Coolief* Cooled RF Probe

K163461 · Halyard Health, Inc. · GXI · Apr 13, 2017 · Neurology

Device Facts

• Record ID: K163461
• Device Name: Coolief* Cooled RF Probe
• Applicant: Halyard Health, Inc.
• Product Code: GXI · Neurology
• Decision Date: Apr 13, 2017
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 882.4725
• Device Class: Class 2
• Attributes: Therapeutic

Intended Use

The COOLIEF* Cooled Radiofrequency Probe is to be used in conjunction with a radiofrequency generator to create lesions in nervous tissue. This device is also indicated for creating radiofrequency lesions of the genicular nerves for the management of moderate to severe knee pain of more than 6 months with conservative therapy, including medication, in patients with radiologically-confirmed osteoarthritis (grade 2-4) and a positive response (≥50% reduction in pain) to a diagnostic genicular nerve block.

Device Story

COOLIEF* Cooled RF Probe is a sterile, single-use device for creating lesions in nervous tissue. Input: RF energy delivered via probe tip; cooling provided by circulating sterile water. Transformation: Internal water circulation cools electrode tip during ablation, enabling larger, more homogeneous RF heating area in target tissue. Output: RF lesions in nervous tissue. Used in clinical settings by physicians; device connects to Halyard RF Generator. Healthcare providers use output to perform genicular neurotomy; procedure blocks pain signal transmission. Benefits: Provides sustained pain reduction and functional improvement for patients with chronic knee osteoarthritis.

Clinical Evidence

Prospective, multicenter, randomized comparative study (n=151). Primary endpoint: ≥50% knee pain reduction (NRS) at 6 months. Results: 67.2% success in COOLIEF group vs 15.7% in corticosteroid injection group. Mean NRS drop: 4.9 points (COOLIEF) vs 1.3 points (control). Functional improvement: 39.7% (COOLIEF) vs 3% (control). Adverse events were similar between groups; no significant safety concerns identified.

Technological Characteristics

Sterile, single-use RF probe. Materials: Polyimide-insulated shaft, medical-grade stainless steel electrode. Sensing: Thermocouple (accuracy ±3°C). Energy: RF (38°-95°C). Dimensions: 18Ga shaft, 50-150mm length. Cooling: Internal circulating sterile water. Sterilization: Ethylene oxide (SAL 10^-6). Compliance: IEC 60601-1, IEC 60601-2-2, IEC 60601-1-2.

Indications for Use

Indicated for patients with moderate to severe knee pain (>6 months) refractory to conservative therapy, including medication, with radiologically-confirmed osteoarthritis (grade 2-4) and a positive response (≥50% reduction in pain) to a diagnostic genicular nerve block.

Regulatory Classification

Identification

A radiofrequency lesion probe is a device connected to a radiofrequency (RF) lesion generator to deliver the RF energy to the site within the nervous system where a lesion is desired.

Predicate Devices

• Pain Management Cooled Probe (K053082)

Reference Devices

• TransDiscal* RF probe (K031951)

Submission Summary (Full Text)

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

April 13, 2017

Halyard Health, Inc. Monica King Associate Director, Regulatory Affairs 5405 Windward Parkway Alpharetta, Georgia 30004

Re: K163461

Trade/Device Name: Coolief* Cooled RF Probe Regulation Number: 21 CFR 882.4725 Regulation Name: Radiofrequency Lesion Probe Regulatory Class: Class II Product Code: GXI Dated: March 13, 2017 Received: March 14, 2017

Dear Ms. King:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices. good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical devicerelated adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely,

# Michael J. Hoffmann -S

Carlos L. Peña, PhD, MS for Director Division of Neurological and Physical Medicine Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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## Indications for Use

510(k) Number (if known) K163461

Device Name COOLIEF* Cooled RF Probe

#### Indications for Use (Describe)

The COOLIEF* Cooled Radiofrequency Probe is to be used in conjunction with a radiofrequency generator to create lesions in nervous tissue. This device is also indicated for creating radiofrequency lessons of the management of moderate to severe knee pain of more than 6 months with conservative therapy, including medication, in patients with radiologically-confirmed osteoarthritis (grade 2-4) and a possitive response (≥50% reduction in pain) to a diagnostic genicular nerve block.

| Type of Use (Select one or both, as applicable) | |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------|
| <span style="font-family: Arial;"> <span style="font-size: 10pt;"> <span style="font-style: normal;"> <span style="font-variant: normal;"> <span style="font-weight: normal;"> <span style="letter-spacing: normal;"> <span style="line-height: normal;"> <span style="orphans: auto;"> <span style="text-align: start;"> <span style="text-indent: 0px;"> <span style="text-transform: none;"> <span style="white-space: normal;"> <span style="widows: auto;"> <span style="word-spacing: 0px;"> <span style="-webkit-text-stroke-width: 0px;"> <input checked="true" type="checkbox"/> Prescription Use (Part 21 CFR 801 Subpart D) </span> </span> </span> </span> </span> </span> </span> </span> </span> </span> </span> </span> </span> </span> </span> | <input type="checkbox"/> Over-The-Counter Use (21 CFR 801 Subpart C) |

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# 510(k) Summary as Required by 21 CFR §807.92(c)

As required by the Safe Medical Devices Act (SMDA) of 1990 and in accordance with 21 CFR §807.92(a), the 510(k)-summary provided below is of sufficient detail to provide an understanding of the basis for a determination of substantial equivalence.

# 510(k) Summary

#### 1. Contact Details

| Date Summary Prepared | 04/05/2017 |
|-----------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------|
| 510(k) Applicant Name,<br>Address,<br>Website | Halyard Health, Inc.<br>5405 Windward Parkway<br>Alpharetta, GA 30004<br>www.halyardhealth.com |
| Applicant Contact Person | Monica King<br>Associate Director, Regulatory Affairs<br>Phone: [phone]<br>FAX: [phone]<br>Email: [e-mail] |

## 2. Device Information

| Trade Name | COOLIEF* Cooled RF Probe |
|---------------------|------------------------------|
| Common Name | Radiofrequency Lesion Probe |
| Models | CRP-, CRK-, MCK- |
| Classification | II |
| Classification Name | Probe, Radiofrequency Lesion |
| Regulation Number | 21 CFR §882.4725 |
| Product Code | GXI |
| Review Panel | 84 Neurology |

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#### 3. Legally Marketed Predicate Device:

| Trade Name | Pain Management Cooled Probe |
|---------------|------------------------------|
| 510(k) Number | K053082 |
| Product Code | GXI |
| Manufacturer | Halyard Health |

#### 4. Description of Device:

The COOLIEF* Cooled Radiofrequency (RF) Probe is a sterile, single-use device that delivers RF energy within the area of the active probe tip, while the probe tip is cooled by sterile water that circulates within the probe. Cooling the probe tip creates a larger. more homogenous RF heating area that results in a larger RF lesion in the target tissue. COOLIEF* Cooled RF Probe is used in conjunction with the Halyard RF Generator to create RF lesions in nervous tissue. The shaft of the probe is insulated with a polyimide sheath, and the distal tip consists of a medical grade stainless steel electrode. Sterile water circulates through a cavity in the electrode to cool the electrode tip during the cooled RF ablation procedure. The COOLIEF* Cooled Radiofrequency (RF) Probe is sterilized by ethylene oxide.

## Proposed Indication for Use:

The COOLIEF* Cooled Radiofrequency Probe is to be used in conjunction with a radiofrequency generator to create lesions in nervous tissue. This device is also indicated for creating radiofrequency lesions of the genicular nerves for the management of moderate to severe knee pain of more than 6 months with conservative therapy, including medication, in patients with radiologicallyconfirmed osteoarthritis (grade 2-4) and a positive response (≥50% reduction in pain) to a diagnostic genicular nerve block.

## 5. Substantial Equivalence Comparison

The following table compares the subject COOLIEF* Cooled RF Probe to the predicate Pain Management Cooled Probe (K053082) to support substantial equivalence.

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| Characteristic | COOLIEF*<br>Cooled RF<br>Probe<br>(K163461) | Pain<br>Management<br>Cooled Probe<br>(K053082) | Comments |
|----------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The COOLIEF* Cooled<br>Radiofrequency Probe is to<br>be used in conjunction<br>with a radiofrequency<br>generator to create lesions<br>in nervous tissue. This<br>device is also indicated for<br>creating radiofrequency<br>lesions of the genicular<br>nerves for the management<br>of moderate to severe knee<br>pain of more than 6<br>months with conservative<br>therapy, including<br>medication, in patients<br>with radiologically-<br>confirmed osteoarthritis<br>(grade 2-4) and a positive<br>response (≥50% reduction<br>in pain) to a diagnostic<br>genicular nerve block. | Used in conjunction<br>with a radiofrequency<br>generator to create<br>radiofrequency lesions<br>in nervous tissue. | Clinical data to support the<br>proposed indication is<br>submitted in the Protocol A<br>Prospective, Multi-center,<br>Randomized, Clinical Trial<br>Evaluating the Safety and<br>Effectiveness of Using<br>Coolief™ Cooled<br>Radiofrequency Probe to<br>Create Lesions of the<br>Genicular Nerves and<br>Comparing Corticosteroid<br>Injection in the Management<br>of Knee Pain |
| Probe Shaft<br>Length | Overall Useable Length<br>150mm, 100mm, 75mm,<br>50mm<br>Shaft Outer Diameter<br>18Ga | Overall Useable Length<br>150mm, 100mm, 75mm,<br>50mm<br>Shaft Outer Diameter<br>18Ga | Equivalent |
| Distal Tip<br>Length | 6mm probe electrode<br>with various active<br>lengths when combined<br>with a mating introducer<br>of 2, 4, and 5.5mm | 6mm probe electrode<br>with various active<br>lengths when combined<br>with a mating introducer<br>of 2, 4, and 5.5mm | Equivalent |
| Lesion Size | 10-12mm,<br>Spherical | 10-12mm,<br>Spherical | Equivalent |
| Temperature<br>Measurement<br>Accuracy | ± 3° C | ± 3° C | Equivalent |
| Temperature<br>Measurement<br>Device | Thermocouple | Thermocouple | Equivalent |
| Characteristic | COOLIEF*<br>Cooled RF<br>Probe<br>(K163461) | Pain Management<br>Cooled Probe<br>(K053082) | Comments |
| Temperature<br>Range | 38° - 95° C | 38° - 95° C | Equivalent |
| Temperature<br>Increment | 1°C | 1°C | Equivalent |
| Single Use | Yes | Yes | Equivalent |
| Compatible RF<br>System | Halyard<br>COOLIEF*<br>System Only | Halyard<br>COOLIEF*<br>System Only | Equivalent |
| Disposable | Yes | Yes | Equivalent |
| Biocompatibility | Conforms to<br>ISO10993 | Conforms to<br>ISO10993 | Equivalent |
| Sensitization<br>ISO 10993-10 | Conforms to<br>ISO10993-10 | Conforms to<br>ISO10993-<br>10 | Equivalent |
| Irritation<br>ISO 10993-20 | Conforms to<br>ISO10993-20 | Conforms to<br>ISO10993-<br>20 | Equivalent |
| Cytotoxicity<br>ISO 10993-5 | Conforms to<br>ISO10993-5 | Conforms<br>to<br>ISO10993-5 | Equivalent |
| Characteristic | COOLIEF*<br>Cooled RF<br>Probe<br>(K163461) | Pain Management<br>Cooled Probe<br>(K053082) | Comments |
| Systemic<br>toxicity<br>ISO 10993-11 | Conforms to<br>ISO10993-11 | Conforms to<br>ISO10993-11 | Equivalent |
| Sterility | Sterilized by EO<br>SAL = 10-6 | Sterilized by EO<br>SAL = 10-6 | Equivalent |
| Packaging | Device contained in a<br>single use Tyvek sealed<br>tray | Device contained in a<br>single use Tyvek sealed<br>tray | Equivalent |

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The difference in the Indications for Use statements do not raise new questions of safety and effectiveness. Cooled radiofrequency (RF) is a well-established method for delivering lesions into nervous tissue to accomplish neurotomy procedures. The use of the Cooled RF probe to perform the genicular neurotomy procedure is like the other minimally invasive cooled radiofrequency ablation procedures in that lesions are created in targeted sensory nerves to block the transmission of pain signals. The RF lesions created in the genicular neurotomy procedure are the same size and shape as in other RF procedures. The clinical data collected to support the proposed indication demonstrate that the COOLIEF* Cooled RF Probe does not present safety or effectiveness issues related to the proposed indication for use. Data collected at the primary endpoint supports the conclusion that the COOLIEF* Cooled RF Probe used for genicular nerve ablation is superior to corticosteroid injection in osteoarthritic subjects for managing knee pain.

#### Reference Device

A reference device is presented below regarding the biocompatibility data set for this device. Biocompatibility testing data is derived from testing conducted on the representative Halyard* TransDiscal* RF probe (K031951): the TransDiscal* RF probe and the Cooled Radiofrequency Probe are composed of the same raw materials, manufactured using similar processes within the same facility, sterilized using the same Ethylene Oxide cycles and chambers, and packaged using the same packaging materials.

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| Comparison to Reference Device | |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Subject Device: COOLIEF* Cooled RF Probe | Reference Device: TransDiscal* RF probe |
| K163481 | K031951 |
| The COOLIEF* Cooled<br>Radiofrequency Probe is to be used in<br>conjunction with a radiofrequency<br>generator to create lesions in nervous<br>tissue. This device is also indicated<br>for creating radiofrequency lesions of<br>the genicular nerves for the<br>management of moderate to severe<br>knee pain of more than 6 months with<br>conservative therapy, including<br>medication, in patients with<br>radiologically-confirmed<br>osteoarthritis (grade 2-4) and a<br>positive response (≥50% reduction in<br>pain) to a diagnostic genicular nerve<br>block. | The Transdiscal system, in combination with<br>the Baylis Pain Management Generator-TD<br>(PMG-TD), is indicated for the coagulation and<br>decompression of disc material to treat<br>symptomatic patients with contained herniated<br>discs. |
| Sterility: Sterilized by | Sterility: Sterilized |
| EO SAL = 10-6 | by EO SAL = 10-6 |
| Packaging: Device contained in a single use<br>Tyvek sealed tray | Packaging: Device contained in a single use<br>Tyvek sealed tray |

# 6. Non-Clinical Testing

The table below describes the test type, standard reference, acceptance criteria, and result summary.

| Test Type | Standard | Test Name | Criteria | Result |
|-----------------------------------------------|--------------|----------------------------------------------|----------------------------------------------------------------------|-------------------------------------------|
| Cytotoxicity | ISO 10993-5 | In Vitro Cytotoxicity,<br>Direct and Extract | Qualitative Grade = 0<br>Quantitative = cell death<br>< 30% | Pass: No<br>Cytotoxic effect |
| Sensitization | ISO 10993-10 | In Vivo, Animal GPMT | Challenge Phase = Less<br>than Grade 1 and less<br>than the controls | Pass: No signs<br>of sensitization |
| Irritation or<br>Intracutaneous<br>reactivity | ISO 10993-10 | In Vivo, Animal<br>Irritation (Rabbits) | Test sample score < 1.0<br>for Erythema and Edema<br>grading | Pass: No signs<br>of Irritation |
| Systemic Toxicity<br>(acute) | ISO 10993-11 | In Vivo, Animal<br>Toxicity (Mice) | No animal death | Pass: No signs<br>of systemic<br>toxicity |

Biocompatibility Testing

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| Test | Test Description | Results |
|-------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------|
| Electrical safety | IEC 60601-1:2005<br>Medical electrical equipment<br>Part 1: General requirements for basic safety and essential performance | Passed |
| High Frequency surgical equipment | IEC 60601-2-2: 2009 (Fifth Ed.)<br>Medical electrical equipment<br>Part 2-2: Requirements for basic safety and essential performance of high frequency surgical equipment and high frequency surgical accessories | Passed |
| Electromagnetic Compatibility (EMC) | IEC 60601-1-2:2007 / AC 2010<br>Medical electrical equipment<br>Part 1-2: General requirements for safety –<br>Collateral standard: Electromagnetic compatibility | Passed |

#### Summary of IEC 60601 Compliance

#### 7. Clinical Testing

Halyard conducted a prospective, multicenter, randomized comparative human study, to confirm the safety and effectiveness of COOLIEF* Cooled RF Probe for creating lesions of the genicular nerves for pain management of the knee. The COOLIEF* Cooled RF Probe was compared to corticosteroid injection.

The primary effectiveness endpoint of the clinical study was the proportion of subjects whose knee pain is reduced by ≥ 50% based on the Numeric Rating Scale (NRS) at the 6month study time point. At the 6-month study time point, based on Intention to Treat (ITT) ≥50% pain relief over baseline was experienced by 67.2% of the COOLIEF* Cooled RF study group vs. 15.7% of the comparison group (i.e., corticosteroid injection), using the Numeric Rating Scale (Pain rating scale 1 to 10).

Significant and sustained pain reduction was observed in the study group: subjects had a 4.9-point mean drop in NRS from a baseline mean of 7.3 to a mean of 2.5 at 6 months, while the comparison group had a 1.3-point mean drop in NRS from a baseline of 7.2 to a mean of 5.9 at 6 months. Significant functional improvement occurred in the study group: 39.7% reported "Satisfactory Joint Function" vs. 3% in comparison group. Global Perceived Effect Knee condition was reported as "improved" in 91.4% of the study group vs. 23.9% in the comparison group.

#### Adverse Events

The proportion of study subjects that had adverse events (AEs) in each cohort was: CRFA, 45% (34/76); IAS, 40% (30/75). The number of AEs reported in each study group was similar (CRFA = 61 events, IAS = 65 events). Most AEs during the study were non-serious, mild or moderate in severity, and were determined to be not related to study treatment. The AEs with Possible, Probable, or Definite relationship to procedure are:

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- CRFA Group (14 events in 13 subjects): post-procedure pain (9 events), ecchymosis (1), pruritic skin lesion (1), swelling and redness - infection (1), mild tenderness to touch (1), increased knee pain - severe (1)
- IAS Group (2 events in 2 subjects): white discoloration at injection site (1), ● fluctuating blood sugar levels (1)
- Post-procedural "fall" incidence: ■
- CRFA Group (2 events in 1 subject) ●
- . IAS Group (4 events in 4 subjects)
- I Serious AEs:
- . CRFA Group (4 events in 2 subjects): 1) pyelonephritis, 2) exacerbation of asthma, 3) severe acute asthma, and 4) acute respiratory failure
- IAS Group (8 events in 7 subjects): 1) opioid overdose, 2) heart attack (two ● subjects), 3) death, 4) nausea and vomiting, 5) worsening of hiatal hernia, 6) gastric volvulus, and 7) abdominal pain secondary to small bowel obstruction.

## Medication Use

The study demonstrated a reduction in non-opioid pain medication that was consistent with the clinically relevant improvements demonstrated in the primary endpoint. Table 76 below describes the pain medication usage for subjects taking non-morphine medication at the baseline through 6 months' visits.

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| | Baseline | | 1 Month | | 3 Month | | 6 Month | |
|-------------------------------------------------------------------------------------------|----------------------|--------|---------------------|---------|---------------------|---------|----------------------|---------|
| | CRFA | IAS | CRFA | IAS | CRFA | IAS | CRFA | IAS |
| Non-Morphine Pain Medication<br>Usage - Total Daily Dose (mg) | | | | | | | | |
| N | 33 | 35 | 33 | 34 | 32 | 34 | 29 | 35 |
| Mean | 899.5 | 497.4 | 899.5 | 537.9 | 865.2 | 561.2 | 834.8 | 621.4 |
| SD | 625.1 | 437.3 | 625.1 | 484.4 | 636.4 | 461.4 | 682.0 | 497.5 |
| Median | 700.0 | 470.0 | 700.0 | 472.5 | 675.0 | 498.0 | 650.0 | 545.0 |
| Minimum | 150.0 | 0.0 | 150.0 | 0.0 | 150.0 | 0.0 | 0.0 | 0.0 |
| Maximum | 3000.0 | 2000.0 | 3000.0 | 2000.0 | 3000.0 | 2000.0 | 3000.0 | 2000.0 |
| Difference between means<br>(CRFA-IAS) and 95% Cl | 402.1 (138.7, 685.5) | | 361.7 (89.3, 634.0) | | 304.0 (31.8, 576.1) | | 213.5 (-81.7, 508.6) | |
| P-value (difference between<br>groups) | 0.0012** | | 0.0038** | | 0.0250** | | 0.2143** | |
| Change from Baseline in Non-<br>Morphine Pain Medication<br>Usage - Total Daily Dose (mg) | | | | | | | | |
| N | - | - | 33 | 34 | 32 | 34 | 29 | 35 |
| Mean | - | - | 0.0 | 44.9 | -15.6 | 60.9 | -34.5 | 123.9 |
| SD | - | - | 0.0 | 226.3 | 88.4 | 277.7 | 128.9 | 375.4 |
| Median | - | - | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
| Minimum | - | - | 0.0 | 0.0 | -500.0 | 0.0 | -500.0 | -440.0 |
| Maximum | - | - | 0.0 | 1307.5 | 0.0 | 1600.0 | 0.0 | 1600.0 |
| Difference between means<br>(CRFA-IAS) and 95% Cl | - | | -44.9 (-124, 34.0) | | -76.5 (-178, 24.8) | | -158 (-295, -21.7) | |
| P-value (difference between<br>groups) | - | | 0.1668** | | 0.0506** | | 0.0229** | |
| P-value (change from<br>Baseline) | - | | - | 0.2552§ | 0.3251§ | 0.2100§ | 0.1609§ | 0.0591§ |

Table 76. Pain Medication Usage for Subjects Taking Non-Morphine Pain Medication at Any Visit Through 6 Months - TDD

Table disclays total daily dose of normally for the subjects taking nor-morphine pan medication at any follow-up visit. Subjects with only the Baseine visit are excluded.

T-test for two independent means, Wilcoxon rank sum test for two Independent samples, 3paired t-test

Program: HYHOS outout TDD Non-Morphine At Any Visit OM SBS Data Source: hyh03 painmedsub} Date Run: 01MAR2017 - 15:30

An analysis of the primary endpoint for the patients who were opioid dependent at baseline and were evaluated for the primary endpoint demonstrated that there was no relationship between outcome and opioid status as described in Table 82 below. Of the 43 Cooled Radiofrequency Ablation (CRFA) successes, only 10 patients were on opioids at Baseline (23.3%) as compared to 46.7% of the CRFA group who failed the primary endpoint (7/15). Overall, opioid status did not influence the outcomes (p= 0.4073).

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| | Cooled Radiofrequency<br>Ablation (CRFA) | Intraarticular<br>Steroid (IAS) | Overall |
|-----------------------------------------------|------------------------------------------|---------------------------------|-----------------|
| Subjects that are Primary<br>Endpoint success | 10/43 (23.3) | 5/11 (45.5) | 15/54<br>(27.8) |
| Subjects that are Primary<br>Endpoint failure | 7/15 (46.7) | 18/57 (31.6) | 25/72 (34.7) |
| P-value | 0.1073† | 0.4889† | 0.4073†† |

## Table 82: Primary Endpoint Success or Failure for Subjects Taking Opioids at Baseline n/N%

+Fisher exact test for proportions, ++Chi-square test for proportions

The results of the pre-planned statistical analysis of the primary endpoint supports the conclusion that the COOLIEF* Cooled Radiofrequency Probe used for genicular nerve ablation is superior to corticosteroid injection in osteoarthritic subjects for managing knee pain.

# 8. Conclusion

The non-clinical data demonstrate that the COOLIEF* Cooled RF probe devices perform equivalently to the predicate device that is currently marketed. The clinical data demonstrate that the COOLIEF* Cooled RF probe does not present safety or effectiveness issues related to the proposed indication for use. Data collected at the primary endpoint supports the conclusion that the COOLIEF* Cooled Radiofrequency Probe used for genicular nerve ablation is superior to corticosteroid injection in osteoarthritic subjects for managing knee pain. The change to the indications for use does not raise different questions of safety or effectiveness.

End of 510(k) Summary