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

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

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.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Device: iovera°; Device: Sham Comparator

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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 Outcome Measures

Outcome Measure	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.	Baseline to Day 30
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.	Baseline to Day 30
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.	Baseline to Day 60
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)].	Day 30
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".	Day 30
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.	Baseline to Day 60
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".	Day 60
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].	Day 60

Collaborators and Investigators

• Sponsor: Pacira Pharmaceuticals, Inc

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2014
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): May 31, 2016

Study Registration Dates

• First Submitted: October 3, 2014
• First Submitted That Met QC Criteria: October 6, 2014
• First Posted (Estimated): October 9, 2014

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: MYO-0946

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes