Knee Pain ChronicNCT05286996
Cryoneurolysis for TKA - a Pilot Study
A study testing Iovera - Cryoneurolysis and Local anesthetic in people with Knee Pain Chronic and Osteoarthritis, run by Unity Health Toronto at 1 site in Canada.
Trial summary
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/… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Knee Pain Chronic, Osteoarthritis
- What is being tested?
- Iovera - Cryoneurolysis and Local anesthetic
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- 1 Dec 2022to 1 Dec 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Pregnancy and breastfeeding
- Cryoglobulinemia
- Paroxysmal cold hemoglobinuria
- Cold urticaria
- Raynaud's disease
- Current Opioid use
Show all 9Show fewer
- History of opiate, narcotic and alcohol abuse
- Revision total knee replacement surgery
- Open and/or infected wounds at or near the affected knee
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
St Michael's Hospital
Toronto, Ontario, M5B1W8
Amit Atrey, MD
Amit Atrey, MD
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Knee Pain Chronic, Osteoarthritis
- Being tested
- Iovera - Cryoneurolysis, Local anesthetic
- Keywords
- total knee artroplasty, knee replacement
- Medical subject headings
- Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Iovera - CryoneurolysisDevice
Iovera system delivers precise, controlled doses of cold temperature only to the targeted nerve through a handheld device.
Local anestheticDrug
Also called Placebo
Placebo - local anaesthesia
| Study group | Role | What they receive |
|---|---|---|
| Iovera | Experimental | 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. Receives: Device: Iovera - Cryoneurolysis |
| Placebo | Placebo comparator | Placebo: Usual intervention plus pre-operation placebo. The placebo group will receive short-acting local anaesthesia injection unilaterally to the affected knee. Receives: Drug: Local anesthetic |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months postoperative
Secondary outcomes (5)
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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 12 weeks postoperative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2022
- Study start1 Dec 2022
- Primary completion1 Oct 2023 (estimated)
- Study completion1 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Knee Pain ChronicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel-randomized participant-blinded control trial
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Unity Health Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05286996
- Sponsor's protocol ID
- 22-iovera
- Status last verified
- May 2023
- First submitted
- 1 Mar 2022
- Last updated
- 12 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 26733654Choi 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.
PubMed 26955608Hamilton 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.
PubMed 23575998Wylde 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.
PubMed 21239114Zhou 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.
PubMed 7477749Zhou 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.
PubMed 12623025Radnovich 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.
PubMed 28336454
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cryoneurolysis for Pain Management After Total Knee Arthroplasty - a Pilot Study
- ClinicalTrials.gov ID
- NCT05286996
- Acronym / sponsor ID
- 22-iovera
- Conditions
- Knee Pain Chronic, Osteoarthritis
- Keywords
- total knee artroplasty, knee replacement
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Unity Health TorontoUniversity, hospital or other
- Study start
- 1 Dec 2022 (actual)
- Primary completion
- 1 Oct 2023 (estimated)
- Study completion
- 1 Dec 2023 (estimated)
- First posted
- 18 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Parallel-randomized participant-blinded control trial
| Arm | Type | Receives |
|---|---|---|
| Iovera | Experimental | Device: Iovera - CryoneurolysisCryoneurolysis + 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. |
| Placebo | Placebo comparator | Drug: Local anestheticPlacebo: Usual intervention plus pre-operation placebo. The placebo group will receive short-acting local anaesthesia injection unilaterally to the affected knee. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- Pregnancy and breastfeeding
- Cryoglobulinemia
- Paroxysmal cold hemoglobinuria
- Cold urticaria
- Raynaud's disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Iovera - CryoneurolysisIovera system delivers precise, controlled doses of cold temperature only to the targeted nerve through a handheld device. | Device | Iovera |
| Local anestheticAlso: PlaceboPlacebo - local anaesthesia | Drug | Placebo |
Primary outcome
Patient recruitment rate
Time frame: 12 months postoperative
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.
5 secondary outcomes
Opioid consumption
Time frame: 2 weeks postoperative
Numeric Rating Scale of Pain
Time frame: 2, 6 and 12 weeks postoperative
Oxford Knee score
Time frame: 6 and 12 weeks postoperative
EQ-5D-5L
Time frame: 6 and 12 weeks postoperative
Quality of Recovery
Time frame: 12 weeks postoperative
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2023.
- Background: PubMed 26733654Khan 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.
- Background: PubMed 26955608Choi 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.
- Background: PubMed 23575998Hamilton 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.
- Background: PubMed 21239114Wylde 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.
- Background: PubMed 7477749Zhou 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.
- Background: PubMed 12623025Zhou 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.
- Background: PubMed 28336454Radnovich 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Iovera - Cryoneurolysis and Local anesthetic in people with Knee Pain Chronic and Osteoarthritis, run by Unity Health Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Luana Melo (4168646060 ext. 77286, luana.melo@unityhealth.to), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patient recruitment rate (time frame: 12 months postoperative). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05286996, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2023.