Study to Evaluate the Iovera° Device for Temporary Relief From Knee Pain

• Sponsor: Pacira CryoTech, Inc., a wholly owned subsidiary of Pacira BioSciences, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02260921
• Collaborator: (none)
• Enrollment: 180
• Locations: 17
• Arms: 2
• Actual Duration (Months): 19.4
• Patients Per Site: 10.6
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This purpose of this study is to evaluate the effectiveness and safety of the iovera° device for the temporary reduction of pain associated with knee osteoarthritis.

Condition or Disease	Intervention/Treatment	Phase
Knee Osteoarthritis	Device: iovera°; Device: Sham Comparator	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 180 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Prospective, Double-Blind, Randomized Controlled Study to Evaluate the Effectiveness and Safety of the Iovera° Device for the Temporary Relief of Pain Associated With Knee Osteoarthritis
• Actual Study Start Date: Oct 20, 2014
• Actual Primary Completion Date: Feb 1, 2016
• Actual Study Completion Date: May 31, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: iovera° Treatment Treatment with the iovera° device administered by a trained investigator to treat knee pain.	Device: iovera°
Sham Comparator: Sham Treatment Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.	Device: Sham Comparator

Outcome Measures

Primary Outcome Measures

1. Absolute Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale Score at Day 30 [Baseline to Day 30]

   The WOMAC is a tri-dimensional, disease-specific, patient-reported outcome measure. It consists of 24 questions [each question is presented in a numerical rating scale format with possible values between 0= No (best) to 10= Extreme (worst)] with 5 questions regarding pain [possible subscale score 0 to 50], 2 questions regarding stiffness [possible subscale score 0 to 20] and 17 questions regarding function difficulty [possible subscale score 0 to 170]. A negative change from Baseline indicates improvement. An Analysis of Covariance (ANCOVA) model was used for analyses.

Secondary Outcome Measures

1. Change From Baseline in Visual Analog Scale (VAS) at Day 30 [Baseline to Day 30]

   VAS pain assessment is a measure of pain intensity. The scale is made up of a 10 centimeter (cm) [100 millimeter (mm)] horizontal line. The far left of the horizontal line is labeled "no pain" while the far right of the horizontal line is labeled "worst imaginable pain". A negative change from Baseline indicates improvement. An ANCOVA model was used for analyses.

2. Change From Baseline in Total WOMAC Score at Day 30 [Baseline to Day 30]

   The WOMAC is a tri-dimensional, disease-specific, patient-reported outcome measure. It consists of 24 questions [each question is presented in a numerical rating scale format with possible values between 0= No (best) to 10= Extreme (worst)] with 5 questions regarding pain [possible subscale score 0 to 50], 2 questions regarding stiffness [possible subscale score 0 to 20] and 17 questions regarding function difficulty [possible subscale score 0 to 170]. The WOMAC total score was calculated by summing the 3 subscales for a total possible score of 0 to 240. A negative change from Baseline indicates improvement. An ANCOVA model was used for analyses.

3. Change From Baseline in VAS at Day 60 [Baseline to Day 60]

   VAS pain assessment is a measure of pain intensity. The scale is made up of a 10 cm (100 mm) horizontal line. The far left of the horizontal line is labeled "no pain" while the far right of the horizontal line is labeled "worst imaginable pain". A negative change from Baseline indicates improvement. An ANCOVA model was used for analyses.

4. WOMAC Pain Score Responder Rate at Day 30 [Day 30]

   WOMAC Pain Score Responder Rate is defined as the percentage of participants with at least a 30% reduction in the WOMAC pain score at Day 30 compared to Baseline. WOMAC is a tri-dimensional, disease-specific, patient-reported outcome measure. It consists of 24 questions [each question is presented in a numerical rating scale format with possible values between 0= No to 10= Extreme] with the first 5 questions regarding pain [possible subscale score 0 (best) to 50 (worst)].

5. VAS Responder Rate at Day 30 [Day 30]

   VAS Responder Rate is defined as the percentage of participants with at least a 30% reduction in VAS at Day 30 compared to Baseline VAS pain assessment is a measure of pain intensity. The scale is made up of a 10 cm (100 mm) horizontal line. The far left of the horizontal line is labeled "no pain" while the far right of the horizontal line is labeled "worst imaginable pain".

6. Change From Baseline in Total WOMAC Score at Day 60 [Baseline to Day 60]

   The WOMAC is a tri-dimensional, disease-specific, patient-reported outcome measure. It consists of 24 questions [each question is presented in a numerical rating scale format with possible values between 0= No (best) to 10= Extreme (worst)] with 5 questions regarding pain [possible subscale score 0 to 50], 2 questions regarding stiffness [possible subscale score 0 to 20] and 17 questions regarding function difficulty [possible subscale score 0 to 170]. The WOMAC total score was calculated by summing the 3 subscales for a total possible score of 0 to 240. A negative change from Baseline indicates improvement.

7. VAS Responder Rate at Day 60 [Day 60]

   VAS Responder Rate is defined as the percentage of participants with at least a 30% reduction in VAS at Day 60 compared to Baseline. VAS pain assessment is a measure of pain intensity. The scale is made up of a 10 cm (100 mm) horizontal line. The far left of the horizontal line is labeled "no pain" while the far right of the horizontal line is labeled "worst imaginable pain".

8. WOMAC Pain Score Responder Rate at Day 60 [Day 60]

   WOMAC Pain Score Responder Rate is defined as the percentage of participants with at least a 30% reduction in the WOMAC pain score at Day 60 compared to Baseline. WOMAC is a tri-dimensional, disease-specific, patient-reported outcome measure. It consists of 24 questions [each question is presented in a numerical rating scale format with possible values between 0= No (best) to 10= Extreme (worst)] with the first 5 questions regarding pain [possible subscale score 0 to 50].

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• 35 - 75 years of age

• American College of Rheumatology (ACR) criteria for osteoarthritis of the knee. This includes radiographic evidence of osteophytes and at least one of the following: age ≥ 50 years old, morning stiffness ≤ 30 minute duration or crepitus on motion.

• Grade II or III osteoarthritis of the knee as determined by Kellgren-Lawrence classification grading scale on anteroposterior (AP) x-ray within previous 6 months.

• Participants are ambulatory without assistive devices.

• Knee pain of ≥ 40 mm on Visual Analog Scale (VAS) when performing one of two movements that elicit the worst pain: standing from a seated position or walking up/down stairs.

• Participant reports knee pain in the anterior and/or inferior aspect of the knee as documented on the knee pain map in the appropriate areas.

• A diagnostic lidocaine (without epinephrine) block of the infrapatellar branch of the saphenous nerve results in a 50% reduction in the VAS pain assessment score when performing the activity that elicits the worst pain: standing from a seated position or walking up/down stairs.

• Participant is able to tolerate a washout of prescription and over-the-counter pain relief for a duration of 5 times the half-life of the medication prior to the Baseline visit.

Participant is able to tolerate a washout of adjunctive therapies for knee pain for 72 hours prior to the Baseline visit.

• Western Ontario and McMaster Osteoarthritis Index (WOMAC) NRS3.1 Pain subscore ≥ 20 at Baseline/Visit 2.

• Participant is able to tolerate discontinuation of all pain medication throughout the duration of the study. Acetaminophen may be used as rescue medication with a maximum dose of 4g per day.

• Participant is able to tolerate discontinuation of rescue medication, acetaminophen, for 24 hours prior to all follow-up visits.

• Prescription and over-the-counter pain medications must be maintained on a stable schedule for at least two weeks prior to screening.

• Participant is willing and able to give written informed consent.

• 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.

Exclusion Criteria:

• History of a partial or full knee replacement of the knee to be treated.

• Planned partial or full knee replacement within the next 12 months in knee to be treated.

• Previous myoscience Focused Cold Therapy^TM (FCTTM) treatment.

• Viscosupplementation within the previous 6 months in knee to be treated.

• Participant reports the majority of knee pain outside of the anterior/inferior aspect of the knee.

• Intra-articular steroid injection in the knee to be treated within previous 3 months.

• Gross deformity of the knee including varus or valgus.

• Started physical therapy of the knee to be treated within 3 months of screening.

• Received acupuncture for knee pain within 3 months prior to screening.

• Body Mass Index ≥ 35.

• Prior surgery in the treatment area that may alter the anatomy of the infrapatellar branch of the saphenous nerve or result in scar tissue in the treatment area.

• Open and/or infected wound in the treatment area.

• Disease of the spine, hip, contralateral knee or other lower extremity joint of sufficient degree affecting the assessment of the treated knee.

• Acetaminophen intolerance or allergy.

• Allergy to lidocaine.

• History of cryoglobulinemia

• History of paroxysmal cold hemoglobinuria.

• History of cold urticaria.

• History of Raynaud's disease.

• History of pes anserinus bursitis in the knee to be treated.

• Use of extended-release or long-acting opioids within previous 3 months.

• Use of immediate-release opioids for more than 3 days per week within previous month.

• 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.

• Any additional diagnosis that in the opinion of the Investigator directly contributes to knee pain.

• Any concomitant inflammatory disease or other condition that affects the joints (e.g. rheumatoid arthritis, metabolic bone disease, gout, active infection, etc.)

• Any clotting disorder and/or use of an anticoagulant (e.g., aspirin, warfarin, clopidogrel, etc.) within seven (7) days prior to administration of the device.

• Any local skin condition at the treatment site that in the Investigator's opinion would adversely affect treatment or outcomes.

• 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 Subject safety.

• For any reason, in the opinion of the Investigator, the Subject may not be a suitable candidate for study participation (i.e., history of noncompliance, drug dependency, any related knee injury due to a worker's compensation claim, etc.).

• Known liver dysfunction.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medvin Clinical Research	Covina	California	United States	91723
2	UC Davis Center for Musculoskeletal Health	Sacramento	California	United States	95817
3	Coastal Orthopedics and Sports Medicine of Southwest Florida, PA	Bradenton	Florida	United States	34203
4	Shrock Orthpedic Research	Fort Lauderdale	Florida	United States	33316
5	Health Awareness	Jupiter	Florida	United States	33458
6	JM Clinical Research	South Miami	Florida	United States	33143
7	Injury Care Medical Center	Boise	Idaho	United States	83713
8	Rockford Orthopedic Associates, LTD	Rockford	Illinois	United States	61114
9	Kansas University Medical Center	Fairway	Kansas	United States	66205
10	Kansas City Bone and Joint Clinic	Overland Park	Kansas	United States	66211
11	Covington Orthopedic and Sports Medicine Institute	Covington	Louisiana	United States	70433
12	LHU HSC Department of Orthopaedics	New Orleans	Louisiana	United States	70112
13	Arthritis Treatment Center	Frederick	Maryland	United States	21702
14	Triangle Orthopaedic Associates, P.A.	Durham	North Carolina	United States	27704
15	Blair Orthopedic Associates, Inc.	Altoona	Pennsylvania	United States	16602
16	PCET Research Center	Knoxville	Tennessee	United States	37909
17	Spokane Joint Replacement Center	Spokane	Washington	United States	99218

Sponsors and Collaborators

• Pacira CryoTech, Inc., a wholly owned subsidiary of Pacira BioSciences, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pacira CryoTech, Inc., a wholly owned subsidiary of Pacira BioSciences, Inc.
• ClinicalTrials.gov Identifier: NCT02260921
• Other Study ID Numbers: MYO-0946
• First Posted: Oct 9, 2014
• Last Update Posted: Feb 2, 2021
• Last Verified: Jan 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee

Study Results

Participant Flow

Arm/Group Title	Iovera° Treatment	Sham Treatment
Arm/Group Description	Treatment with the iovera° device administered by a trained investigator to treat knee pain.	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.
Period Title: Overall Study
STARTED	121	59
Per-Protocol Population	112	56
COMPLETED	107	55
NOT COMPLETED	14	4

Baseline Characteristics

Arm/Group Title	Iovera° Treatment	Sham Treatment	Total
Arm/Group Description	Treatment with the iovera° device administered by a trained investigator to treat knee pain.	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.	Total of all reporting groups
Overall Participants	121	59	180
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	60.7	61.3	61.0
Sex: Female, Male (Count of Participants)
Female	79 65.3%	40 67.8%	119 66.1%
Male	42 34.7%	19 32.2%	61 33.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.8%	0 0%	1 0.6%
Asian	1 0.8%	0 0%	1 0.6%
Native Hawaiian or Other Pacific Islander	0 0%	1 1.7%	1 0.6%
Black or African American	8 6.6%	8 13.6%	16 8.9%
White	110 90.9%	50 84.7%	160 88.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 0.8%	0 0%	1 0.6%
Region of Enrollment (participants) [Number]
United States	121 100%	59 100%	180 100%
Body Mass Index (BMI) (kg/m^2) [Median (Full Range) ]
Median (Full Range) [kg/m^2]	29.02	29.99	29.5

Outcome Measures

1. Primary Outcome

Title	Absolute Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale Score at Day 30
Description	The WOMAC is a tri-dimensional, disease-specific, patient-reported outcome measure. It consists of 24 questions [each question is presented in a numerical rating scale format with possible values between 0= No (best) to 10= Extreme (worst)] with 5 questions regarding pain [possible subscale score 0 to 50], 2 questions regarding stiffness [possible subscale score 0 to 20] and 17 questions regarding function difficulty [possible subscale score 0 to 170]. A negative change from Baseline indicates improvement. An Analysis of Covariance (ANCOVA) model was used for analyses.
Time Frame	Baseline to Day 30

Outcome Measure Data

Analysis Population Description

Per-protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.

Arm/Group Title	Iovera° Treatment	Sham Treatment
Arm/Group Description	Treatment with the iovera° device administered by a trained investigator to treat knee pain.	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.
Measure Participants	112	56
Least Squares Mean (Standard Error) [score on a scale]	-16.33 (1.15)	-8.79 (1.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Iovera° Treatment, Sham Treatment
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	P-values are obtained by fitting an ANCOVA model with treatment as factor and WOMAC baseline pain score as a covariate.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Squares (LS) Means
	Estimated Value	-7.53
	Confidence Interval	(2-Sided) 95%; -11.48 to -3.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS estimates are obtained by fitting an ANCOVA model with treatment as factor and WOMAC baseline pain score as a covariate.

2. Secondary Outcome

Title	Change From Baseline in Visual Analog Scale (VAS) at Day 30
Description	VAS pain assessment is a measure of pain intensity. The scale is made up of a 10 centimeter (cm) [100 millimeter (mm)] horizontal line. The far left of the horizontal line is labeled "no pain" while the far right of the horizontal line is labeled "worst imaginable pain". A negative change from Baseline indicates improvement. An ANCOVA model was used for analyses.
Time Frame	Baseline to Day 30

Outcome Measure Data

Analysis Population Description

Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.

Arm/Group Title	Iovera° Treatment	Sham Treatment
Arm/Group Description	Treatment with the iovera° device administered by a trained investigator to treat knee pain.	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.
Measure Participants	112	56
Least Squares Mean (Standard Error) [score on a scale]	-39.20 (2.74)	-25.70 (3.89)

3. Secondary Outcome

Title	Change From Baseline in Total WOMAC Score at Day 30
Description	The WOMAC is a tri-dimensional, disease-specific, patient-reported outcome measure. It consists of 24 questions [each question is presented in a numerical rating scale format with possible values between 0= No (best) to 10= Extreme (worst)] with 5 questions regarding pain [possible subscale score 0 to 50], 2 questions regarding stiffness [possible subscale score 0 to 20] and 17 questions regarding function difficulty [possible subscale score 0 to 170]. The WOMAC total score was calculated by summing the 3 subscales for a total possible score of 0 to 240. A negative change from Baseline indicates improvement. An ANCOVA model was used for analyses.
Time Frame	Baseline to Day 30

Outcome Measure Data

Analysis Population Description

Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.

Arm/Group Title	Iovera° Treatment	Sham Treatment
Arm/Group Description	Treatment with the iovera° device administered by a trained investigator to treat knee pain.	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.
Measure Participants	112	56
Least Squares Mean (Standard Error) [score on a scale]	-77.18 (5.38)	-43.77 (7.61)

4. Secondary Outcome

Title	Change From Baseline in VAS at Day 60
Description	VAS pain assessment is a measure of pain intensity. The scale is made up of a 10 cm (100 mm) horizontal line. The far left of the horizontal line is labeled "no pain" while the far right of the horizontal line is labeled "worst imaginable pain". A negative change from Baseline indicates improvement. An ANCOVA model was used for analyses.
Time Frame	Baseline to Day 60

Outcome Measure Data

Analysis Population Description

Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.

Arm/Group Title	Iovera° Treatment	Sham Treatment
Arm/Group Description	Treatment with the iovera° device administered by a trained investigator to treat knee pain.	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.
Measure Participants	112	56
Least Squares Mean (Standard Error) [score on a scale]	-37.46 (2.80)	-28.82 (3.97)

5. Secondary Outcome

Title	WOMAC Pain Score Responder Rate at Day 30
Description	WOMAC Pain Score Responder Rate is defined as the percentage of participants with at least a 30% reduction in the WOMAC pain score at Day 30 compared to Baseline. WOMAC is a tri-dimensional, disease-specific, patient-reported outcome measure. It consists of 24 questions [each question is presented in a numerical rating scale format with possible values between 0= No to 10= Extreme] with the first 5 questions regarding pain [possible subscale score 0 (best) to 50 (worst)].
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.

Arm/Group Title	Iovera° Treatment	Sham Treatment
Arm/Group Description	Treatment with the iovera° device administered by a trained investigator to treat knee pain.	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.
Measure Participants	112	56
Number [percentage of participants]	67.9 56.1%	44.6 75.6%

6. Secondary Outcome

Title	VAS Responder Rate at Day 30
Description	VAS Responder Rate is defined as the percentage of participants with at least a 30% reduction in VAS at Day 30 compared to Baseline VAS pain assessment is a measure of pain intensity. The scale is made up of a 10 cm (100 mm) horizontal line. The far left of the horizontal line is labeled "no pain" while the far right of the horizontal line is labeled "worst imaginable pain".
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.

Arm/Group Title	Iovera° Treatment	Sham Treatment
Arm/Group Description	Treatment with the iovera° device administered by a trained investigator to treat knee pain.	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.
Measure Participants	112	56
Number [percentage of participants]	67.9 56.1%	48.2 81.7%

7. Secondary Outcome

Title	Change From Baseline in Total WOMAC Score at Day 60
Description	The WOMAC is a tri-dimensional, disease-specific, patient-reported outcome measure. It consists of 24 questions [each question is presented in a numerical rating scale format with possible values between 0= No (best) to 10= Extreme (worst)] with 5 questions regarding pain [possible subscale score 0 to 50], 2 questions regarding stiffness [possible subscale score 0 to 20] and 17 questions regarding function difficulty [possible subscale score 0 to 170]. The WOMAC total score was calculated by summing the 3 subscales for a total possible score of 0 to 240. A negative change from Baseline indicates improvement.
Time Frame	Baseline to Day 60

Outcome Measure Data

Analysis Population Description

Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.

Arm/Group Title	Iovera° Treatment	Sham Treatment
Arm/Group Description	Treatment with the iovera° device administered by a trained investigator to treat knee pain.	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.
Measure Participants	112	56
Least Squares Mean (Standard Error) [score on a scale]	-70.50 (5.52)	-49.99 (7.81)

8. Secondary Outcome

Title	VAS Responder Rate at Day 60
Description	VAS Responder Rate is defined as the percentage of participants with at least a 30% reduction in VAS at Day 60 compared to Baseline. VAS pain assessment is a measure of pain intensity. The scale is made up of a 10 cm (100 mm) horizontal line. The far left of the horizontal line is labeled "no pain" while the far right of the horizontal line is labeled "worst imaginable pain".
Time Frame	Day 60

Outcome Measure Data

Analysis Population Description

Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.

Arm/Group Title	Iovera° Treatment	Sham Treatment
Arm/Group Description	Treatment with the iovera° device administered by a trained investigator to treat knee pain.	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.
Measure Participants	112	56
Number [percentage of participants]	65.2 53.9%	55.4 93.9%

9. Secondary Outcome

Title	WOMAC Pain Score Responder Rate at Day 60
Description	WOMAC Pain Score Responder Rate is defined as the percentage of participants with at least a 30% reduction in the WOMAC pain score at Day 60 compared to Baseline. WOMAC is a tri-dimensional, disease-specific, patient-reported outcome measure. It consists of 24 questions [each question is presented in a numerical rating scale format with possible values between 0= No (best) to 10= Extreme (worst)] with the first 5 questions regarding pain [possible subscale score 0 to 50].
Time Frame	Day 60

Outcome Measure Data

Analysis Population Description

Per-Protocol Analysis Population included all participants who were randomized and underwent the assigned treatment where the treatment was successfully delivered as intended by the device and who are compliant with wash-out of pain medication prior to Baseline visit prior to study visit analyzed.

Arm/Group Title	Iovera° Treatment	Sham Treatment
Arm/Group Description	Treatment with the iovera° device administered by a trained investigator to treat knee pain.	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.
Measure Participants	112	56
Number [percentage of participants]	64.3 53.1%	48.2 81.7%

Adverse Events

Time Frame	6 Months
Adverse Event Reporting Description	Adverse Event (AE) data was collected over a 6 month period. Patients were followed until AE's were resolved.
Arm/Group Title	Iovera° Treatment		Sham Treatment
Arm/Group Description	Treatment with the iovera° device administered by a trained investigator to treat knee pain.		Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.
All Cause Mortality
	Iovera° Treatment		Sham Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/121 (0.8%)		0/59 (0%)
Serious Adverse Events
	Iovera° Treatment		Sham Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/121 (1.7%)		1/59 (1.7%)
Cardiac disorders
Myocardial infarction	1/121 (0.8%)		0/59 (0%)
Acute myocardial infarction	1/121 (0.8%)		0/59 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant	1/121 (0.8%)		0/59 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/121 (0%)		1/59 (1.7%)
Other (Not Including Serious) Adverse Events
	Iovera° Treatment		Sham Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	121/121 (100%)		59/59 (100%)
Skin and subcutaneous tissue disorders
Administration site bruise	93/121 (76.9%)		31/59 (52.5%)
Administration site dysaesthesia	25/121 (20.7%)		11/59 (18.6%)
Administration site pain	26/121 (21.5%)		11/59 (18.6%)
Administration site paraesthesia	17/121 (14%)		2/59 (3.4%)
Administration site scab	6/121 (5%)		3/59 (5.1%)
Administration site swelling	49/121 (40.5%)		16/59 (27.1%)
Application site discolouration	1/121 (0.8%)		0/59 (0%)
Application site pruritus	7/121 (5.8%)		2/59 (3.4%)
Application site hypoaesthesia	63/121 (52.1%)		32/59 (54.2%)
Application site erythema	50/121 (41.3%)		24/59 (40.7%)
Application site pain	46/121 (38%)		23/59 (39%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.