Cryoneurolysis for TKA - a Pilot Study

Cryoneurolysis for Pain Management After Total Knee Arthroplasty - a Pilot Study

Total Knee Arthroplasty (TKA) is also known as a knee replacement. It is one of the most common orthopaedic (bone) surgeries performed and is usually very successful, but some people who have had a knee replacement feel pain that lasts for at least 3 months after surgery and thus continue to take pain control/ analgesic (opioids) medication. Opiates are medications like morphine.

Pain post-surgery can make it difficult to recover and return to daily activities. A better control of pain before the surgery, can help people feel less pain, recover faster, and use less opioids after surgery.

Cryoneurolysis means freezing the nerves that can cause pain. It uses very low temperatures in a specific body part (e.g., nerves to the knee) to freeze the pain nerves and therefore reduce the pain. When applied before the surgery it might help with postoperative pain after knee replacement.

This study will evaluate Iovera, a cryoneurolysis handheld device commercially available in Canada that delivers freezing cold to a target nerve by using nitrous oxide. Cryoneurolysis can relieve pain and symptoms associated with osteoarthritis of the knee for up to 90 days.

Study Overview

• Status: Recruiting
• Conditions: Osteoarthritis; Knee Pain Chronic
• Intervention / Treatment: Device: Iovera - Cryoneurolysis; Drug: Local anesthetic

Detailed Description

Patients undergoing total knee replacement (TKA) often experience a significant amount of pain during the immediate postoperative period, thus appropriate pain management before, during and after the surgery is a key component of patient satisfaction and better outcomes.

Opioids are the most commonly prescribed drugs to manage postoperative orthopaedic pain; however, their well-known side effects, such as nausea, vomiting and the potential high risk for dependence, can slow down recovery and lead to substance disorders.

Studies have reported, that more than 20% of patients receiving TKA experience persistent and unchanged pain post-surgery. Moreover, 15 to 25% of TKA patients continue the use of opioids at 3 months after surgery, 35% of patients report pain that interferes with their activities of daily living 4 months after surgery.

Adequate pain management before the surgery may prevent or reduce the rate of persistent pain and opioid usage after TKA. Cryoneurolysis is a minimally invasive procedure that uses a small probe to freeze [at very low temperatures - below -20oC] the target nerve. It can promote regeneration of the structure and function of the affected nerve. It has shown promising short and long-term results in a variety of acute and chronic pain conditions.

Retrospective studies revealed that preoperative cryoneurolysis might be efficacious in attenuating pain improving function and reducing opioid prescription 12 weeks after TKA. However, the studies are mostly retrospective, with small numbers of patients and not standardized knee specific outcomes.

This is a pilot randomized clinical trial to establish the feasibility of administering the study device (Iovera) to our target population as well as to test and refine the recruitment criteria, study design, patient acceptability, and operational strategies for use in a large definitive study.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Amit Atrey; Phone Number: 416- 864-5342; Email: amit.atrey@unityhealth.to
• Study Contact Backup: Name: Luana Melo; Phone Number: 77286 4168646060; Email: luana.melo@unityhealth.to

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5B1W8
      • Recruiting
      • St Michael's Hospital
      • Principal Investigator: Amit Atrey, MD
      • Contact: Amit Atrey, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female patients
• 18 to 80 years of age
• Patients with radiographic confirmation and clinical correlation for severe osteoarthritis diagnosis with an indication for total knee replacement
• Patients undergoing primary unilateral total knee replacement
• No previous unilateral knee injection (steroids/biologics) within 6 months of study
• The patient is able to read and understand English and provide informed consent to participation in the study

Exclusion Criteria:

• Pregnancy and breastfeeding
• Cryoglobulinemia
• Paroxysmal cold hemoglobinuria
• Cold urticaria
• Raynaud's disease
• Current Opioid use
• History of opiate, narcotic and alcohol abuse
• Revision total knee replacement surgery
• Open and/or infected wounds at or near the affected knee

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Iovera; Cryoneurolysis + standard of care: Usual intervention plus pre-operation Iovera treatment. Patients will receive local anaesthesia unilaterally to the affected knee prior to the treatment and then the anesthesiologist will administer the freezing cold therapy (Iovera device) to the affected knee.	Device: Iovera - Cryoneurolysis; Iovera system delivers precise, controlled doses of cold temperature only to the targeted nerve through a handheld device.
Placebo Comparator: Placebo; Placebo: Usual intervention plus pre-operation placebo. The placebo group will receive short-acting local anaesthesia injection unilaterally to the affected knee.	Drug: Local anesthetic; Placebo - local anaesthesia; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient recruitment rate	The primary objective of the pilot trial is to establish the feasibility of a larger definitive trial by successfully recruiting 20 patients over a 12-month period.	12 months postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid consumption	Cumulative opioid consumption will be assessed by drug diaries that patients will bring back to the hospital visit at 2 week follow up appointment.	2 weeks postoperative
Numeric Rating Scale of Pain	It consists of 11-point numeric scale ranges from '0' representing one pain extreme (e.g. "no pain") to '10' representing the other pain extreme.	2, 6 and 12 weeks postoperative
Oxford Knee score	is a validated 12-item patient-reported outcome specifically designed and developed to assess function and pain after total knee replacement surgery. It scores from 0 (might indicate severe arthritis) to 48 (normal joint function).	6 and 12 weeks postoperative
EQ-5D-5L	It is a health-related quality of life measure that consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ-VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The EQ-VAS records the patient's self-rated health on a vertical visual analogue scale.	6 and 12 weeks postoperative
Quality of Recovery	The 15-item Quality of Recovery (QoR-15) scale is a validated, simple, reliable, multidimensional questionnaire that measures the quality of recovery after surgery. Fifteen questions assess five domains of patient-reported health status: pain, physical comfort, physical independence, psychological support and emotional state.	12 weeks postoperative

Collaborators and Investigators

• Sponsor: Unity Health Toronto

Publications and helpful links

General Publications

• Radnovich R, Scott D, Patel AT, Olson R, Dasa V, Segal N, Lane NE, Shrock K, Naranjo J, Darr K, Surowitz R, Choo J, Valadie A, Harrell R, Wei N, Metyas S. Cryoneurolysis to treat the pain and symptoms of knee osteoarthritis: a multicenter, randomized, double-blind, sham-controlled trial. Osteoarthritis Cartilage. 2017 Aug;25(8):1247-1256. doi: 10.1016/j.joca.2017.03.006. Epub 2017 Mar 20.
• Wylde V, Hewlett S, Learmonth ID, Dieppe P. Persistent pain after joint replacement: prevalence, sensory qualities, and postoperative determinants. Pain. 2011 Mar;152(3):566-572. doi: 10.1016/j.pain.2010.11.023. Epub 2011 Jan 15.
• Hamilton DF, Lane JV, Gaston P, Patton JT, Macdonald D, Simpson AH, Howie CR. What determines patient satisfaction with surgery? A prospective cohort study of 4709 patients following total joint replacement. BMJ Open. 2013 Apr 9;3(4):e002525. doi: 10.1136/bmjopen-2012-002525. Print 2013.
• Choi YJ, Ra HJ. Patient Satisfaction after Total Knee Arthroplasty. Knee Surg Relat Res. 2016 Mar;28(1):1-15. doi: 10.5792/ksrr.2016.28.1.1. Epub 2016 Feb 29.
• Khan M, Osman K, Green G, Haddad FS. The epidemiology of failure in total knee arthroplasty: avoiding your next revision. Bone Joint J. 2016 Jan;98-B(1 Suppl A):105-12. doi: 10.1302/0301-620X.98B1.36293.
• Zhou L, Kambin P, Casey KF, Bonner FJ, O'Brien E, Shao Z, Ou S. Mechanism research of cryoanalgesia. Neurol Res. 1995 Aug;17(4):307-11. doi: 10.1080/01616412.1995.11740333.
• Zhou L, Shao Z, Ou S. Cryoanalgesia: electrophysiology at different temperatures. Cryobiology. 2003 Feb;46(1):26-32. doi: 10.1016/s0011-2240(02)00160-8.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: March 1, 2022
• First Submitted That Met QC Criteria: March 9, 2022
• First Posted (Actual): March 18, 2022

Study Record Updates

• Last Update Posted (Actual): May 12, 2023
• Last Update Submitted That Met QC Criteria: May 10, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: knee replacement; total knee artroplasty
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local
• Other Study ID Numbers: 22-iovera

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No