Cooled Radiofrequency vs. Hyaluronic Acid to Manage Knee Pain

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 RF 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 OA
of the knee in patients who have failed to respond adequately to conservative
nonpharmacologic therapy and simple analgesics, e.g., acetaminophen.

Study Duration:

- Overall Study: Estimated 24-30 months

- Individual Study Participation: Up to 13 months post-treatment

- Treatment Group: Up to 12 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 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