Trial Outcomes & Findings for Treatment With Iovera° for Total Knee Arthroplasty (TKA) Post-Operative Pain (NCT NCT03327220)
NCT ID: NCT03327220
Last Updated: 2021-05-21
Results Overview
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,
COMPLETED
NA
124 participants
From the time of TKA surgery to 6 weeks post-TKA surgery
2021-05-21
Participant Flow
Participant milestones
| Measure |
Iovera° Device Treatment Group
Iovera° device presurgical cryoneurolysis treatment, 5 (+/- 2) days prior to total knee arthroplasty (TKA). Additionally, all participants received treatment as per all the standard pre-, peri-, and post-operative surgical protocols.
|
Standard of Care Treatment Group
All participants received treatment as per all the standard pre-, peri-, and post-operative surgical protocols.
|
|---|---|---|
|
Overall Study
STARTED
|
62
|
62
|
|
Overall Study
Safety Population: Received Study Treatment
|
59
|
60
|
|
Overall Study
COMPLETED
|
57
|
58
|
|
Overall Study
NOT COMPLETED
|
5
|
4
|
Reasons for withdrawal
| Measure |
Iovera° Device Treatment Group
Iovera° device presurgical cryoneurolysis treatment, 5 (+/- 2) days prior to total knee arthroplasty (TKA). Additionally, all participants received treatment as per all the standard pre-, peri-, and post-operative surgical protocols.
|
Standard of Care Treatment Group
All participants received treatment as per all the standard pre-, peri-, and post-operative surgical protocols.
|
|---|---|---|
|
Overall Study
Adverse Event (AE)/Serious Adverse Event (SAE)
|
1
|
2
|
|
Overall Study
Investigator Decision
|
2
|
0
|
|
Overall Study
Missed Visit 6 (Week 6 Visit)
|
0
|
1
|
|
Overall Study
Fungal infection
|
1
|
0
|
|
Overall Study
Discharged to Rehabilitation
|
0
|
1
|
|
Overall Study
Missing
|
1
|
0
|
Baseline Characteristics
Treatment With Iovera° for Total Knee Arthroplasty (TKA) Post-Operative Pain
Baseline characteristics by cohort
| Measure |
Iovera° Device Treatment Group
n=62 Participants
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
n=62 Participants
All participants received treatment as per all the standard pre-, peri-, and post-operative surgical protocols.
|
Total
n=124 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65.5 years
STANDARD_DEVIATION 8.2 • n=5 Participants
|
66.2 years
STANDARD_DEVIATION 7.1 • n=7 Participants
|
65.9 years
STANDARD_DEVIATION 7.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
31 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
67 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
57 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
62 Participants
n=5 Participants
|
62 Participants
n=7 Participants
|
124 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
10 participants
n=5 Participants
|
15 participants
n=7 Participants
|
25 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
52 participants
n=5 Participants
|
47 participants
n=7 Participants
|
99 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From the time of TKA surgery to 6 weeks post-TKA surgeryPopulation: 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.
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,
Outcome measures
| Measure |
Iovera° Device Treatment Group
n=59 Participants
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
n=60 Participants
All participants received treatment as per all the standard pre-, peri-, and post-operative surgical protocols.
|
|---|---|---|
|
Cumulative Opioid Consumption
|
4.8 TME
Standard Error 0.7
|
6.1 TME
Standard Error 0.7
|
SECONDARY outcome
Timeframe: Baseline to 6 weeks post-TKA surgeryPopulation: ITT population included all participants who were randomized into the study.
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.
Outcome measures
| Measure |
Iovera° Device Treatment Group
n=62 Participants
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
n=62 Participants
All participants received treatment as per all the standard pre-, peri-, and post-operative surgical protocols.
|
|---|---|---|
|
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
|
10.3 score on a scale/days
Standard Error 1.6
|
8.4 score on a scale/days
Standard Error 1.4
|
SECONDARY outcome
Timeframe: Baseline to 6 weeks post-TKA surgeryPopulation: ITT population included all participants who were randomized into the study. Overall number analyzed is the number of participants with data available for analysis at the given timepoint.
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.
Outcome measures
| Measure |
Iovera° Device Treatment Group
n=58 Participants
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
n=59 Participants
All participants received treatment as per all the standard pre-, peri-, and post-operative surgical protocols.
|
|---|---|---|
|
AUC/Time for Change From Baseline in Numeric Rating Scale (NRS) for Pain Through 6 Weeks Post-TKA
Pain in The Past 7 Days
|
2.2 score on a scale/days
Standard Deviation 2.1
|
1.7 score on a scale/days
Standard Deviation 1.9
|
|
AUC/Time for Change From Baseline in Numeric Rating Scale (NRS) for Pain Through 6 Weeks Post-TKA
Pain Right Now
|
1.9 score on a scale/days
Standard Deviation 2.7
|
1.5 score on a scale/days
Standard Deviation 2.3
|
SECONDARY outcome
Timeframe: Baseline to 6 weeks post-TKA surgeryPopulation: ITT population included all participants who were randomized into the study. Overall number analyzed is the number of participants with data available for analysis.
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.
Outcome measures
| Measure |
Iovera° Device Treatment Group
n=57 Participants
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
n=59 Participants
All participants received treatment as per all the standard pre-, peri-, and post-operative surgical protocols.
|
|---|---|---|
|
AUC/Time for Change From Baseline in Timed Get Up and Go (TUG) Tests Through 6 Weeks Post-TKA
|
-1.2 seconds/days
Standard Deviation 5.5
|
-0.4 seconds/days
Standard Deviation 11.3
|
Adverse Events
Iovera° Device Treatment Group
Standard of Care Treatment Group
Serious adverse events
| Measure |
Iovera° Device Treatment Group
n=59 participants at risk
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
n=60 participants at risk
All participants received treatment as per all the standard pre-, peri-, and post-operative surgical protocols.
|
|---|---|---|
|
Vascular disorders
Bilateral Pulmonary Emboli
|
1.7%
1/59 • From first treatment up to the end of the study (Up to approximately 12 weeks)
All-cause Mortality: ITT population included all randomized participants. Serious Adverse Events and Adverse Events: Safety population included all participants who received study treatment.
|
0.00%
0/60 • From first treatment up to the end of the study (Up to approximately 12 weeks)
All-cause Mortality: ITT population included all randomized participants. Serious Adverse Events and Adverse Events: Safety population included all participants who received study treatment.
|
|
Vascular disorders
R/O Popliteal Arterial Aneurysm
|
1.7%
1/59 • From first treatment up to the end of the study (Up to approximately 12 weeks)
All-cause Mortality: ITT population included all randomized participants. Serious Adverse Events and Adverse Events: Safety population included all participants who received study treatment.
|
0.00%
0/60 • From first treatment up to the end of the study (Up to approximately 12 weeks)
All-cause Mortality: ITT population included all randomized participants. Serious Adverse Events and Adverse Events: Safety population included all participants who received study treatment.
|
|
Psychiatric disorders
Neuropsychotic/seizures
|
1.7%
1/59 • From first treatment up to the end of the study (Up to approximately 12 weeks)
All-cause Mortality: ITT population included all randomized participants. Serious Adverse Events and Adverse Events: Safety population included all participants who received study treatment.
|
1.7%
1/60 • From first treatment up to the end of the study (Up to approximately 12 weeks)
All-cause Mortality: ITT population included all randomized participants. Serious Adverse Events and Adverse Events: Safety population included all participants who received study treatment.
|
|
Skin and subcutaneous tissue disorders
Anaphylaxis
|
1.7%
1/59 • From first treatment up to the end of the study (Up to approximately 12 weeks)
All-cause Mortality: ITT population included all randomized participants. Serious Adverse Events and Adverse Events: Safety population included all participants who received study treatment.
|
1.7%
1/60 • From first treatment up to the end of the study (Up to approximately 12 weeks)
All-cause Mortality: ITT population included all randomized participants. Serious Adverse Events and Adverse Events: Safety population included all participants who received study treatment.
|
Other adverse events
| Measure |
Iovera° Device Treatment Group
n=59 participants at risk
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
n=60 participants at risk
All participants received treatment as per all the standard pre-, peri-, and post-operative surgical protocols.
|
|---|---|---|
|
Vascular disorders
R/O Deep vein thrombosis
|
6.8%
4/59 • From first treatment up to the end of the study (Up to approximately 12 weeks)
All-cause Mortality: ITT population included all randomized participants. Serious Adverse Events and Adverse Events: Safety population included all participants who received study treatment.
|
5.0%
3/60 • From first treatment up to the end of the study (Up to approximately 12 weeks)
All-cause Mortality: ITT population included all randomized participants. Serious Adverse Events and Adverse Events: Safety population included all participants who received study treatment.
|
Additional Information
Kent Jones/ Sr. Director, Quality and Medical Affairs
Pacira CryoTech, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place