changes from baseline) to Day 30 in WOMAC pain subscale score. The iovera° group demonstrated a statistically significant greater change from baseline in the WOMAC Total score than the sham group at Days 30 (P=0.0010) and 90 (P=0.0108)
The most common side effects were bruising, numbness, redness, tenderness upon palpation and swelling.


Reported P value is vs control group.


Retrospective total knee arthroplasty (TKA) study

Study overview2

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

Methods2

The treatment group (cryoneurolysis plus multimodal pain management) received cryoneurolysis of the AFCN and ISN five days prior to surgery in addition to the standard preoperative multimodal pain management program.

Results for the iovera° group2

  • Required 45% less opioids than the control group during the 12 weeks after surgery based on prescription requests P<0.0001
  • Compared to the control group, the iovera° treatment group demonstrated significantly greater improvement in knee injury and osteoarthritis outcome score (KOOS) symptoms scores at 6 weeks and 12 weeks post surgery
  • 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)
  • Significantly fewer iovera° patients (6%) had a length of stay of ≥2 days compared with the control group (67%), P<0.0001
  • The most common side effect was local bruising at the site of treatment


Prospective total knee arthroplasty (TKA) study

Study overview3

  • A prospective, randomized, unblinded, controlled trial; N=124
  • Treatment Group = ITT: 62 subjects (PP: 48) treated with iovera°
  • Control Group = ITT: 62 subjects (PP: 48) treated with current preoperative standard of care (SOC)

Methods3

  • iovera° treatment was focused on freezing the superficial genicular nerves, more specifically referred to as the ISN and the AFCN
  • The SOC group could receive local infiltration analgesia (periarticular and posterior capsule; 1% lidocaine along the two lines of treatment, with 5cc administered along each treatment line) during surgery.

Results3

  • The primary end point* was not met in the ITT analysis (4.8 control group vs 6.1 mg SOC; P = 0.0841) but was met in the PP analysis (4.2 vs 5.9 mg; P = 0.0186) after excluding patients with medication deviations or missing follow-up data.
  • Compared with the SOC group, the iovera° group had improved functional scores and numerical improvements in pain scores across all follow-up assessments, with significant improvements observed in current pain from baseline to the 72-hour and 2-week follow-up assessments and pain in the past week from baseline to the 12-week followup assessment.
  • Most AEs in both groups were related to the surgery and were of mild (61%) or moderate (27%) severity. There were no serious AEs in the iovera° group attributed to the treatment. There were no device-related or cryoneurolysis procedure-related AEs and no patient who received cryoneurolysis withdrew from the study because of an AE.
  • The most frequently reported AEs for the study were deep vein thrombosis and wound issues associated with the surgical incision.
  • Findings from the PP analysis suggest that preoperative cryoneurolysis in patients with knee osteoarthritis can reduce opioid consumption and improve functional outcomes after TKA.


*P value not reported.
WOMAC = Western Ontario & McMaster Universities Osteoarthritis Index
KOOS = Knee Injury and Osteoarthritis Outcome Score;
PROMIS = Patient-Reported Outcomes Measurement Information System.

References
1. Radnovich R, et al. Osteoarthritis Cartilage. 2017;25(8):1247-1256;
2. Dasa V, et al. Knee. 2016;23(3):523-528;
3. W.M. Mihalko et al. 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 the journal of arthroplasty 36 (2021) 1590–1598