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.
Trial summary
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. Read more about this study
- 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.
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 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.
- 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)
Sponsor and investigators
- Lead sponsor
- Pacira Pharmaceuticals, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- William Mihalko, MD, PhD, Principal investigator, UTHSC - COM - Orthopaedic Surgery & Biomedical Engineering
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
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.
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.
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
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.
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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.
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.