Study to Evaluate the Iovera° Device for Temporary Relief... | NCT02260921

Status Module

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

Name	Type	Description	Arm Group Labels	Other Names
iovera°	Device		iovera° Treatment
Sham Comparator

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Absolute Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale Score at 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.	Baseline to Day 30

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Visual Analog Scale (VAS) at 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.

Eligibility Module

Eligibility Criteria

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.

Facility	Status	City	State	ZIP	Country	Contacts
Medvin Clinical Research		Covina	California	91723	United States
UC Davis Center for Musculoskeletal Health

PubMed Identifier	Type	Citation	Retractions
28336454	Derived	Radnovich 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.

ID	Title	Description
FG000	Iovera° Treatment	Treatment with the iovera° device administered by a trained investigator to treat knee pain.
FG001	Sham Treatment	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.

ID	Title	Description
BG000	Iovera° Treatment	Treatment with the iovera° device administered by a trained investigator to treat knee pain.
BG001	Sham Treatment	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000121 BG00159 BG002180

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Absolute Change From Baseline in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale Score at 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.

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.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline to Day 30

ID	Title	Description
OG000	Iovera° Treatment	Treatment with the iovera° device administered by a trained investigator to treat knee pain.
OG001	Sham Treatment	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.

Units	Counts
Participants	OG000112 OG00156

Title

Denominators

Categories

Title	Measurements
	OG000-16.33± 1.15 OG001-8.79± 1.63

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		0.0002	P-values are obtained by fitting an ANCOVA model with treatment as factor and WOMAC baseline pain score as a covariate.	Difference in Least Squares (LS) Means	-7.53			2-Sided	95	-11.48	-3.58			LS estimates are obtained by fitting an ANCOVA model with treatment as factor and WOMAC baseline pain score as a covariate.		Superiority

Secondary

Change From Baseline in Visual Analog Scale (VAS) at 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.

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.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline to Day 30

ID	Title	Description
OG000	Iovera° Treatment	Treatment with the iovera° device administered by a trained investigator to treat knee pain.
OG001	Sham Treatment	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.

Units	Counts
Participants

Secondary

Change From Baseline in Total WOMAC Score at 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.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline to Day 30

ID	Title	Description
OG000	Iovera° Treatment	Treatment with the iovera° device administered by a trained investigator to treat knee pain.
OG001	Sham Treatment	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.

Secondary

Change From Baseline in VAS at 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.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline to Day 60

ID	Title	Description
OG000	Iovera° Treatment	Treatment with the iovera° device administered by a trained investigator to treat knee pain.
OG001	Sham Treatment	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.

Units	Counts
Participants

Secondary

WOMAC Pain Score Responder Rate at 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)].

Posted

Number

percentage of participants

Day 30

ID	Title	Description
OG000	Iovera° Treatment	Treatment with the iovera° device administered by a trained investigator to treat knee pain.
OG001	Sham Treatment	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.

Units	Counts

Secondary

VAS Responder Rate at 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".

Posted

Number

percentage of participants

Day 30

ID	Title	Description
OG000	Iovera° Treatment	Treatment with the iovera° device administered by a trained investigator to treat knee pain.
OG001	Sham Treatment	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.

Units	Counts
Participants

Secondary

Change From Baseline in Total WOMAC Score at 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.

Posted

Least Squares Mean

Standard Error

score on a scale

Baseline to Day 60

ID	Title	Description
OG000	Iovera° Treatment	Treatment with the iovera° device administered by a trained investigator to treat knee pain.
OG001	Sham Treatment	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.

Secondary

VAS Responder Rate at 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".

Posted

Number

percentage of participants

Day 60

ID	Title	Description
OG000	Iovera° Treatment	Treatment with the iovera° device administered by a trained investigator to treat knee pain.
OG001	Sham Treatment	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.

Units	Counts
Participants

Secondary

WOMAC Pain Score Responder Rate at 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].

Posted

Number

percentage of participants

Day 60

ID	Title	Description
OG000	Iovera° Treatment	Treatment with the iovera° device administered by a trained investigator to treat knee pain.
OG001	Sham Treatment	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.

Units	Counts

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Administration site bruise	Skin and subcutaneous tissue disorders	MedDRA LLT	Systematic Assessment	EG00093 affected121 at risk EG00131 affected59 at risk
Administration site dysaesthesia	Skin and subcutaneous tissue disorders	MedDRA LLT	Systematic Assessment	EG00025 affected121 at risk EG00111 affected59 at risk
Administration site pain	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG00026 affected121 at risk EG00111 affected59 at risk
Administration site paraesthesia	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG00017 affected121 at risk EG0012 affected59 at risk
Administration site scab	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0006 affected121 at risk EG0013 affected59 at risk
Administration site swelling	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG00049 affected121 at risk EG00116 affected59 at risk
Application site discolouration	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0001 affected121 at risk EG0010 affected59 at risk
Application site pruritus	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG0007 affected121 at risk EG0012 affected59 at risk
Application site hypoaesthesia	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG00063 affected121 at risk EG00132 affected59 at risk
Application site erythema	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG00050 affected121 at risk EG00124 affected59 at risk
Application site pain	Skin and subcutaneous tissue disorders	MedDRA	Systematic Assessment	EG00046 affected121 at risk EG00123 affected59 at risk

ID	Term
D010003	Osteoarthritis
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Iovera° Treatment	Treatment with the iovera° device administered by a trained investigator to treat knee pain.	1	121	2	121	121	121
EG001	Sham Treatment	Sham Treatment (similar device with no active therapeutic treatment) administered by a trained investigator to treat knee pain.	0	59	1	59	59	59

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Myocardial infarction	Cardiac disorders	MedDRA LLT	Systematic Assessment	EG0001 affected121 at risk EG0010 affected59 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected121 at risk EG0010 affected59 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected121 at risk EG0011 affected59 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA	Systematic Assessment	EG0001 affected121 at risk EG0010 affected59 at risk