Cooled Radiofrequency vs. Hyaluronic Acid to Manage Knee Pain

A Prospective, Multi-center, Randomized, Clinical Trial Evaluating the Safety and Effectiveness of Using COOLIEF™ Cooled Radiofrequency Probe to Create Lesions of the Genicular Nerves and Comparing a Single Injection of Hyaluronic Acid in the Management of Knee Pain

This is a prospective, randomized, multicenter comparison study examining the outcomes of subjects with osteoarthritis and knee pain undergoing a procedure to create a radiofrequency lesion of the genicular nerves with the Cooled Radiofrequency Ablation (CRFA) system compared to subjects receiving Hyaluronic Acid (HA). Approximately 168 subjects will be enrolled into this study, with subjects undergoing either CRFA or HA injection in a 1:1 randomization scheme. Follow-up will be conducted for 12 months post-CRFA, with the primary endpoint being completed at month 6. Subjects randomized to the comparison (HA) group will have the option to cross-over to the neurotomy group after completing the 6-month endpoint assessment. They will be followed for an additional 6 months. Pain, overall outcome, quality of life, pain medication use, and adverse events will be compared between the two treatment groups to determine success. Subjects who were randomized to and received COOLIEF* as their initial treatment will have the option to add 2 additional visits at 6-month intervals, representing 18 and 24 months post initial treatment.

The COOLIEF™ system components utilized in the study are the same in form and function regardless of specific product branding (COOLIEF* or SInergy*). The COOLIEF™ system is comprised of three primary components (collectively known as 'disposables') and is used in conjunction with the Pain Management generator, pump unit, connector cables (collectively known as 'Hardware') and dispersive electrodes (also known as 'grounding pads'):

• Cooled Radiofrequency Sterile Tube Kit (sterile, single use, non-body contact): It is used for closed-loop circulation of sterile water through a Halyard Health* Cooled Radiofrequency Probe. It includes a burette and tubing.
• Cooled Radiofrequency Introducer (sterile, single use): It is to be used with the Probes only. The Cooled Radiofrequency Introducer provides a path for the Probe to the targeted nervous tissue.
• Cooled Radiofrequency Probe (sterile, single use): It is inserted through an Introducer into or near nervous tissue. The active tip extends 4mm from the introducer and delivers energy. Sterile water circulates internally to cool the Probe while it delivers radiofrequency energy. A thermocouple in the Probe measures the cooled electrode temperature throughout the procedure.

The product is comprised of an electrically insulated shaft with an active tip that functions as an electrode for radiofrequency energy delivery, a handle, tubes with luer locks and a cable with a 7-pin connector. The Introducer includes an insulated stainless steel cannula and a stylet. The Tube Kit is comprised of a burette and flexible tubing fitted with luer locks for connection to the Probe. The Probe, Introducer, and Tube Kit are ethylene oxide sterilized and supplied sterile. These components can be packaged together in a kit or as separate components. The devices should be stored in a cool, dry environment. The Instructions For Use (IFU) documents (Appendix 1) are included in each kit.

Halyard Health maintains a list of all model numbers and sizes for the system components.

The control product/device, Synvisc-One® (hylan G-F 20) (HA), is an elastoviscous high molecular weight fluid containing hylan A and hylan B polymers produced from chicken combs. Hylans are derivatives of hyaluronan (sodium hyaluronate). Hylan G-F 20 is unique in that the hyaluronan is chemically crosslinked. Hyaluronan is a long-chain polymer containing repeating disaccharide units of Na-glucuronate-N-acetylglucosamine.

Synvisc-One is a single injection regimen therapy indicated for the treatment of pain in Osteoarthritis of the knee in patients who have failed to respond adequately to conservative nonpharmacologic therapy and simple analgesics, e.g., acetaminophen.

Following treatment, subjects in the CRF treatment group will follow up at 1, 3, 6 and 12 months. These subjects will then have the option to return for two additional visits at 18 and 24 months. Subjects initially randomized to the comparison (HA) group will follow up at 1, 3, and 6 months, and then be given the option to receive crossover CRF treatment. If crossover CRF treatment was received, subjects will return for follow up visits at 1, 3, and 6 months post-treatment. If crossover treatment was not received, subjects will return for their final 12 month visit.

Study Duration:

• Treatment Group: Up to 24 months following index procedure
• Control Group: Up to 13 months, depending upon receipt of cross-over procedure.

Effectiveness Endpoints:

• Numeric Rating Scale (NRS, Usual Level of Pain)
• Western Ontario & McMaster University Osteoarthritis Index (WOMAC)
• EQ-5D-5L Health-Related Quality of Life Questionnaire
• Global Perceived Effect Scale

INCLUSION CRITERIA

1. Age ≥ 21 years
2. Able to understand the informed consent form and provide written informed consent and able to complete outcome measures
3. Chronic knee pain for longer than 6 months that interferes with functional activities (for example, ambulation, prolonged standing, etc.)
4. Continued pain in the target knee despite at least 3 months of conservative treatments, including activity modification, home exercise, protective weight bearing, and/or analgesics (for example, acetaminophen or non-steroidal anti-inflammatory drugs [NSAIDs])
5. Positive response (defined as a decrease in numeric pain scores of at least 50%) to a single genicular nerve block of the index knee
6. Pain on NRS ≥ 6 on an 11-point scale for the index knee
7. Radiologic confirmation of arthritis (x-ray/MRI/CT) of Osteoarthritis (OA) grade of 2 (mild), 3 (moderate) or 4 (severe) noted within 6 months for the index knee
8. An intra-articular hyaluronic acid injection is indicated as an appropriate treatment option
9. WOMAC Knee Score group at baseline of Score of ≥ 2 (0 to 4 scale) on WOMAC question 1 (Pain) and a mean score of ≥ 1.5 on all five questions of the WOMAC pain subscale.
10. Analgesics including membrane stabilizers such as Neurontin/gabapentin and antidepressants for pain such as Cymbalta/duloxetine must be clinically stable (defined as stable dosage for ≥ 6 weeks prior to the screening visit) and shall not change during the course of the study without approval of the investigator
11. Agree to see one physician (study physician) for knee pain during the study period
12. Willing to utilize double barrier contraceptive method if of child bearing potential.
13. Willing to delay any surgical intervention for the index knee for the period of the study follow up
14. Willingness to provide informed consent and to comply with the requirements of this protocol for the full duration of the study

EXCLUSION CRITERIA

1. Evidence of inflammatory arthritis (for example, rheumatoid arthritis) or other systemic inflammatory condition (for example, gout, fibromyalgia) that could cause knee pain
2. Evidence of neuropathic pain affecting the index knee
3. Previous or pending lower limb amputation
4. Intra-articular steroid injection into the index knee within 90 days from randomization
5. Hyaluronic acid injection, platelet rich plasma (PRP), stem cell, or arthroscopic debridement/lavage injection into the index knee within 180 days from randomization
6. Prior radiofrequency ablation of the genicular nerves of the index knee
7. Prior partial, resurfacing, or total knee arthroplasty of the index knee (residual hardware)
8. Clinically significant ligamentous laxity of the index knee
9. Clinically significant valgus/varus deformities or evidence of pathology (other than osteoarthritis of knee) that materially affects gait or function of the knee or is the underlying cause of the knee pain and/or functional limitations
10. Body mass index (BMI) > 40 kg/m2
11. Extremely thin patients and those with minimal subcutaneous tissue thickness that would not accommodate a radiofrequency lesion of up to 14 mm in diameter to limit the risk of skin burns
12. Pending or active compensation claim, litigation or disability remuneration (secondary gain)
13. Pregnant, nursing or intent on becoming pregnant during the study period
14. Chronic pain associated with significant psychosocial dysfunction
15. Beck's Depression Index score of > 22 (indicates clinically depressed state)
16. Allergies to any of the medications to be used during the procedures, including known hypersensitivity (allergy) to hyaluronate preparations or allergies to avian or avian-derived products (including eggs, feathers, or poultry)
17. Active joint infection or systemic or localized infection at needle entry sites (subject may be considered for inclusion once infection is resolved)
18. History of uncontrolled coagulopathy, ongoing coagulation treatment that cannot be safely interrupted for procedure, or unexplained or uncontrollable bleeding that is uncorrectable.
19. Identifiable anatomical variability that would materially alter the procedure as described in the protocol
20. Within the preceding 2 years, subject has suffered from active narcotic addiction, substance, or alcohol abuse
21. Current prescribed opioid medications greater than 60 morphine equivalent daily opioid dose
22. Uncontrolled immunosuppression (e.g. AIDS, cancer, diabetes, etc.)
23. Subject currently implanted with pacemaker, stimulator or defibrillator.
24. Participating in another clinical trial/investigation within 30 days prior to signing informed consent
25. Subject unwilling or unable to comply with follow up schedule or protocol requirements