Medtronic 6470318 Instructions for Use

BRYAN® CERVICAL DISC 0381326E Rev. C

2020-05-11

IMPORTANT INFORMATION ON THE BRYAN® CERVICAL DISC

DESCRIPTION

The BRYAN® Cervical Disc is a cervical disc replacement device comprised of two titanium shells, two titanium retaining wires, a polycarbonate polyurethane nucleus, a polyether polyurethane sheath, and two titanium seal plugs. The articulating surfaces of the device are polyurethane and titanium.

The nucleus is designed to fit between the two shells. The bone-contacting side of each shell includes a sintered titanium porous coating to provide bony ingrowth. The nucleus-contacting side of each shell has a center pin which interacts with a central hole in the nucleus to control the range of motion and help prevent nucleus expulsion. A stop or wing on the anterior aspect of the device, which extends superiorly on the cephalad shell and inferiorly on the caudal shell, is intended to prevent migration of the device into the spinal canal. A polyurethane sheath surrounds the nucleus and is attached to each shell with titanium retaining wires, forming a closed compartment. The device is supplied pre-assembled with the exception of saline and

two seal plugs. Prior to implantation, the surgeon fills the BRYAN function as an initial lubricant for the prosthesis. The surgeon screws titanium alloy seal plugs into one hole in each shell to initially retain the saline.

The prosthesis is held in the intervertebral disc space by the fit of each shell’s outside diameter and convex outer surfaces into a custom-milled cavity created in each vertebral endplate by the surgeon prior to device implantation. The prosthesis was designed to allow for the following motions from the neutral position ex vivo: approximately ±11° flexion/extension, ±11° lateral bending, ±7° rotation, and ±1 mm translation for all cervical disc sizes. The available components are shown in Table 1.

Table 1: BRYAN

Catalog Number Diameter (mm)

6470314 14 6470315 15 6470316 16 6470317 17 6470318 18

Cervical Disc Device Sizes

Cervical Disc with sterile saline. The saline is intended to

After implantation of the device, the resultant interbody height is approximately 6mm. Implied warranties of merchantability and fitness for a particular purpose or use are specifically excluded.

INDICATIONS

The BRYAN® Cervical Disc is indicated in skeletally mature patients for reconstruction of the disc from C3-C7 following singlelevel discectomy for intractable radiculopathy and/or myelopathy. The BRYAN

approach. Intractable radiculopathy and/or myelopathy is defined as any combination of the following: disc herniation with radiculopathy, spondylotic radiculopathy, disc herniation with myelopathy, or spondylotic myelopathy resulting in impaired function and at least one clinical neurological sign associated with the cervical level to be treated, and necessitating surgery as demonstrated using computed tomography (CT), myelography and CT, and/or magnetic resonance imaging (MRI). Patients

receiving the BRYAN BRYAN

Cervical Disc.

Cervical Disc should have failed at least six weeks of non-operative treatment prior to implantation of the

device is implanted via an open anterior

CONTRAINDICATIONS

The BRYAN® Cervical Disc should not be implanted in patients with the following conditions:

▪ Active systemic infection or infection at the operating site. ▪ Allergy to titanium, polyurethane, or ethylene oxide residues. ▪ Osteoporosis defined as a DEXA bone mineral density T-score equal to or worse than -2.5. ▪ Moderate to advanced spondylosis characterized by bridging osteophytes, marked reduction or absence of motion, or

collapse of the intervertebral disc space of greater than 50% of its normal height.

▪ Marked cervical instability on radiographs (e.g., radiographic signs of subluxation greater than 3.5mm or angulation of the

disc space more than 11° greater than adjacent segments).

▪ Significant cervical anatomical deformity or compromised vertebral bodies at the index level (e.g., ankylosing spondylitis,

rheumatoid arthritis, or compromise due to current or past trauma).

▪ Significant kyphotic deformity or significant reversal of lordosis. ▪ Symptoms necessitating surgical treatment at more than one cervical level.

WARNINGS

Correct sizing and placement of the device is essential to optimal performance. The BRYAN® Cervical Disc should only be used by surgeons experienced in the surgical procedure and have undergone adequate hands-on training with this specific device. Medtronic will offer hand-on training to physicians prior to the first surgical treatment. A lack of adequate experience and/or training may lead to a higher incidence of adverse events, such as neurological complications.

Due to the proximity of vascular and neurological structures to the implantation site, there are risks of serious or fatal hemorrhage and risks of neurological damage with the use of this device. Serious or fatal hemorrhage may also occur if the major cervical blood vessels are eroded or punctured during implantation and are subsequently damaged due to breakage of implants, migration of implants, or if pulsatile erosion of the vessels occurs because of close apposition of the implants.

PRECAUTIONS

The safety and effectiveness of this device has not been established in patients with the following conditions:

▪ Axial neck pain as solitary symptom. ▪ Not skeletally mature. ▪ Prior cervical spine surgery, including prior surgery at the index level. ▪ Facet joint pathology of involved vertebral bodies. ▪ Active malignancy. ▪ Paget’s disease, osteomalacia, or other metabolic bone disease. ▪ Chronic or acute renal failure or history of renal disease. ▪ Taking medications known to potentially interfere with bone/soft tissue healing (e.g., steroids). ▪ Pregnant. ▪ Unstable cardiac disease. ▪ Diabetes mellitus requiring daily insulin management. ▪ Extreme obesity as defined by the NIH Clinical Guidelines Body Mass Index (i.e., BMI ≥40).

There were no patients in the pivotal study who were less than 21 years of age. The safety and effectiveness of this device has not been studied in the pediatric or adolescent age group (<21 years old).

The safety and effectiveness of this device has not been established in patients who were not refractory to at least six weeks of unsuccessful conservative treatment or had signs of progression or spinal cord/nerve root compression with continued nonoperative care.

Implanted metal alloys release metallic ions into the body. The long term effect of these ions on the body is not known. In order to minimize the risk of periprosthetic vertebral fractures, surgeons must consider all comorbidities, past and present,

medications, previous treatments, etc. Surgeons should screen patients to determine if a DEXA bone mineral density measurement is necessary. If DEXA is performed, the patient should not receive the BRYAN® Cervical Disc (per the Contraindications) if the DEXA bone mineral density T-score is ≤ -2.5, as the patient may be osteoporotic. It may also be advisable to exclude patients with a T score ≤ -1.0, as those patients may be osteopenic.

Patients in the clinical study were instructed to use non-steroidal anti-inflammatory drugs (NSAIDs) for two weeks postoperatively. Dosing and frequency were left to the discretion of the physician. It has been reported in the literature that short-term postoperative use of NSAIDs may reduce the instance of heterotopic ossification.

Correct selection of the appropriate implant size is extremely important to ensure the placement and function of the disc. Patient selection is extremely important. In selecting patients for a total disc replacement, the following factors can be of

extreme importance to the success of the procedure: the patient’s occupation or activity level; a condition of senility, mental illness, alcoholism or drug abuse; certain degenerative diseases (e.g., degenerative scoliosis or ankylosing spondylitis) that may be so advanced at the time of implantation that the expected useful life of the device is substantially decreased, and medical conditions that may affect postoperative management, such as Alzheimer’s disease and emphysema.

Surgical implants must never be re-used or re-implanted. Even though the device appears undamaged, it may have small defects and internal stress patterns that may lead to early breakage.

This system was designed for single patient use only. Do not reuse, reprocess, or resterilize this product. Reuse, reprocessing, or resterilization may compromise the structural integrity of the device and/or create a risk of contamination of the device, which could result in patient injury, illness, or death.

Use aseptic technique when removing the BRYAN Use care when handling a BRYAN

implant. Damaged implants are no longer functionally reliable. BRYAN

manufacturers. Patients should be instructed in postoperative care procedures and should be advised of the importance of adhering to these

procedures for successful treatment with the device. Patients should be advised to avoid any activities that require repeated

Cervical Disc components should not be used with components or instruments of spinal systems from other

disc component to ensure it does not come in contact with objects that could damage the

Cervical Disc device from the innermost packaging.

bending, lifting, and twisting, such as athletic activities. Gradual increase in physical activity will depend on individual patient progress.

PHYSICIAN NOTE: Although the physician is the learned intermediary between the company and the patient, the important medical information given in this document should be conveyed to the patient.

FOR US AUDIENCES ONLY

CAUTION: FEDERAL LAW (USA) RESTRICTS THESE DEVICES TO SALE BY OR ON THE ORDER OF A PHYSICIAN.

MRI Information for the BRYAN® Cervical Disc Implant

MR Conditional

Non-clinical testing demonstrated that the BRYAN following conditions:

Cervical Disc is MR Conditional. It can be scanned safely under the

▪ Static magnetic field of 1.5 Tesla and 3.0 Tesla ▪ Highest spatial gradient magnetic field of 720 Gauss/cm ▪ Maximum whole body average specific absorption rate (SAR) of 2.0 W/kg or less under Normal Operating Mode only, for 15

minutes of scanning (per pulse sequence).

In non-clinical testing, the BRYAN averaged SAR of 2.1 W/kg, as assessed by calorimetry for 15 minutes of MR scanning (per pulse sequence) in a 1.5 Tesla MR system (1.5 Tesla/64 MHz, Magnetom, Siemens Medical Solutions, Malvern, PA. Software Numaris/4,Version Syngo MR 2002B

DHHS). Additionally, the BRYAN body averaged SAR of 2.7 W/kg, as assessed by calorimetry for 15 minutes of MR scanning (per pulse sequence) in a 3 Tesla MR system (3 Tesla/128 MHz, Excite, G3.0-052B, General Electric Healthcare, Milwaukee, WI).

Cervical Disc produced a maximum temperature rise of 1.7º C at a maximum whole body

Cervical Disc System produced a maximum temperature rise of 2.0ºC at a maximum whole

Artifact Information

MR image quality may be compromised if the area of interest is in the same area or relatively close to the position of the BRYAN

Cervical Disc. The artifact size information is as follows:

Pulse Sequence T1-SE T1-SE GRE GRE Signal Void Size

Imaging Plane Parallel Perpendicular Parallel Perpendicular

The image artifact extends approximately 25 mm from the device when scanned in non-clinical testing using a gradient echo sequence in a 3 Tesla MR system (Excite, HDx, Software 14X.M5, General Electric Healthcare, Milwaukee, WI) using a transmit/receive RF body coil.

582 mm

557 mm

1,350 mm

1,287 mm

MRI Patient Counseling Information

Physicians should communicate with the patient the following information about MR with respect to the BRYAN® Cervical Disc:

▪ BRYAN

Cervical Disc performance has been established for MRI systems at field strengths of 1.5 and 3.0 Tesla.

▪ During an MRI, the patient may notice a warming sensation around the implant or feel a tingling sensation. If the warming or

tingling sensation is uncomfortable, the patient should communicate this to the MR technologist, the MRI should be stopped, and the settings adjusted to reduce or eliminate the sensation. The highest temperature change observed in nonclinical testing was +2.0ºC (associated with specific conditions listed).

▪ Additionally, the metal in the implant may cause the MRI image to be distorted in the area around the implant. The MRI can

be adjusted to minimize the image distortion.

Physicians should instruct patients to:

▪ Inform any healthcare personnel (e.g., doctor or MR technologist) that they have an implanted cervical disc prior to

receiving an MRI.

▪ The patient’s doctor will recommend whether or not an MRI is appropriate.

POTENTIAL ADVERSE EVENTS

Risks associated with the use of the BRYAN® Cervical Disc include those commonly associated with any surgery, those specifically associated with cervical spinal surgery using an anterior approach, and those associated with a spinal implant, as

well as those pertaining to the BRYAN categories. There is also the risk that this surgical procedure will not be effective, and may not relieve or may cause worsening of preoperative symptoms. Some of these effects were observed in the clinical study and therefore have been previously reported in the adverse events tables.

1. Risks associated with any surgical procedure are those such as abscess; cellulitis; wound dehiscence; wound necrosis;

edema; hematoma; heart and vascular complications; hypertension; thrombosis; ischemia; embolism; thromboembolism; hemorrhage; thrombophlebitis; adverse reactions to anesthesia; pulmonary complications; gastrointestinal complications; organ, nerve or muscular damage; seizure, convulsion, or changes to mental status; and complications of pregnancy including miscarriage and fetal birth defects.

2. Risks associated with anterior interbody surgery of the cervical spine include dysphagia; dysphasia; dysphonia; hoarseness;

vocal cord paralysis; laryngeal palsy; sore throat; recurring aspirations; nerve deficits or damage; tracheal, esophageal, and

Cervical Disc. However, the causality of these adverse events is not exclusive to these

pharyngeal perforation; airway obstruction; external chylorrhea; warmth or tingling in the extremities; deficit or damage to the spinal cord, nerve roots, or nerves possibly resulting in paralysis or pain; dural tears or leaking; cerebrospinal fistula; discitis, arachnoiditis, and/or other types of inflammation; loss of disc height; loss of proper curvature, correction, height or reduction of the spine; vertebral slipping; scarring, herniation or degeneration of adjacent discs; surrounding soft tissue damage, spinal stenosis; spondylolysis; otitis media; fistula; vascular damage and/or rupture; and headache.

Risks associated with implants in the spine, including the BRYAN

device, are early or late loosening of the components; disassembly; bending or breakage of any or all of the components; implant migration; malpositioning of implant; loss of purchase; sizing issues with components; anatomical or technical difficulties; implant fracture; bone fracture; skin penetration, irritation, pain, bursitis resulting from pressure on the skin from component parts in patients with inadequate tissue coverage over the implant; foreign body reaction to the implants including possible tumor formation, autoimmune disease, metallosis, and/or scarring; possible tissue reaction; bone resorption; bone formation that may reduce spinal motion or result in a fusion, either at the treated level or at adjacent levels; development of new radiculopathy; myelopathy or pain; tissue or nerve damage caused by improper positioning and placement of implants or instruments; loss of neurological function; decreased strength of extremities; decreased reflexes; appearance of cord or nerve root injury; loss of bowel and/or bladder control; and interference with radiographic imaging because of the presence of the implant.

4. Wound, local, and/or systemic infections.

5. Surgical instrument bending or breakage, as well as the possibility of a fragment of a broken instrument remaining in the

patient.

6. Inability to resume activities of normal daily living, including loss of consortium.

7. Death.

NOTE: Additional surgery may be necessary to correct some of the adverse effects.

CLINICAL STUDIES

A multi-center, prospective, randomized, non-inferiority clinical trial of the BRYAN® Cervical Disc was conducted in the US comparing the anterior spinal use of the BRYAN

plating stabilization, the control, for reconstruction of the disc from C3-C7 following single-level discectomy for intractable radiculopathy and/or myelopathy.

The IDE study was approved for a total of 470 patients. Medtronic performed a pre-specified interim statistical analysis when approximately 300 implanted subjects had completed their 24-month follow-up visit. As predetermined at the time of the IDE

study initiation, if the results of this interim analysis demonstrated non-inferiority of the subjects receiving the BRYAN compared to controls, the sponsor would submit a marketing application.

A total of 463 patients were treated at 30 investigational centers in the clinical trial: 242 patients in the investigational BRYAN device treatment group and 221 patients in the control group. A post-approval study required as a condition of PMA approval was conducted to follow the original IDE subject cohort through 120 months postoperatively. Additionally, an enhanced surveillance study was also conducted collect adverse event and complaint information for five (5) years after device approval.

device to anterior cervical discectomy and fusion (ACDF) using allograft and

device

SUMMARY OF THE IDE AND POST-APPROVAL STUDY (PAS) METHODS

Study Objectives

IDE Study

The primary objective of the IDE study was to demonstrate that the overall success rate for the investigational BRYAN® Cervical Disc treatment is statistically non-inferior to the overall success rate of the control treatment at 24 months following surgery. If statistical non-inferiority was established, the investigational treatment is considered to be safe and effective, and the study was considered a success.

Other secondary objectives were to compare the success rates of individual effectiveness endpoints and neurological status at 24 months following surgery.

Post-approval Study

The primary objective of the post-approval study was to demonstrate that the overall success rate for the investigational BRYAN

following surgery. If statistical non-inferiority was established, the investigational treatment is considered to be safe and effective, and the study was considered a success.

Other secondary objectives were to compare the success rates of individual effectiveness endpoints and neurological status at 120 months following surgery.

Cervical Disc treatment is statistically non-inferior to the overall success rate of the control treatment at 120 months

Enhanced Surveillance Study

The study objective was to collect the information for any adverse event and complaint, including those not associated with any adverse clinical effect, received by the company for the BRYAN

Cervical Disc device following 5 years after device approval.

Study Designs

IDE Study

The IDE study was a multi-center, prospective, randomized, controlled clinical trial comparing the BRYAN® Cervical Disc treatment to the control treatment. Data were collected at pre-operative, discharge, 6 weeks, 3 months, 6 months, 12 months (1 year), and at 24 months (2 years). Additionally, 36 month data (3 years) was also collected prior to the start of the post-approval study.

Post-approval Study

The post-approval study was a prospective study to continue follow-up on the subjects who participated in the IDE study. Data were collected at 48 months (4 years), 60 months (5 years), 84 months (7 years), and at 120 months (10 years).

Enhanced Surveillance Study

Enhanced Surveillance data was collected annually on the post-market device for five (5) years after PMA approval.

Inclusion and Exclusion Criteria

To qualify for enrollment in the IDE study, subjects met all of the following inclusion criteria and none of the following exclusion criteria.

Inclusion Criteria

▪ Requires surgical treatment at any one level (C3-4, C4-5, C5-6, or C6-7) that failed conservative treatment (by the

investigator or referring physician) lasting at least six weeks; for any combination of the following: disc herniation with radiculopathy, spondylotic radiculopathy, disc herniation with myelopathy, or spondylotic myelopathy. The six-week conservative treatment period may be waived in cases of myelopathy requiring immediate treatment (e.g., acute onset of clinically significant signs).

▪ The requirement for surgical treatment must be demonstrated using computed tomography (CT), or myelography and CT,

and/or magnetic resonance imaging (MRI).

▪ Patient must score 30 or more points on the NDI questionnaire and exhibit at least one clinical sign associated with the

cervical level to be treated (i.e., abnormal reflex, decreased motor strength, or abnormal dermatome sensitivity).

▪ Skeletally mature (at least 21 years old). ▪ Willing and likely to follow the requirements of the protocol. ▪ Voluntarily signs the Patient Informed Consent.

Exclusion Criteria

A patient meeting any of the following criteria was to be excluded from the study:

▪ Active systemic infection or infection at the operating site. ▪ Metabolic bone disease, such as osteoporosis, which is defined as a bone mineral density T-score equal to or worse than –

2.5.

Note: If the investigator detects the presence of significant radiolucence, bone mineral density (BMD) scan in the spine, wrist, and femoral neck must be obtained to verify the absence of osteoporosis.

▪ Known allergy to titanium, polyurethane, or ethylene oxide residuals. ▪ Concomitant conditions requiring steroid treatment. ▪ Diabetes mellitus requiring daily insulin management. ▪ Extreme obesity, as defined by NIH Clinical Guidelines Body Mass Index. ▪ Pregnancy. ▪ Axial neck pain as the solitary symptom. ▪ Previous cervical spine surgery. ▪ A medical condition that may interfere with the postoperative management program, such as advanced emphysema, or

Alzheimer’s disease.

▪ A medical condition that may result in patient death prior to study completion.

▪ Unstable cardiac disease.

▪ Active malignancy. ▪ Current or recent history of substance abuse (alcoholism and/or narcotic addiction) requiring intervention. ▪ Signs of being geographically unstable, such as recent or pending divorce, or high level of job dissatisfaction.

Patients with the following radiographic features at the symptomatic level were excluded from the study. These features at adjacent levels did not disqualify the patient from the study.

▪ Significant cervical anatomical deformity (e.g., ankylosing spondylitis, rheumatoid arthritis, etc.). ▪ Moderate to advanced spondylosis. Patients who demonstrate advanced degenerative changes. Such advanced changes

are characterized by any one or combination of the following:

▪ Bridging osteophytes.

▪ Marked reduction or absence of motion.

▪ Collapse of the intervertebral disc space of greater than 50% of its normal height. ▪ Radiographic signs of subluxation greater than 3.5mm. ▪ Angulation of the disc space more than 11° greater than adjacent segments.

▪ Significant kyphotic deformity or significant reversal of lordosis.

Study Population

IDE and Post-Approval Studies

The studies included 463 enrolled subjects who were at least 21 years old at the time of the surgery and met the study inclusion and exclusion criteria.

Enhanced Surveillance Study

The study population was as per device indication. This device is indicated in skeletally mature patients for reconstruction of the disc from C3-C7 following single-level discectomy for intractable radiculopathy and/or myelopathy.

Post-Operative Care

The recommended post-operative care included avoidance of heavy physical activity and limitations on extended automobile rides, working, lifting, bending and twisting. The recommended post-operative regimen also included avoidance of physically demanding sports or recreational activities for 3 months post-operatively. The decision whether to use a post-operative orthosis was left to the discretion of the investigator. Investigational patients were instructed to use NSAIDs for the first two weeks postoperatively.

IDE and PAS Follow-up Schedules

For the IDE study, patients were evaluated preoperatively (within 2 months of surgery), intraoperatively, and post-operatively at 6 weeks, 3 months, 6 months, 12 months (1 year), and at 24 months (2 years). Additionally, patients were also evaluated at 36 months (3 years) prior to the beginning of the post-approval study. For the post-approval study, patients were evaluated at 48 months, 60 months, 84 months, and 120 months. Complications and adverse events, device-related or not, were evaluated over the course of the clinical trial. At each evaluation timepoint, the primary and secondary clinical and radiographic outcome parameters were evaluated. For the IDE, success was determined from data collected during the initial 24 months of follow-up. For the post-approval study, success was determined from the data collected up to 120 months.

Data Source

New data collection

Study Endpoints

IDE and PAS Study Endpoints

The primary endpoint was determined at 24 months (for the IDE) and 120 months (for the PAS) as a composite variable termed overall success which included key safety and efficacy considerations. The efficacy variable was Neck Disability Index (NDI) success, which was defined as at least 15-points improvement in the postoperative NDI score compared to the pre-operative score. Safety variables included:

▪ Maintenance or improvement in neurological status from preoperative ▪ No serious adverse events classified as implant associated or implant/surgical procedure associated, and ▪ No additional surgical procedure classified as a “failure.”

Secondary endpoints for both the IDE and post-approval studies included neck pain, arm pain, general heatlh status, patient satisfaction, patient global perceived effect, and gait assessments.

Enhanced Surveillance Study Endpoint

Complaints and adverse events for up to five (5) years after BRYAN® Cervical Disc device approval.

Strengths and Limitations of the Clinical Study Design

The following are important study design strengths of the IDE, post-approval, and enhanced surveillance studies:

▪ The PAS provided extended term profile of safety and effectiveness as well as functional data established on a multicenter,

randomized, controlled clincal trial.

▪ The consistency of data gathering approaches and endpoints was maintained through both the IDE and post-approval

studies.

▪ The strength and reliability of the final IDE and PAS conclusions were confirmed by several sensitivity analyses. ▪ The study design minimized potential biases by integrating a wide variety of assessments including subjective data,

physician-judged and core laboratory-assessed evaluations.

▪ The duration of the enhanced surveillance study was five (5) years after PMA approval which allowed time to monitor longer

term adverse events and complaints received by the sponsor for the device in the post-marketing setting.

The following potential study design limitations should also be considered when interpreting the results of the IDE, postapproval, and enhanced surveillance studies:

▪ Though there were no significant differences in Adverse Event (AE) rates between the groups, categorization of AE is

suboptimal in that all systemic AEs were considered non-device or non-procedure related, which may or may not be the case. AE rates should be interpreted accordingly.

▪ Data on neurologic outcomes is incomplete in that relatedness to the device and procedure could not be determined and

should be interpreted accordingly.

▪ There were a total of 37 reported cases of dysphagia or dysphonia in the investigational group. Of those reported cases, 10

were deemed unrelated to the device or surgical procedure. Of those 10 cases, eight were deemed unrelated to the BRYAN

cases were undetermined but could potentially be related to the surgical procedure.

device or procedure, although definitive lack of device or procedure-relatedness cannot be determined. Two other

▪ Avoidance of adjacent level degeneration (device vs ACDF control) could not be demonstrated. There was also a lack of

significance shown for surrogate measures.

▪ Fusion outcomes on those subjects requiring a secondary surgical intervention (SSI) for BRYAN

captured during the study. As such, fusion outcomes after SSI are not known (e.g., the possibility of an incomplete fusion or delayed fusion is not known.

device removal was not

▪ There may have been under-reporting of adverse events and complaints to the company during the enhanced surveillance

study due to the spontaneous nature of the post-market reporting. Therefore, the true number of the post-market adverse events and complaints duing the 5-year study period may not be known.

SUMMARY OF THE IDE AND POST-APPROVAL STUDY RESULTS

Subject Demographics and Baseline Paremeters

Table 2 summarizes the study patient demographics and baseline characteristics.

Table 2: Study Patient Demographics and Baseline Characteristics

Variables Investigational

(N=242)

Age (years) 44.4 ± 7.9 44.7 ± 8.6 0.723

Height (inches) 67.6 ± 3.8 67.6 ± 3.8 0.991

Weight (lbs.) 173.3 ± 37.7 180.0 ± 38.9 0.061

BMI 26.6 ± 4.8 27.6 ± 5.0 0.027

Sex (% male) 45.5% 51.1% 0.228

Race

Caucasian

Black Asian

Hispanic

Other

Marital Status

Single

Married

Divorced

Separated

Widowed

Education Level

< High School

High School

> High School

Worker’s Compensation 6.2% 5.0% 0.687

Unresolved Spinal Litigation 2.5% 2.7% 1.000

Current Tobacco Use 25.5% 24.0% 0.746

Current Alcohol Use 8.4% 4.1% 0.083

Preoperative Work Status 64.5% 65.0% 0.923

Preoperative NDI Score 51.4 ± 15.3 50.2 ± 15.9 0.392

Duration of Symptoms

< 6 wks.

6 wks. – 3 mos.

3 – 6 mos

6 mos – 1 yr.

1 – 2 yrs.

> 2 yrs.

231

3 1 3 4

184

6 4

16 63

161

10 36 47 52 38 59

Control (N=221)

204

5 2 7 3

169

1 2

15 65

141

13 52 39 37 28 52

p-value

0.527

0.437

0.743

0.180

In addition to the study patients described in Table 2, 117 patients were randomized but declined participation in the study prior to receiving the assigned treatment. Of these patients, 37 would have received the BRYAN

potential control patients. The demographic and preoperative characteristics of the patients who declined to participate were comparable to the study patients.

There were 12 patients in this study who were randomized to the investigational treatment but received the control treatment, and one patient who was randomized to the control treatment but received the investigational treatment. Most of these were

disc treatment, while 80 were

intraoperative conversions due to sizing issues or difficulty visualizing the target disc space. Table 3 summarizes the surgical and hospitalization information.

Table 3: Surgical Results

Investigational Control Probability that the surgical measurements of the

investigational group are less than that of the control

group

(%)

Mean operative time (hrs) 2.2 (n=241) 1.4 (n=221) 0.0

Mean EBL (ml) 91.5 (n=240) 59.6 (n=221) 0.0

Hospitalization (days) 1.1 (n=242) 1.0 (n=221) 4.7

Spinal level treated

(%) 3 (1.2) 0 (0.0) N/A

3-4

(%) 12 (5.0) 17 (7.7) N/A

4-5

(%) 140 (57.9) 110 (49.8) N/A

5-6

(%) 87 (36.0) 94 (42.5) N/A

6-7

BRYAN

Cervical Disc Size Used

14mm (%) 55 (22.7) N/A N/A 15mm (%) 66 (27.3) N/A N/A 16mm (%) 57 (23.6) N/A N/A 17mm (%) 36 (14.8) N/A N/A 18mm (%) 28 (11.6) N/A N/A

Safety Results

The safety of the BRYAN® Cervical Disc was assessed by monitoring intraoperative and postoperative complications. Radiographs were examined for device subsidence, functional spinal unit height maintenance, device migration, and breakage. All radiographic endpoints were evaluated independently by a core laboratory and reviewed by independent radiographic reviewers. In addition, some radiographic observations, such as implant malposition, reported by investigators were handled as adverse events.

Adverse Events

The adverse effects, as shown in Table 4, were reported from the 242 BRYAN® disc patients and 221 control patients enrolled in the multi-center clinical study. Adverse event rates presented are based on the number of patients having at least one occurrence for a particular adverse event divided by the total number of patients in that treatment group. Patients experiencing adverse events in more than one category are represented in each category in which they experienced an adverse event. As shown in Table 5, a minority of the adverse events were deemed related to the study treatment. Relationship determinations were approved by a physician reviewer.

Table 4: Adverse Events for US IDE

Complication Surgery Postoperative 6 Weeks 3 Months 6 Months 12 Months 24 Months # of Patients Reporting &

Inves.

Anatomical/Technical Difficulty

Cancer 00 0 0 1000101011 4 (1.7)41 (0.5)

Cardiovascular 10 1 0 0110103037 8 (3.3)107 (3.2)

Carpal Tunnel Syndrome

Death 00 0 0 0000000100 0 (0.0)01 (0.5)

Dysphagia/ Dysphonia 15 5 13 12 2 1 0 3 0 0 0 0 2 2 29 (12)

Gastrointestinal 02 2 1 0210312295 12 (5.0)1711 (5.0)

Implant Displacement/ Loosening

Infection 0 0 8 3 4010512246 22 (9.1)2412 (5.4)

Malpositioned Implant 1 0 0 0 0 0 0 0 1 0 0 0 0 0 2 (0.8)

01 0 0 0000000000 0 (0.0)01 (0.5)

00 0 1 2053114111 12 (5.0)137 (3.2)

00 0 0 0000000000 0 (0.0)00 (0.0)

Control

Inves.

and Post-Approval Studies

Control

Inves.

Control

Inves.

Control

Inves.

Control

Inves.

Control

Inves.

Control

Total adverse events

Investig. #

Patients (% of

242) Total # Events

Control # Patients

(% of 221) Total #

Events

20 (9.0)

0 (0.0)

Table 4: Adverse Events for US IDE1 and Post-Approval Studies (continued)

Complication Surgery Postoperative 6 Weeks 3 Months 6 Months 12 Months 24 Months # of Patients Reporting &

Inves.

Control

Inves.

Control

Inves.

Control

Inves.

Control

Inves.

Control

Inves.

Control

Total adverse events

Investig. #

Patients (% of

242) Total # Events

Control # Patients

(% of 221) Total #

Events

Neck and/or Arm Pain 1 3 25 15 25 18 24 26 22 19 34 22 11 19 110 (45.5)

Neurological 1 1 6 5 3 7 17 11 10 10 21 11 11 10 55 (22.7)

142

Non-Union 00 0 0 0102010102 0 (0.0)07 (3.2)

Non-Union – Outcome Pending

Other

Other Pain

00 0 0 0102000100 0 (0.0)04 (1.8)

11 7 19 5 9 5 10 8 13 9 26 12 31 21 79 (32.6)

0 1 7 5 6 4 10 12 9 7 16 9 17 13 54 (22.3)

119

Respiratory 2 0 1 4 1002003330 10 (4.1)109 (4.1)

Spinal Event

Cervical Adjacent Non Contiguous

Cervical Adjacent Contiguous

Cervical Target Level 1 1 0 0 0 0 4 0 0 1 5 1 4 1 13 (5.4)

Non-Cervical Level 0 0 1 0 3 2 4 1 1 2 5 8 5 7 18 (7.4)

1 1 1 3 4 4 12 4 3 7 15 13 15 22 44 (18.2)

00 0 1 0020000112 3 (1.2)34 (1.8)

00 0 2 12232453512 15 (6.2)1526 (11.8)

Subsidence 00 0 0 0001000000 0 (0.0)01 (0.5)

Trauma 1 0 2 3 2 1 5 5 12 4 15 8 14 9 40 (16.5)

Urogenital 0 0 0 0 0 0 0 1 2 0 5 4 6 2 10 (4.1)

Vascular Injury IntraOp

21 0 2 0000000000 2 (0.8)23 (1.4)

Any Adverse Event 208 (86.0)

624

90 (40.7)

122

48 (21.7)

51 (23.1)

45 (20.4)

44 (19.9)

3 (1.4)

19 (8.6)

23 (10.4)

7 (3.2)

185 (83.7)

476

Complication 36 Months 48 Months 60 Months 72 Months 84 Months 96 Months 108 Months 120 Months # of Patients Reporting &

Anatomical/Technical Difficulty

Inves.

0000000000 000000 0 (0.0)

Control

Inves.

Control

Inves.

Control

Inves.

Control

Inves.

Control

Inves.

Control

Inves.

Control

Inves.

Control

Cancer 1201112011 110010 9 (3.7)

Cardiovascular 65106446066 274312 40 (16.5)4931 (14.0)

Carpal Tunnel Syndrome

1023000002 300000 17 (7.0)1910 (4.5)

Death 0001002000 000100 2 (0.8)

Dysphagia/Dysphonia 0 0 1 0 1 1 0 0 2 1 0 1 0 0 1 0 32 (13.2)

Gastrointestinal 9 11 13 6 7 7 13 5 6 5 4 4 3 1 0 2 49 (20.2)

Implant Displacement/ Loosening

0010100000 000000 2 (0.8)

Infection 38811778463345700 43 (17.8)6540 (18.1)

Malpositioned Implant 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 2 (0.8)

Neck and/or Arm Pain 17 8 17 19 6 6 7 5 9 4 0 4 8 3 0 4 136 (56.2)

Neurological 6 5 14 6 14 12 3 10 11 6 4 3 7 3 0 0 88 (36.4)

Non-Union 0000001000 000000 1 (0.4)

Non-Union – Outcome Pending

Other

0000000000 000000 0 (0.0)

41 24 54 26 30 21 18 11 21 19 11 8 12 4 5 7 127 (52.5)

Total adverse events

Investig. # Patients

(% of 242) Total #

(≤120 Months)

Events

206

128

311

Control # Patients

(% of 221) Total #

Events

1 (0.5)

7 (3.2)

3 (1.4)

23 (10.4)

34 (15.4)

0 (0.0)

112 (50.7)

175

74 (33.5)

100

7 (3.2)

4 (1.8)

90 (40.7)

187

Complication 36 Months 48 Months 60 Months 72 Months 84 Months 96 Months 108 Months 120 Months # of Patients Reporting &

Inves.

Control

Inves.

Control

Inves.

Control

Inves.

Control

Inves.

Control

Inves.

Control

Inves.

Control

Total adverse events

Investig. # Patients

(% of 242) Total #

(≤120 Months)

Events

Control # Patients

(% of 221) Total #

Events

Other Pain

Respiratory 4153432111 212201 24 (9.9)3021 (9.5)

Spinal Event

Cervical Adjacent Non Contiguous

Cervical Adjacent Contiguous

Cervical Target Level 2 2 7 2 4 4 1 1 6 0 1 0 0 0 3 0 33 (13.6)

Non-Cervical Level 2 1 8 9 5 2 5 3 4 3 4 3 0 4 0 0 40 (16.5)

Subsidence 0000000000 000000 0 (0.0)

Trauma 14 10 21 9 14 8 7 5 13 4 5 2 5 4 0 0 78 (32.2)

Urogenital 42912446452451300 36 (14.9)4629 (13.1)

Vascular Injury Intra-Op0000000000 000000 2 (0.8)

Any Adverse Event 231 (95.5)

21 14 17 27 18 23 10 8 8 13 1 7 2 9 8 4 97 (40.1)

9 8 24 18 16 14 9 8 13 9 7 6 4 8 4 2 95 (39.3)

1202001001 000100 6 (2.5)

4395782435 234402 41 (16.9)4651 (21.3)

150

137

130

1400

99 (44.8)

156

82 (37.1)

127

9 (4.1)

12 (5.4)

37 (16.7)

1 (0.5)

46 (20.8)

3 (1.4)

199 (90.0)

1093

_________________________________________________________

Some adverse events may lead to additional surgeries or interventions. Refer to Table 7 for more information.

Control=Single-level anterior interbody fusion procedure with allograft and plate stabilization.

Other consists of various events that do not fit into another category, such as rash, depression, or hypertension. This category also consists of three events related to an investigator’s report of lack of motion of the prosthesis. A formal evaluation of heterotopic ossification was not included in the IDE protocol.

Other Pain consists of non-neck and/or arm pain events such as headache, lower back pain, or leg pain.

Spinal event consists of events reported as a spinal diagnosis/disorder (e.g., degenerative disc disease, disc herniation, stenosis, scoliosis).

Table 5: Adverse Events Classified as Device-Related or Device/Surgical Procedure-Related in US IDE

and Post-

Approval Studies

Complication Surgery Postoperative 6 Weeks 3 Months 6 Months 12 Months 24 Months # of Patients Reporting &

Inves.

Control

Inves.

Control

Inves.

Control

Inves.

Control

Inves.

Control

Inves.

Control

Inves.

Control

Total adverse events

Invest. #

Patients (% of

242) Total # Events

Control #

Patients (% of

221) Total # Events

Implant Displacement/ Loosening

Malpositioned Implant

Neck and/or Arm Pain

Non-Union 0 0 0 0 0102000102 0 (0.0)06 (2.7)

Non-Union – Outcome Pending

Other

Spinal Event 00 0 0 0020013021 6 (2.5)72 (0.9)

Cervical Adjacent Contiguous

Cervical Target Level

Subsidence 00 0 0 0001000000 0 (0.0)01 (0.5)

Trauma 00 0 0 0000100000 1 (0.4)10 (0.0)

Any Adverse Event 13 (5.4)

00 0 0 0000000000 0 (0.0)00 (0.0)

10 0 0 0000100000 1 (0.4)10 (0.0)

00 2 0 0100000000 2 (0.8)21 (0.5)

00 0 0 0102000100 0 (0.0)04 (1.8)

00 0 0 0000101010 3 (1.2)30 (0.0)

00 0 0 0000010000 0 (0.0)01 (0.5)

00 0 0 0020003021 6 (2.5)71 (0.5)

14 (6.3)

Complication 36 Months 48 Months 60 Months 72 Months 84 Months 96 Months 108 Months 120 Months # of Patients Reporting &

Total adverse events

Invest. # Patients (% of 242) Total #

Events

Control # Patients

(% of 221) Total #

Events

Invest.

Implant Displacement/ Loosening

Malpositioned Implant

Neck and/or Arm Pain

Non-Union 0000000000000000 0 (0.0)06 (2.7)

Non-Union – Outcome Pending

Other 0000000000000000 3 (1.2)30 (0.0)

Spinal Event 0011102030000020 15 (6.2)163 (1.4)

Cervical Adjacent Contiguous

Cervical Target Level

Subsidence 0000000000000000 0 (0.0)01 (0.5)

Trauma 0000000000000000 1 (0.4)10 (0.0)

Any Adverse Event 24 (9.9)

0010100000000000 2 (0.8)20 (0.0)

0000000000000000 1 (0.4)10 (0.0)

0000000010000000 3 (1.2)31 (0.5)

0000000000000000 0 (0.0)04 (1.8)

0001001000000000 1 (1.4)12 (0.9)

0010101030000020 14 (5.8)151 (0.5)

Control

Invest.

Control

Invest.

Control

Invest.

Control

Invest.

Control

Invest.

Control

Invest.

Control

15 (6.8)

* denotes WHO Grade 3 or 4 serious adverse events. Two deaths were reported in the investigational group. One reported investigational death was due to end stage COPD

approximately 75 months postoperatively, and the other was reported as secondary to prescription drug medication approximately 78 months postoperatively. Neither of the deaths were considered to be associated with the investigational implant or implantation procedure.

Three deaths were reported in the control group. One reported control death was due to injuries sustained in a motor vehicle crash approximately 17 months postoperatively. The second death was due to a drug overdose approximately 54 months postoperatively. The third death was reported as exacerbation of cardiovascular and ischemic heart disease approximately 108 months postoperatively. None of these deaths were considered to be associated with the control group implant or implantation procedure.

The total number of spinal events (overall and those classified as device-related or device/surgical procedure-related) were numerically greater in the investigational group than the control group. Although not statistically significant, the findings are clinically significant.

An time to event anlaysis was conducted on adverse events up to 120 months. The results are presented in Table 6.

Table 6: Time to Event Analysis of Adverse Events in Main Categories Up to 120 Month Interval

INV (N=242) CTR (N=221) P-Value

(Log-Rank Test)

Total Subjects Experiencing

Events Subjects (n) (cumulative

rate %)

Events Subjects (n) (cumulative

rate %)

1400 231 (98.4%) 1093 199 (98.8%) 0.166

Adverse Events Anatomical/Technical Difficulty 0 0 (0.0%) 1 1 (0.5%) 0.295 Cancer 11 9 (8.1%) 7 7 (4.8%) 0.860 Cardiovascular 49 40 (27.6%) 41 31 (26.1%) 0.653 Carpal Tunnel Syndrome 19 17 (8.0%) 12 10 (5.4%) 0.309 Death 2 2 (1.4%) 3 3 (2.4%) 0.507 Dysphagia/Dysphonia 37 32 (17.4%) 26 23 (11.7%) 0.341 Gastrointestinal 72 49 (27.8%) 54 34 (27.2%) 0.389 Implant Displacement/

22 (1.0%)00 (0.0%) 0.200

Loosening Infection 65 43 (23.1%) 56 40 (28.1%) 0.669 Malpositioned Implant 2 2 (0.8%) 0 0 (0.0%) 0.179 Neck and/or Arm Pain 206 136 (61.0%) 175 112 (72.6%) 0.411 Neurological 128 88 (43.1%) 100 74 (43.8%) 0.888

Table 6: Time to Event Analysis of Adverse Events in Main Categories Up to 120 Month Interval (continued)

INV (N=242) CTR (N=221) P-Value

Events Subjects (n) (cumulative

rate %)

Events Subjects (n) (cumulative

rate %)

(Log-Rank Test)

Non-Union 1 1 (0.7%) 7 7 (3.4%) 0.019 Non-Union – Outcome Pending 0 0 (0.0%) 4 4 (1.9%) 0.034 Other 311 127 (60.8%) 187 90 (62.1%) 0.015 Other Pain 150 97 (51.2%) 156 99 (60.9%) 0.147 Respiratory 30 24 (12.8%) 22 21 (16.9%) 0.984 Spinal Event 137 95 (50.2%) 127 82 (54.6%) 0.792 Cervical Adjacent Non

66 (6.4%)99 (5.2%) 0.266

Contiguous Cervical Adjacent Contiguous 46 41 (22.5%) 60 51 (38.5%) 0.033 Cervical Target Level 38 33 (24.1%) 13 12 (7.3%) 0.006 Non-Cervical Level 47 40 (20.8%) 45 37 (24.4%) 0.713 Subsidence 0 0 (0.0%) 1 1 (0.5%) 0.293 Trauma 130 78 (40.3%) 72 46 (26.1%) 0.012 Urogenital 46 36 (20.9%) 39 29 (19.4%) 0.873 Vascular Injury Intra-Op 2 2 (0.8%) 3 3 (1.4%) 0.583

Table 7 summarizes the secondary interventions in the BRYAN® device and control treatment groups. Revisions, removals, and supplemental fixations occurring at or before the 24-month and 120-month follow-up visits were respectively considered second surgery failures for the IDE primary endpoint and PAS primary endpoint in the clinical study. Reoperations were not considered second surgery failures in the study. Table 8 also presents the Time to Event Analysis of Secondary Surgeries comparison

between the BRYAN

device and control treatment groups. As shown in this table, the rate of secondary surgeries at the index

level was 6.7% in the investigational group and 11.5% in the control group. For these safety comparisons, p-values less than

0.05 are considered statistically significant.

Table 7: Secondary Interventions and Surgical Procedures

Total ≤ 24 Months

Control

60 months

Control

6 Weeks

Invest.

Control

72 months

Invest.

Control

3 Months

Control

Invest.

84 months

Control

6 Months

Control

Invest.

96 months

Control

12 Months

Control

Invest.

108 months

Control

24 Months

Control

Invest.

≤ 120 months

36 Months

Control

Invest. # Patients (% of 242)

Total # Events

Invest. # Patients (% of 242)

Total #

Events

Total ≤ 120 Months

Control # Patients (% of 221)

Total # Events

Control

# Patients (% of 221)

Total # Events

Surgery

Invest.

Control

Revisions 10000000000000001 (0.4)10 (0.0)

Removals 00000010111002113 (1.2)33 (1.4)

Reoperations00000000002110103 (1.2)31 (0.5)

Supplemental Fixations

Other – Cervical Surgery

Other - Noncervical Spinal Surgery

00000001010004010 (0.0)06 (2.7)

00100010004225317 (2.9)87 (3.2)

000000121221650210 (4.1)109 (4.1)

48 months

Invest.

Control

Postoperative

Invest.

Revisions 10000000000000 1 (0.4)10 (0.0)

Removals 00131102010000 6 (2.5)611 (5.0)

Total ≤ 120 Months

48 months

Invest.

Reoperations101000000000006 (2.5)61 (0.5)

Supplemental Fixations

Other – Cervical Surgery

Other - Noncervical Spinal Surgery

Control

011000000000001 (0.4)17 (3.2)

1423322116100018 (7.4)2120 (9.0)

2465124401260120 (8.3)2529 (13.1)

60 months

Invest.

Control

72 months

Invest.

Control

84 months

Invest.

Control

96 months

Invest.

Control

108 months

Invest.

Control

≤ 120 months

Invest.

Control

Invest. # Patients (% of 242)

Total # Events

Control # Patients (% of 221)

Total # Events

Table 8: Time to Event Analysis of Secondary Surgeries Up to 120 Month Interval

INV (N=242) CTR (N=221) P-Value

(Log-Rank Test)

Any Second Surgery at Index

Events Subjects (n) (cumulative

rate %)

Events Subjects (n) (cumulative

rate %)

14 14 (6.7%) 20 18 (11.5%) 0.214

Level Revision 1 1 (0.4%) 0 0 (0.0%) 0.339 Removal 6 6 (2.9%) 11 11 (7.9%) 0.103 Supplemental Fixation 1 1 (0.5%) 8 7 (3.6%) 0.017 Reoperations 6 6 (2.8%) 1 1 (0.5%) 0.091 Supplemental Fixation - External

22 (1.0%)

Bone Growth Stimulator Other 245 109 (54.4%) 236 92 (60.4%) 0.933 Cervical Surgery 21 18 (9.8%) 24 20 (13.1%) 0.352 Non-cervical Spinal Surgery 25 20 (10.2%) 35 29 (21.1%) 0.050 Non-Spinal Surgery 199 92 (47.0%) 177 76 (51.8%) 0.771 Second surgeries involved with

25 21 (11.3%) 37 29 (18.8%) 0.054 adjacent levels and/or levels second to adjacent Levels

Second surgeries involved with

22 19 (9.7%) 32 24 (15.8%) 0.146 adjacent levels

Enhanced Surveillance Safety Results

Information on the cumulative total MDRs (n=25) and device sales has been collected and evaluated for the five-year time period after PMA approval. During the 60-month study period, no unanticipated adverse events were identified, and the device has not been withdrawn from any of the markets due to safety concerns.

Effectiveness Results

Primary Effectiveness Analysis

The primary endpoint for both the IDE and post-approval studies was a composite of the following parameters: pain and functional disability, neurological status, adverse events, and secondary surgical interventions. This was termed overall success.

In the approved protocol, individual subject success (i.e., overall success) was defined as attainment of all of the following:

▪ An improvement of at least 15 points from the baseline Neck Disability Index (NDI) score. ▪ Maintenance or improvement in each evaluated neurological status parameter as compared to the pre-operative baseline

score for motor function, sensory function and reflexes.

▪ No serious adverse event classified as implant-associated or implant/surgical procedure-associated. ▪ No additional surgical procedure classified as “Failure”.

Overall success was determined at the 24-month time point for the IDE and the 120-month time point for the post-approval study.

Overall Success Summary

Study success was expressed as the number of individual subjects categorized as a success divided by the total number of subjects evaluated. Table 9 describes the success rates and p-values for the comparison of individual outcome parameters and

overall success. Observed success rates are the 24-month and 120-month outcomes of the clinical trial. The p-values were calculated using the z-test of the normal approximation to the binomial distributions with the standard error derived from using the Farrington-Manning Method to assess both the non-inferiority and superiority hypotheses. The conclusions were based on the analysis which was pre-defined in the protocol.

Table 9: Observed Success Rates at 24 and 120 Months and P-Values for the Comparison of Success Rates Between the Two Groups

Primary Outcome

Variable

NDI 197/229

Neurological 215/229

Serious, Related Adverse Event Failure*

2nd Intervention Failure* 4 5 n/a n/a 8 8 n/a n/a

Overall Success 190/230

24-Month Observed Success Rate P-Values for the Comparison of 24-Month Results 120-Month Observed Success Rate 120-Month Posterior Probabilities

Inv Ctrl Non-inferiority Superiority Inv Ctrl Non-inferiority Superiority

(86.0%)

(93.9%)

45 n/a n/a 910n/an/a

(82.6%)

153/194 (78.9%)

175/194 (90.2%)

142/194 (73.2%)

< 0.001 0.026 114/126

< 0.001 0.08 116/126

< 0.001 0.01 104/128

(90.5%)

(92.1%)

(81.3%)

78/103

(75.7%)

98/103

(95.1%)

69/104

(66.3%)

< 0.001 0.001

0.023 0.826

< 0.001 0.005

* The demonimators for these rates are given as the total number of patients due to the cumulative nature of these events. In Table 9, the clinical evaluation visit dates were used as the back end of the windows, whereas Tables 4 and 5 utilized wider, continuous time windows. Therefore, the events included in Table 9 may appear to differ from those in Tables 4 and 5.

Non-inferiority of the BRYAN success at both 24 and 120 months as listed in Table 9. Statistical superiority of the BRYAN

disc group to the control group was demonstrated for NDI, neurological status, and overall

disc group to the control group was demonstrated for overall success and the NDI variable for the specifically defined population studied in the clinical trial at both 24 months and 120 months postoperatively. The neurological component was not found to be statistically superior in the

BRYAN

group at these time points even though it did achieve non-inferiority at both time points.

Sensitivity Analyses

To examine the effect of unknown outcomes on study conclusions, sensitivity analyses were conducted by imputing possible overall success outcomes for the missing patients. All analyses, even the worst-case assumptions, demonstrated at least non-

inferiority of the BRYAN

Cervical Disc to the fusion control in Overall Success.

Secondary Effectiveness Analysis

The secondary endpoints assessed were Neck Pain, Arm Pain, SF-36 Health Survey, Gait Assessment, Foraminal Compression, Work Status, Patient Satisfaction, Radiographic endpoints, Global Perceived Effect (patient’s overall assessment of study treatment effectiveness as a function of pain), and Doctor’s Perception (investigator’s perception of patient’s condition). Radiographic endpoints include FSU height/implant subsidence; anteroposterior implant migration; treated level angular motion in flexion, extension, and side bending; and translational motion. Fusion measurements replaced motion measurements in control patients.

Radiographic Assessments

For patients receiving the BRYAN® device, the mean angular range of motion values at 24 and 120 months postoperative, respectively, were 8.08° (n=222) and 8.69° (n=126) as compared to a preoperative value of 6.45° (n=215). The range of motion

values measured from flexion/extension radiographs at 24 and 120 months for the BRYAN histograms below. This histograms used values obtained by rounding recorded range of motion for each subject to the nearest integer.

Figure 1: Histogram of BRYAN

Cervical Disc Angular Range of Motion at 24 Months

device patients are presented in the

Figure 2: Histogram of BRYAN® Cervical Disc Angular Range of Motion at 120 Months

An analysis of the correlation between the degree of segmental motion and pain was also performed, and no statistically significant correlations were noted.

At 120 months, 7.4% (9/122) investigational subjects had Grade III heterotopic ossification (HO), and 6.6% (8/122) had Grade IV HO. The incidence of HO increased and worsened over time with resultant loss motion. BRYAN

observed in two investigational subjects (one at 60 months and another at 120 months).

implant migration was

Conclusions Drawn from the Study Data

In summary, the overall success rate for the investigational group at 24 and 120 months was found to be not only statistically non-inferior to the control group rate, but also superior. Therefore, the primary clinical study objective was met, thus indicating

that the BRYAN intractable radiculopathy or myelopathy or the cervical spine.

Cervical Disc is as safe and effective in the long term as the current standard of care for treating patients with

PACKAGING

Packages for each of the components should be intact upon receipt. If a loaner or consignment system is used, all sets should be carefully checked for completeness and all components including instruments should be carefully checked to ensure there is no damage prior to use. Damaged packages or products should not be used, and should be returned to Medtronic.

CLEANING AND DECONTAMINATION

Implants are supplied sterile from Medtronic and should be used directly from the sterile package. Implants should not be cleaned or decontaminated by the user. Unless just removed from an unopened Medtronic package, all instruments must be disassembled (if applicable), cleaned using neutral or enzymatic cleaners prepared per manufacturer’s instructions before sterilization, introduction into a sterile surgical field, or (if applicable) before returning the product to Medtronic. Cleaning and disinfecting of instruments can be performed with aldehyde-free solvents at higher temperatures. Cleaning and decontamination must include the use of neutral cleaners followed by a deionized water rinse. This should be performed as soon as reasonably practical following use to minimize the potential of drying prior to cleaning.

Instrument Cleaning

When cleaning instruments by hand, the following should be observed:

1. Clear any corners or recesses of all debris (Note: extra care should be taken to clean out any cannulated areas by using an

appropriate cleaning stylet and rinsing immediately).

2. Remove all traces of blood and other such residues as soon as reasonably practical following use to minimize the potential

of drying.

3. The instruments should be submerged and cleaned with a commercially available manual cleaner (i.e., Terg-A-Zyme from

ALCONOX, Inc.) prepared according to the manufacturer’s recommendation.

4. Scrub the device while immersed in the cleaning solution with a soft nylon brush for a minimum of one minute, giving special

attention to threads, crevices, and hard to reach areas until visibly clean. During cleaning, actuate device.

5. The instrument should be thoroughly rinsed after cleaning for a minimum of one minute with fresh deionized or tap water.

Repeat process if visual inspection warrants repeat cleaning.

Note: certain cleaning solutions such as those containing formalin, glutaraldehyde, bleach and/or other alkaline cleaners may damage some devices, particularly instruments. These solutions should not be used. Also, many instruments require disassembly before cleaning.

All products should be treated with care. Improper use or handling may lead to damage and/or possible improper functioning of the device.

STERILIZATION

Implants are supplied sterile from Medtronic and should be used directly from the sterile package. Unless marked sterile and clearly labeled as such in an unopened sterile package provided by the company, instruments used in surgery

must be sterilized by the hospital prior to use. Remove all packaging materials prior to sterilization. Only sterile products should be placed in the operative field. Unless specified elsewhere, these products are recommended to be steam sterilized by the hospital using the process parameters listed in Table 10.

Table 10: Sterilization Cycle Parameters for the United States and Its Territories

METHOD CYCLE TEMPERATURE EXPOSURE TIME DRY TIME

Steam Pre-Vacuum 270°F (132°C) 4 Minutes 30 Minutes

NOTE: Because of the many variables involved in sterilization, each medical facility should calibrate and verify the sterilization process (e.g., temperatures, times) used for their equipment. It is the responsibility of the end user to ensure the available equipment (sterilizer and accessories including appropriate sterilization indicators and wraps, as applicable) is compatible with the set of parameters listed in Table 10.

Remove all packaging material prior to sterilization. Only sterile implants and instruments should be used in surgery. No implant should be re-used once it comes into contact with human tissue or body fluid. Always immediately clean and re-sterilize instruments used in surgery. This process must be performed before handling or (if applicable) returning the product to Medtronic.

PRODUCT COMPLAINTS

Any health care professional (e.g., customer or user of this system of products) who has any complaints or who has experienced any dissatisfaction in the product quality, identity, durability, reliability, safety, effectiveness, and/or performance, should notify the distributor or Medtronic. Further, if any of the implanted spinal system component(s) ever “malfunctions” (i.e., does not meet any of its performance specifications or otherwise does not perform as intended), or is suspected of doing so, the distributor should be notified immediately. If any Medtronic product ever malfunctions and may have caused or contributed to the death or serious injury of a patient, the distributor should be notified immediately by telephone, fax, or written correspondence. When filing a complaint, provide the component(s) name and number, lot number(s), your name and address, the nature of the complaint, and notification of whether or not a written report from the distributor is requested.

FURTHER INFORMATION

Recommended directions for use of this system (surgical operative techniques) are available at no charge upon request. If further information is needed or required, contact Medtronic.

DEVICE RETRIEVALS

Should it be necessary to remove a BRYAN® Cervical Disc device, call Medtronic prior to the scheduled surgery for product/ tissue retrieval information. Refer to the BRYAN

technique for device retrieval and instructions for returning the explanted device to Medtronic. All explanted devices must be returned to Medtronic for analysis.

Medtronic Sofamor Danek USA, Inc.

1800 Pyramid Place Memphis, TN 38132 Telephone: 800 933 2635 (USA)

901 396 3133 (Outside USA)

Fax: 901 396 0356

EXPLANATION OF SYMBOLS

For US audiences only

CAUTION: Federal law (USA) restricts these devices to sale by or on the order of a physician.

Consult instructions for use

Cervical Disc Surgical Technique for step-by-step instructions on the required

Do not re-use

Batch code

Manufacturer

Catalogue number

Sterilized using ethylene oxide

Sterilized using irradiation

Use-by date

MR Conditional

Medtronic 6470318 Instructions for Use

Specifications and Main Features

Frequently Asked Questions

User Manual