Total Knee ArthroplastyNCT03327220

Treatment With Iovera° for Total Knee Arthroplasty (TKA) Post-Operative Pain

A study testing iovera° in people with Total Knee Arthroplasty, run by Pacira Pharmaceuticals, Inc at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 22 to 79 yearsHealthy volunteers can take part
Conditions the study is for: Total Knee Arthroplasty
What is being tested?: iovera°
Type of treatment: Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 124 participants
Where: 1 siteUnited States
Study dates: 6 Nov 2017to 27 Mar 2019
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 22 to 79 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

22 to 79 years of age
Scheduled to undergo primary unilateral TKA under spinal anesthesia for primary diagnosis of osteoarthritis
Participant is a class I-III on the American Society of Anesthesiology (ASA) Physical Classification System
Anticipation of discharge to home after inpatient acute post-op phase based on age, co-morbidities, home environment, and social support are in favor of discharge to home in the opinion of the Investigator.
Participant is willing and able to give written informed consent.
Participant is fluent in verbal and written English.
Participant is willing and able to comply with study instructions and commit to all follow-up visits for the duration of the study.
Participant is in good general health and free of any systemic disease state or physical condition that might impair evaluation or which in the Investigator's opinion, exposes the participant to an unacceptable risk by study participation.

Who cannot join

Chronic opioid use (defined as daily or almost daily use of opioids for >3 months).
Concurrent painful physical condition, surgery, or musculoskeletal disease that requires analgesic treatment during study follow-up that is not strictly related to the target knee being treated with iovera°, which have the potential to confound the postoperative assessments (e.g., significant pain from other joints, chronic neuropathic pain, concurrent or planned contralateral TKA, concurrent foot, neck, spine, hip, or other musculoskeletal disease, arthritis, or planned surgery, etc.).
Greater than 15° malalignment (varus or valgus) on pre-operative radiograph.
Previous Myoscience treatment.
Previous Partial or Total Knee Arthroplasty. Partial or Total Knee Arthroplasty of the contralateral knee is permitted if surgery was completed at least nine (9) months prior to Screening.
Body Mass Index ≥ 40

Show all 22Show fewer

Prior surgery in the treatment areas that may alter the anatomy of the infrapatellar branch of the saphenous nerve (ISN) or the anterior femoral cutaneous nerve (AFCN) or result in scar tissue in the treatment area.
Any clotting disorder and/or use of an anticoagulant (e.g. warfarin, clopidogrel, etc.) within seven (7) days prior to administration of the device. Low dose aspirin (81mg or less daily) for cardiac prophylaxis allowed.
Any local skin condition at the treatment sites that in the Investigator's opinion would adversely affect treatment or outcomes.
Open and/or infected wound in the treatment areas.
Allergy to lidocaine.
History of cryoglobulinemia
History of paroxysmal cold hemoglobinuria.
History of cold urticaria.
History of Raynaud's disease.
History of opioid or alcohol abuse.
Participant is pregnant or planning to become pregnant while enrolled in the study.
Current enrollment in any investigational drug or device study or participation within 30 days prior to screening.
Currently being treated for related knee injury under worker's compensation claim or equivalent (i.e. legal case).
Any chronic medical condition that in the Investigator's opinion would prevent adequate participation.
Any chronic medication use (prescription, over-the-counter, etc.) that in the Investigator's opinion would affect study participation or participant safety.
For any reason, in the opinion of the Investigator, the participant may not be a suitable candidate for study participation (i.e., history of noncompliance, drug dependency, etc.).

Trial locations and contacts

1 site in 1 country.

United States1 site

Campbell Clinic
Germantown, Tennessee, 38138

Other trials in United States

About this study

Official title: A Post-Market, Prospective, Randomized, Controlled Study To Evaluate The Iovera° Device In Treating Pain Associated With Total Knee Arthroplasty

This study is designed to investigate whether iovera° treatment prior to TKA decreases cumulative participant opioid use over the course of 6 weeks following TKA while maintaining similar levels of pain relief. The study will also investigate whether there is a relationship between participants treated with iovera° and participant reported pain and function as measured by knee injury and osteoarthritis outcomes score (KOOS JR), numeric rating scale (NRS) for pain; use of hospital services post-TKA and improved physical rehabilitation as measured by range of motion.

Conditions: Total Knee Arthroplasty
Being tested: iovera°

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

iovera°Device
The iovera° device applies cold to a target nerve to cause a temporary peripheral nerve block based on a process called Wallerian degeneration (2nd degree axonotmesis) without disrupting connective nerve tissue.

Study groups in NCT03327220
Study group	Role	What they receive
iovera° Device Treatment Group	Experimental	Iovera° device presurgical cryoneurolysis treatment, 5 (+/- 2) days prior to TKA. Additionally, all participants received treatment as per all the standard pre-, peri-, and post-operative surgical protocols. Receives: Device: iovera°
Standard of Care Treatment Group	No intervention	All participants received treatment as per all the standard pre-, peri-, and post-operative surgical protocols.

What is being measured

The primary outcome is the main question the study is designed to answer.

Cumulative Opioid Consumption
The cumulative consumption of opioids was determined from the time of Total Knee Arthroplasty (TKA) surgery to 6 weeks post-TKA surgery. Opioid consumption was converted to morphine milligram equivalents (MME) and participant consumption was verified by pill count at follow-up visits. The cumulative morphine equivalent was divided by the number of days to provide the total daily morphine equivalent (TME) for the participant,
Measured: From the time of TKA surgery to 6 weeks post-TKA surgery

Secondary outcomes (3)

Area Under the Curve (AUC)/Time for Change From Baseline in Knee Injury and Osteoarthritis Outcomes Score (KOOS JR.) Overall Score Through 6 Weeks Post-TKA
The KOOS JR. was a participant completed questionnaire that consists of 7 questions from 3 subscales: stiffness (1 question), pain (4 questions), and function in daily living (2 questions). Standardized answer options are given (5 Likert boxes) and each question was assigned a score from none (0) to extreme (4). A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) was calculated. A positive change from baseline indicates improvement. AUC/time based on Changes from Baseline in KOOS JR. scores through 6 weeks post-TKA, is the AUC of Change in KOOS JR. scores from the Baseline visit through the 6-week visit divided by the number of days from TKA until the 6-week visit. AUC was calculated using the trapezoidal rule and the changes in the KOOS JR. score at the following time points: Baseline (change=0), 72 hours, 2 weeks, and 6 weeks post-TKA.
Measured: Baseline to 6 weeks post-TKA surgery
AUC/Time for Change From Baseline in Numeric Rating Scale (NRS) for Pain Through 6 Weeks Post-TKA
NRS was an 11-point scale for self-reporting of pain intensity by participants. Scores range from 0 to 10, where 0 points equals "no pain" and 10 points equals the "worst pain imaginable". A positive change represented improvement (or reduction) in pain intensity. AUC/time based on Changes from Baseline in NRS Pain score through 6 weeks post-TKA, is the AUC of Change in NRS for Pain score from the Baseline visit through the 6-week visit divided by the number of days from TKA until the 6-week visit. AUC was calculated using the trapezoidal rule and the changes in the NRS for Pain score at the following time points: Baseline (change=0), 72 hours, 2 weeks, and 6 weeks post-TKA.
Measured: Baseline to 6 weeks post-TKA surgery
AUC/Time for Change From Baseline in Timed Get Up and Go (TUG) Tests Through 6 Weeks Post-TKA
The time required by the participants to raise from sitting, walk 10 feet, turn around, walk back and sit back down was measured in seconds. A positive change from baseline indicates improvement. AUC/time based on Changes from Baseline in the TUG test through 6 weeks post-TKA, is the AUC of Change in TUG test from the Baseline visit through the 6-week visit divided by the number of days from TKA until the 6-week visit. AUC was calculated using the trapezoidal rule and the changes in the TUG test at the following time points: Baseline (change=0), 72 hours, 2 weeks, and 6 weeks post-TKA.
Measured: Baseline to 6 weeks post-TKA surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Nov 201727 Mar 2019

First posted31 Oct 2017
Study start6 Nov 2017
Primary completion27 Mar 2019
Study completion27 Mar 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Total Knee ArthroplastyStudies 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: The active group will receive the iovera° treatment prior to a TKA. The control group will receive a TKA and no iovera° treatment.
Masking: None (open label)
Enrolment: 124 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03327220
Sponsor's protocol ID: MYO-1265
Status last verified: May 2021
First submitted: 26 Oct 2017
Last updated: 21 May 2021
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: No
FDA-regulated device: Yes

Publications

Mihalko WM, Kerkhof AL, Ford MC, Crockarell JR Jr, Harkess JW, Guyton JL. 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. J Arthroplasty. 2021 May;36(5):1590-1598. doi: 10.1016/j.arth.2020.11.013. Epub 2020 Nov 14.
PubMed 33279353

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 3
REGN7508 Versus Apixaban and Enoxaparin for Thromboprophylaxis After Total Knee Arthroplasty in Adults
Venous Thromboembolism (VTE)
Recruiting
SII Levels Following iPACK Block With Adductor Canal Block in Knee Arthroplasty
Knee Osteoarthritis
Enrolling by invitationObservational study
Persona SoluTion PPS Femur PMCF
Rhematoid Arthritis, Osteo Arthritis of the Knee
Recruiting
ACB and iPACK Blocks With Intravenous Dexamethasone and Perineural Dexmedetomidine in Total Knee Arthroplasty
Knee Osteoarthritis
RecruitingPhase 3
REGN7508 Versus Acetylsalicylic Acid (ASA) for Venous Thromboprophylaxis After Total Knee Arthroplasty in Adult Participants
Symptomatic Venous Thromboembolism (VTE)

All Total Knee Arthroplasty trials

Study at a glance

From the registry record, last updated by the sponsor on 21 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Post-Market, Prospective, Randomized, Controlled Study To Evaluate The Iovera° Device In Treating Pain Associated With Total Knee Arthroplasty
ClinicalTrials.gov ID: NCT03327220
Acronym / sponsor ID: MYO-1265
Conditions: Total Knee Arthroplasty
Study type: Interventional
Recruitment status: Completed
Enrolment: 124 participants (actual)
Lead sponsor: Pacira Pharmaceuticals, IncIndustry (pharma, biotech, devices)
Study start: 6 Nov 2017 (actual)
Primary completion: 27 Mar 2019 (actual)
Study completion: 27 Mar 2019 (actual)
First posted: 31 Oct 2017 (actual)
Results: Posted 21 May 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: The active group will receive the iovera° treatment prior to a TKA. The control group will receive a TKA and no iovera° treatment.

Arm	Type	Receives
iovera° Device Treatment Group	Experimental	Device: iovera°Iovera° device presurgical cryoneurolysis treatment, 5 (+/- 2) days prior to TKA. Additionally, all participants received treatment as per all the standard pre-, peri-, and post-operative surgical protocols.
Standard of Care Treatment Group	No intervention	–All participants received treatment as per all the standard pre-, peri-, and post-operative surgical protocols.

Who may qualify

Ages: 22 to 79 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

22 to 79 years of age
Scheduled to undergo primary unilateral TKA under spinal anesthesia for primary diagnosis of osteoarthritis
Participant is a class I-III on the American Society of Anesthesiology (ASA) Physical Classification System
Anticipation of discharge to home after inpatient acute post-op phase based on age, co-morbidities, home environment, and social support are in favor of discharge to home in the opinion of the Investigator.
Participant is willing and able to give written informed consent.

Key exclusion criteria (22 listed)

Chronic opioid use (defined as daily or almost daily use of opioids for >3 months).
Concurrent painful physical condition, surgery, or musculoskeletal disease that requires analgesic treatment during study follow-up that is not strictly related to the target knee being treated with iovera°, which have the potential to confound the postoperative assessments (e.g., significant pain from other joints, chronic neuropathic pain, concurrent or planned contralateral TKA, concurrent foot, neck, spine, hip, or other musculoskeletal disease, arthritis, or planned surgery, etc.).
Greater than 15° malalignment (varus or valgus) on pre-operative radiograph.
Previous Myoscience treatment.
Previous Partial or Total Knee Arthroplasty. Partial or Total Knee Arthroplasty of the contralateral knee is permitted if surgery was completed at least nine (9) months prior to Screening.

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°The iovera° device applies cold to a target nerve to cause a temporary peripheral nerve block based on a process called Wallerian degeneration (2nd degree axonotmesis) without disrupting connective nerve tissue.	Device	iovera° Device Treatment Group

Primary outcome

Cumulative Opioid Consumption
Time frame: From the time of TKA surgery to 6 weeks post-TKA surgery
The cumulative consumption of opioids was determined from the time of Total Knee Arthroplasty (TKA) surgery to 6 weeks post-TKA surgery. Opioid consumption was converted to morphine milligram equivalents (MME) and participant consumption was verified by pill count at follow-up visits. The cumulative morphine equivalent was divided by the number of days to provide the total daily morphine equivalent (TME) for the participant,

3 secondary outcomes

Area Under the Curve (AUC)/Time for Change From Baseline in Knee Injury and Osteoarthritis Outcomes Score (KOOS JR.) Overall Score Through 6 Weeks Post-TKA
Time frame: Baseline to 6 weeks post-TKA surgery
AUC/Time for Change From Baseline in Numeric Rating Scale (NRS) for Pain Through 6 Weeks Post-TKA
Time frame: Baseline to 6 weeks post-TKA surgery
AUC/Time for Change From Baseline in Timed Get Up and Go (TUG) Tests Through 6 Weeks Post-TKA
Time frame: Baseline to 6 weeks post-TKA surgery

Results and safety

Results posted to the registry on 21 May 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Iovera° Device Treatment Group	62	57
Standard of Care Treatment Group	62	58

Primary outcome: Cumulative Opioid Consumption

Time frame: From the time of TKA surgery to 6 weeks post-TKA surgery. Mean (Standard Error). Unit: TME

Measure	Iovera° Device Treatment Group n = 59	Standard of Care Treatment Group n = 60
Value	4.8 (0.7)	6.1 (0.7)

Iovera° Device Treatment Group vs Standard of Care Treatment Group: Difference in Means: 1.3 (95% CI -0.6 to 3.2), p = 0.0841, t-test, 1 sided

Population analysed: Intent-to-treat (ITT) population included all participants who were randomized into the study. Overall number analyzed is the number of participants with data available for analysis.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first treatment up to the end of the study (Up to approximately 12 weeks). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Iovera° Device Treatment Group	2 of 59 (3.4%)	4 of 59 (6.8%)	0 of 62
Standard of Care Treatment Group	2 of 60 (3.3%)	3 of 60 (5%)	0 of 62

Limitations and caveats (from the sponsor): This study was acquired from another sponsor. Results for the Primary Outcome Measure, Cumulative Opioid Consumption, are reported for the Time Frame (From the time of TKA surgery to 6 weeks post-TKA surgery) because the results for the Time Frame (From the time of hospital discharge to 6 weeks post-TKA surgery) are not available.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33279353Mihalko WM, Kerkhof AL, Ford MC, Crockarell JR Jr, Harkess JW, Guyton JL. 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. J Arthroplasty. 2021 May;36(5):1590-1598. doi: 10.1016/j.arth.2020.11.013. Epub 2020 Nov 14.

Related trials for Total Knee Arthroplasty

RecruitingPhase 3
REGN7508 Versus Apixaban and Enoxaparin for Thromboprophylaxis After Total Knee Arthroplasty in Adults
Venous Thromboembolism (VTE)
Recruiting
SII Levels Following iPACK Block With Adductor Canal Block in Knee Arthroplasty
Knee Osteoarthritis
Enrolling by invitationObservational study
Persona SoluTion PPS Femur PMCF
Rhematoid Arthritis, Osteo Arthritis of the Knee
Recruiting
ACB and iPACK Blocks With Intravenous Dexamethasone and Perineural Dexmedetomidine in Total Knee Arthroplasty
Knee Osteoarthritis
RecruitingPhase 3
REGN7508 Versus Acetylsalicylic Acid (ASA) for Venous Thromboprophylaxis After Total Knee Arthroplasty in Adult Participants
Symptomatic Venous Thromboembolism (VTE)

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.

William Mihalko, MD, PhD principal investigator

UTHSC - COM - Orthopaedic Surgery & Biomedical Engineering

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° in people with Total Knee Arthroplasty, run by Pacira Pharmaceuticals, Inc at 1 site in United States.

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 8 inclusion and 22 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: finished, as of the sponsor's last update on 21 May 2021. 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 United States. 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. 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?

Yes. Results are posted in the registry (first posted 21 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cumulative Opioid Consumption (time frame: From the time of TKA surgery to 6 weeks post-TKA surgery). 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 NCT03327220, which also lists 1 linked publication.

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 21 May 2021.