← Product Code MJO · P090029 # PRESTIGE LP CERVICAL DISC (P090029) _Medtronic Sofamor Danek USA, Inc. · MJO · Jul 24, 2014 · Orthopedic · APPR_ **Canonical URL:** https://fda.innolitics.com/device/P090029 ## Device Facts - **Applicant:** Medtronic Sofamor Danek USA, Inc. - **Product Code:** MJO - **Decision Date:** Jul 24, 2014 - **Decision:** APPR - **Device Class:** Class 3 - **Review Panel:** Orthopedic - **Attributes:** Therapeutic ## Intended Use The PRESTIGE® LP Cervical Disc is indicated in skeletally mature patients for reconstruction of the disc at one level from C3-C7 following single-level discectomy for intractable radiculopathy (arm pain and/or a neurological deficit) with or without neck pain, or myelopathy due to a single-level abnormality localized to the level of the disc space and at least one of the following conditions confirmed by imaging (CT, MRI, X-rays): herniated nucleus pulposus, spondylosis (defined by the presence of osteophytes), and/or visible loss of disc height as compared to adjacent levels. The PRESTIGE® LP Cervical Disc is implanted using an anterior approach. Patients should have failed at least 6 weeks of non-operative treatment or have had the presence of progressive symptoms or signs of nerve root/spinal cord compression in the face of continued non-operative management prior to implantation of the PRESTIGE® LP Cervical Disc. ## Device Story The PRESTIGE® LP Cervical Disc is a two-piece, ball-and-trough articulating implant designed for single-level cervical disc replacement. It is inserted via an anterior approach by a surgeon. The device consists of two titanium-ceramic composite plates; the superior plate features a ball and the inferior plate a trough, creating an interface that allows for motion. The plates are secured to adjacent vertebral bodies using rail geometries with anti-migration teeth and a plasma-sprayed titanium coating to promote bony on-growth. The device is used in a clinical setting to treat intractable radiculopathy or myelopathy. By replacing the diseased disc while preserving segmental motion, the device aims to reduce pain and neurological deficits, potentially offering an alternative to fusion. Healthcare providers evaluate the device's performance through clinical assessments and radiographic imaging to monitor for subsidence, migration, or heterotopic ossification. ## Clinical Evidence Prospective, multi-center, non-randomized, unmasked, non-inferiority trial (IDE #G040086) comparing PRESTIGE® LP (n=280) to historical ACDF control (n=265). Primary endpoint: composite success (NDI improvement ≥15, neurological maintenance/improvement, FSU height success, no serious implant-related AE, no secondary surgery failure). At 24 months, PRESTIGE® LP overall success (without FSU) was 79.3% vs 66.8% for control (posterior probability of non-inferiority ~100%). Neurological success was 93.3% (IDE) vs 83.6% (control). Adverse event rates were higher in the IDE cohort, attributed to higher follow-up rates. ## Technological Characteristics Two-piece articulating artificial cervical disc. Materials: Titanium-6Aluminum-4Vanadium with 10% Titanium Carbide; plasma-sprayed commercially pure titanium (CP Ti) coating. Mechanism: Ball and trough interface. Fixation: Rail geometries with anti-migration teeth. Sterilization: Gamma radiation (min 25 kGy, SAL 10⁻⁶). Dimensions: Various sizes (6-8mm height, 12-18mm footprint). ## Reference Devices - PRESTIGE® Cervical Disc (G010188) - Atlantis® anterior cervical plate ## Submission Summary (Full Text) > This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com. > > Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a PMA](https://innolitics.com/services/regulatory/), [a 510(k)](https://innolitics.com/services/510ks/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/). {0} SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) I. GENERAL INFORMATION Device Generic Name: Artificial Cervical Disc Device Trade Name: PRESTIGE® LP Cervical Disc Device Procode: MJO Applicant's Name and Address: Medtronic Sofamor Danek 1800 Pyramid Place Memphis, TN 38132 Date of Panel Recommendation: None Premarket Approval Application (PMA) Number: P090029 Date of FDA Notice of Approval: July 24, 2014 II. INDICATIONS FOR USE The PRESTIGE® LP Cervical Disc is indicated in skeletally mature patients for reconstruction of the disc at one level from C3-C7 following single-level discectomy for intractable radiculopathy (arm pain and/or a neurological deficit) with or without neck pain, or myelopathy due to a single-level abnormality localized to the level of the disc space and at least one of the following conditions confirmed by imaging (CT, MRI, X-rays): herniated nucleus pulposus, spondylosis (defined by the presence of osteophytes), and/or visible loss of disc height as compared to adjacent levels. The PRESTIGE® LP Cervical Disc is implanted using an anterior approach. Patients should have failed at least 6 weeks of non-operative treatment or have had the presence of progressive symptoms or signs of nerve root/spinal cord compression in the face of continued non-operative management prior to implantation of the PRESTIGE® LP Cervical Disc. III. CONTRAINDICATIONS The PRESTIGE® LP Cervical Disc should not be implanted in patients with the following conditions: - Active systemic infection or localized infection at the surgical site - Osteoporosis defined as a DEXA bone mineral density T-score equal to or worse than -3.5 or a T-score equal to or worse than -2.5 with vertebral compression fracture, or osteopenia defined as a DEXA bone mineral density T-score ≤ -1.0 - Allergy or sensitivity to titanium, aluminum or vanadium - Marked cervical instability on neutral resting lateral or flexion/extension radiographs; translation >3.5mm and/or >11° rotational difference from that of either adjacent level PMA P090029: FDA Summary of Safety and Effectiveness Data {1} - Severe spondylosis at the level to be treated, characterized by bridging osteophytes, loss of disc height $>50\%$ , an absence of motion $(<2^{\circ})$ as this may lead to a limited range of motion and may encourage bone formation (e.g. heterotopic ossification, fusion) - Severe facet joint arthropathy - Significant cervical anatomical deformity or clinically compromised vertebral bodies at the affected level due to current or past trauma (e.g., by radiographic appearance of fracture callus, malunion or nonunion) or disease (e.g., ankylosing spondylitis, rheumatoid arthritis) Significant kyphotic deformity or significant reversal of lordosis; or - Symptoms attributed to more than one cervical level # IV. WARNINGS AND PRECAUTIONS The warnings and precautions can be found in the PRESTIGE® LP Cervical Disc labeling. # V. DEVICE DESCRIPTION The PRESTIGE® LP Cervical Disc is a two-piece articulating device that is inserted into the intervertebral disc space as a single unit at a single cervical level using an anterior approach. The device is manufactured from a titanium ceramic composite (Titanium-6Aluminum-4Vanadium with $10\%$ Titanium Carbide) and consists of two metal plates which function via a ball and trough mechanism. The superior component of the implant contains the ball portion of the mechanism, and the inferior component contains the trough portion. These two features engage to create an interface designed to allow for motion after implantation. Each component is affixed to the adjacent vertebral body by two rail geometries incorporating anti-migration teeth which are press fit into two pre-drilled holes in the vertebral bone. The portion of the flat surface between the rails and contacting the vertebral endplate contains commercially pure titanium (CP Ti) plasma thermal sprayed coating designed to permit bony on-growth for additional device incorporation. The remaining portion of the flat surface is titanium ceramic roughened to enhance fixation. ![img-0.jpeg](img-0.jpeg) PMA P090029: FDA Summary of Safety and Effectiveness Data {2} PRESTIGE® LP implants are offered in a variety of configurations to accommodate varied patient anatomy. The available components are shown in Table 1 below. Table 1: PRESTIGE® LP Cervical Disc Device Sizes | Catalog Number | Size | | --- | --- | | 6972260 | 6mm x 12mm | | 6972460 | 6mm x 14mm | | 6972660 | 6mm x 16mm | | 6972860 | 6mm x 18mm | | 6972470 | 7mm x 14mm | | 6972670 | 7mm x 16mm | | 6972870 | 7mm x 18mm | | 6972480 | 8mm x 14mm | | 6972680 | 8mm x 16mm | | 6972880 | 8mm x 18mm | PRESTIGE® LP devices are implanted using instruments specific to the device, as well as manual surgical instruments. Instruments specifically designed for implanting PRESTIGE® LP consist of trials, trial cutter guides, rail punches, and implant inserters. General purpose instruments include instruments for cervical distraction and discectomy preparation. VI. ALTERNATIVE PRACTICES AND PROCEDURES There are several other alternatives for the treatment of intractable radiculopathy or myelopathy due to a single-level abnormality localized to the disc space. - Nonoperative alternative treatments include, but are not limited to, physical therapy, medications, braces, chiropractic care, bed rest, spinal injections, or exercise programs. - Surgical alternatives include, but are not limited to, surgical decompression and/or fusion using various bone grafting techniques (e.g., Cloward bone dowels, Smith Robinson tri-cortical wedges, and Keystone grafts) or interbody fusion devices, which may or may not be used in conjunction with anterior cervical plating (e.g., plate and screws), or posterior spinal systems (e.g., rods, hooks, wires). Anterior cervical discectomy and fusion (ACDF) with an interbody graft or spacer is the most commonly used method for decompression and fusion. Intractable radiculopathy or myelopathy due to a single-level abnormality localized to the disc space may also be treated surgically using another FDA approved artificial cervical disc. Each alternative has advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician. VII. MARKETING HISTORY The device has a marketing history outside of the United States that began in 2004, and has not been withdrawn from marketing for any reason. The PRESTIGE® LP Cervical Disc device is marketed in: Argentina, Australia, Austria, Belgium, Brazil, Canada, Czech Republic, Chile, China, Costa Rica, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Jamaica, Malaysia, Mexico, Netherlands, New Zealand, Norway, Pakistan, Poland, PMA P090029: FDA Summary of Safety and Effectiveness Data Page 3 of 79 {3} Portugal, Saudi Arabia, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey and the United Kingdom. ## VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH Below is a list of the potential adverse effects (e.g., complications) associated with the use of the PRESTIGE® LP Cervical Disc. 1. Risks associated with any surgical procedure include: abscess; cellulitis; wound dehiscence; wound, local, and/or systemic infection; wound necrosis; edema; hematoma; heart and vascular complications; hypertension; thrombosis; ischemia; embolism; thromboembolism; hemorrhage; thrombophlebitis; adverse reactions to anesthesia; pulmonary complications; organ, nerve or muscular damage; gastrointestinal or genitourinary compromise; seizure, convulsion, or changes to mental status; complications of pregnancy including miscarriage and fetal birth defects; inability to resume activities of daily living including loss of consortium; and death. 2. Risks associated with anterior cervical spine surgery include: dysphagia; dysphonia; hoarseness; vocal cord paralysis; laryngeal palsy; sore throat; recurring aspirations; tracheal, esophageal, or pharyngeal perforation; airway obstruction; warmth or tingling in the extremities; neurologic complications including damage to nerve roots, other nerves, or the spinal cord possibly resulting in weakness, pain or even paralysis; dural tears or leaks; cerebrospinal fistula; discitis, arachnoiditis, and other types of inflammation; loss of disc height; loss of anatomic sagittal plane curvature or vertebral listhesis; scarring, herniation or degeneration of adjacent discs; surrounding soft tissue damage, spinal stenosis; spondylolysis; fistula; vascular damage and/or rupture; and headache. 3. Risks associated with a cervical artificial disc device, including the PRESTIGE® LP Cervical Disc, include: early or late loosening of the components; disassembly; bending or breakage of any or all of the components; implant migration; implant malpositioning; implant subsidence; loss of fixation; sizing issues with components; anatomical or technical difficulties; bone fracture; foreign body reaction to the implant including possible tumor formation, autoimmune disease, metallosis, and/or scarring; possible tissue reaction; bone resorption; bone formation (including heterotopic ossification) 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 or placement of implants or instruments; bending or breakage of a surgical instrument, as well as the possibility of a fragment of a broken instrument remaining in the patient; loss of neurological function; decreased strength of extremities; decreased reflexes; cord or nerve root injury; loss of bowel and/or bladder control or other types of urological system compromise; interference with radiographic imaging because of the presence of the implant; and the need for subsequent surgical intervention. For the specific adverse events that occurred in the clinical study of the PRESTIGE® LP Cervical Disc, please see Section X below. PMA P090029: FDA Summary of Safety and Effectiveness Data Page 4 of 79 {4} IX. SUMMARY OF PRECLINICAL STUDIES A variety of testing was conducted to characterize the performance of the PRESTIGE® LP Cervical Disc, as follows: A. Laboratory Studies - Subluxation Testing - Subsidence Testing - Push-Out - Static Compression - Compression Fatigue - Static Compression Shear - Compression Shear Fatigue - Durability and Wear Testing - MRI Testing B. Animal Testing - Wear Particulate Injection Analysis C. Additional Studies - Biocompatibility - Sterilization, Packaging, and Shelf Life Testing PMA P090029: FDA Summary of Safety and Effectiveness Data Page 5 of 79 {5} # A. Laboratory Studies Table 2: Mechanical Testing | Test Description | Purpose | Methods | Medtronic's Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | Subluxation 1 | To determine the amount of shear force applied to the inferior component required to dislocate (subluxate) the superior "ball" feature from the "trough" feature in multiple directions and lordotic angulations. | Under 100N preload, Components (n=1 assembly test puck) were tested in both the M-L and AP directions. M-L specimens were held in two relative positions 0° and 10°. A-P specimens were held in 10° flexion. In both configurations the inferior component of each specimen was displaced laterally in multiple directions until the superior component (ball) was displaced from the inferior component (trough). | The subluxation force must be greater than the maximum in vivo shear load in the cervical spine (20N).1 | The mean maximum subluxation force was 357±8.3 N at 0°; 321±17.6 N at 10° positive lateral bending, and 769±82 N at 10° negative lateral bending; 683±116.0 N at 10° flexion and 276±43.6 N at 10° extension. In all instances, the PRESTIGE® LP disc subluxation values exceeded the clinically acceptable value of 20 N. These results suggest that the device can resist subluxation loads that exceed anticipated physiologic loads on the cervical spine. | | Subluxation 2 | To determine what amount of shear force applied to the inferior component required to dislocate (subluxate) the superior "ball" feature from the "trough" feature in multiple directions and angulations. | Under 100N preload, n=6 (6mm x 16 mm) device assemblies were tested in both the M-L and AP directions. M-L specimens were held in two relative positions 0° and 10°. A-P specimens were held in 10° flexion. In both configurations the inferior component of each specimen was displaced laterally in positive and negative directions until the superior component (ball) was displaced from the inferior component (trough). | The medial-lateral and flexion-extension subluxation forces must exceed 20N.1 | The mean maximum medial-lateral subluxation force was 246.2±16.0N at 0°; 360.5±21.0N at 10° positive lateral bending, and 73.7±4.5N at 10° negative lateral bending; 406.9±37.9N at 10° flexion and 93.2±11.9N at 10° extension. In all instances, the PRESTIGE® LP disc subluxation values exceeded the clinically acceptable value of 20 N. These results suggest that the device can resist subluxation loads that exceed anticipated physiologic loads on the cervical spine. | PMA P090029: FDA Summary of Safety and Effectiveness Data {6} PMA P090029: FDA Summary of Safety and Effectiveness Data Page 7 of 79 | Test Description | Purpose | Methods | Medtronic’s Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | Subsidence | To determine whether the PRESTIGE® LP implant can effectively withstand a static axial compressive load without subsiding (sinking) into the vertebral body endplates, which in vivo would potentially cause endplate fracture, instability, and/or pain at the implanted level. | n=1 (6mm x 12 mm) device assembly was assembled to mating foam blocks and axial load is applied at 0.1 mm/sec until the blocks contacted. Load/displacements were recorded for 5 repetitions of the test. | The subsidence force must be greater than the maximum in vivo compressive load in the cervical spine (74N) due to head weight^{1} and equivalent to the stiffness of the previously approved PRESTIGE® Cervical Disc (363 N/mm). | The mean ultimate load was 513±28.6N with a stiffness value of 442±19.1 N/mm. The average subsidence values were higher than the clinically acceptable value of 74N and PRESTIGE® Cervical Disc (363 N/mm). These results suggest that the device can resist subsidence loads that exceed anticipated physiologic loads on the cervical spine. | | Push-Out | To determine overall resistance to push-out for the PRESTIGE® LP device | A 100 N preload was applied to n=1 (6mm x 12mm) device assembly while an axial force is applied in the anterior/posterior and medial lateral directions at 6 mm/min until failure is obtained. | The pushout force must be greater than the maximum in vivo intervertebral shear force in the cervical spine (20N).^{1} | The mean ultimate load was 127.4±3.2N. The results exceeded the clinically acceptable load of 20N. These results suggest that the device can resist push-out loads that exceed anticipated physiologic loads on the cervical spine. | | Static Compression 1 | To characterize the PRESTIGE® LP device’s ability to provide resistance to axial compressive loading | n=5 (7mm x 18 mm) device assemblies were placed between two unsupported stainless steel test blocks, and an axial compressive load was applied at 3mm/min until functional failure occurred. | The axial compressive failure load must exceed the clinically acceptable value of 74N.^{1} | The mean failure load was 8808±2233N. The results of the static compression test far exceeded the clinically acceptable load of 74N. These results suggest that the device can resist compressive loading that exceeds anticipated physiologic loads on the cervical spine. | {7} PMA P090029: FDA Summary of Safety and Effectiveness Data Page 8 of 79 | Test Description | Purpose | Methods | Medtronic’s Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | Static Compression 2 | To characterize the 6x18mm PRESTIGE® LP device’s ability to withstand axial compressive loads by determining the ultimate failure load of the construct over multiple specimens | n=6 (6mm x 18mm) device assemblies were tested in accordance with ASTM Standard F2346 “Standard Test Method for Static and Dynamic Characterization of Spinal Artificial Discs” | The mean ultimate load for the 6x18mm PRESTIGE® LP implant was greater than or equal to 550N. This load is twice the acceptance criterion of the fatigue load and a factor of safety six times the compression load in the cervical spine due to the weight of the head (74N).^{1} | The maximum load was 7992±748N and a stiffness of 21,096 N/mm. The results of the static compression test exceeded the clinically acceptable load of 74N as well as the 550N load. These results suggest that the device can resist compressive loading that exceeds anticipated physiologic loads on the cervical spine. | | Compression Fatigue 1 | To characterize the PRESTIGE® LP device’s ability to provide resistance to axial compressive loading throughout the device’s life cycle. | n=3 (7mm x 18mm) devices assemblies were placed between two polyethylene test blocks. They were then tested on an MTS machine in load control with an R value of 10 and a cyclical load of 225N until attainment of 5M cycles or failure of the component. | The compression fatigue force must exceed the clinically acceptable value of 74N.^{1} | All three specimens ran out at 10 million cycles at an applied load of 225N. Results from the compression fatigue tests exceeded the clinically acceptable load of 74N. These results suggest that the device can resist dynamic compressive loading that exceeds anticipated physiologic loads on the cervical spine. | {8} PMA P090029: FDA Summary of Safety and Effectiveness Data Page 9 of 79 | Test Description | Purpose | Methods | Medtronic's Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | Compression Fatigue 2 | To characterize the 5x12mm and 5x16mm PRESTIGE® LP device’s ability to provide resistance to axial compressive loading throughout a device’s life cycle. | n=2 (5mm x 12mm) device assemblies were tested in accordance with ASTM Standard F2193 “Standard Specifications and Test Methods for Components Used in the Surgical Fixation of the Spinal Skeletal System.” | The assemblies must attain two run outs at 10 million cycles at a compressive fatigue load of 225N without functional failure which represents a three times factor of safety of the compression load in the cervical spine due to the weight of the head (74N).^{1} | All assemblies ran out at 10 million cycles at an applied load of 225N. Results from the compression fatigue tests far exceeded the clinically acceptable load of 74N and met the acceptance criterion as defined in the test protocol. These results suggest that the device can resist compressive loading that exceeds anticipated physiologic loads on the cervical spine. | | Compression Fatigue 3 | To characterize the 6x18mm PRESTIGE® LP device’s ability to provide resistance to axial compressive loading throughout a device’s life cycle. | n=2 (6mm x 18mm) device assemblies were tested in accordance with ASTM Standard F2346 “Standard Test Method for Static and Dynamic Characterization of Spinal Artificial Discs.” | The assemblies must attain two run outs at 10 million cycles at a compressive fatigue load of 225N without functional failure which represents a three times factor of safety of the compression load in the cervical spine due to the weight of the head (74N).^{1} | Both assemblies ran out at 10 million cycles at an applied load of 225N. Results from the compression fatigue tests far exceeded the clinically acceptable load of 74N and met the acceptance criterion as defined in the test protocol. These results suggest that the device can resist compressive loading that exceeds anticipated physiologic loads on the cervical spine. | {9} PMA P090029: FDA Summary of Safety and Effectiveness Data Page 10 of 79 | Test Description | Purpose | Methods | Medtronic's Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | Static Compression Shear | To characterize the device’s ability to resist shear compressive loads found during day-to-day physiologic loading of the cervical spine. | n=6 (5mm x 16mm) device assemblies were tested in accordance with ASTM Standard F2346 “Standard Test Method for Static and Dynamic Characterization of Spinal Artificial Discs.” | The assemblies must attain at least a 550N compressive load prior to functional failure for all six samples which represents a six times factor of safety of the compression load in the cervical spine due to the weight of the head (74N).^{1} | The mean maximum static compression shear load was 4962±674N with a mean stiffness of 6058±762N. The average ultimate load for all PRESTIGE® LP components exceeds the clinically acceptable load of 74N and the defined acceptance criteria of 550N. These results suggest that the device can resist compressive shear loading that exceeds anticipated physiologic loads on the cervical spine. | | Compression Shear Fatigue | To characterize the device’s ability to resist shear compressive loads found during day-to-day physiologic loading of the cervical spine. | n=2 (5mm x 12 mm) device assemblies were tested in accordance with ASTM Standard F2346 “Standard Test Method for Static and Dynamic Characterization of Spinal Artificial Discs.” | The assemblies must attain two run outs at 10 million cycles without functional failure at a minimum compressive load of 225N which represents a three times factor of safety of the compression load in the cervical spine due to the weight of the head (74N).^{1} | The assemblies ran out at 10 million cycles at a maximum compression shear axial load of 225N and maximum calculated shear load of 159N. Results from the compression fatigue tests far exceeded the clinically acceptable load of 74N and met the acceptance criterion as defined in the test protocol. These results suggest that the device can resist dynamic compressive shear loading that exceeds anticipated physiologic loads on the cervical spine. | {10} Table 3: Wear Testing | Test Description | Purpose | Methods | Medtronic’s Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | Wear Test 1 (Lateral bending coupled with axial rotation followed by flexion/extension) | To characterize the wear behavior for the PRESTIGE® LP family of implants. | n=6 (6mm x 16mm) device assemblies were tested in accordance with ASTM 2423 “Functional, Kinematic, and Wear Assessment of Total Disc Prostheses.” | The wear rate under combined motion for the PRESTIGE® LP device must not be statistically higher than wear rate for hard bearing cervical disc replacements (1.10±0.09.mm³/MC). | The steady-state wear rate under combined motion for the PRESTIGE® LP Device was 0.35±0.03mm³/MC with a mean particle diameter of <0.2μm. The total wear at 20MC was 4.22±0.21mm³. The overall steady-state wear rate for the PRESTIGE® LP device was lower than that of other hard bearing cervical disc replacements, and met the acceptance criterion as defined in the test protocol. The wear rate and volume and size of particulate wear debris are similar to other legally-marketed hard bearing cervical disc replacements. | | Wear Test 2 (Lateral bending combined with axial rotation and flexion/extension) | To characterize the wear behavior for the PRESTIGE® LP family of implants | n=6 (6mm x 16mm) device assemblies were tested in accordance with ISO 18192-1 “Implants for Surgery – Wear of Total Intervertebral Spinal Disc Prostheses – Part 1: Loading and Displacement Parameters for Wear Testing and Corresponding Environmental Conditions for Test. | This test was used to generate benchmark volumetric wear and wear rate data under the ISO standard, and there was no acceptance criteria quantified. | The steady-state wear rate was 0.25±0.04mm³/MC The total accumulated wear was 2.74±0.38mm³ Characterization only. | PMA P090029: FDA Summary of Safety and Effectiveness Data {11} PMA P090029: FDA Summary of Safety and Effectiveness Data Page 12 of 79 | Test Description | Purpose | Methods | Medtronic’s Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | Wear Test 3 (Lateral bending coupled with axial rotation followed by flexion/extension; Flexion/extension followed by lateral bending coupled with axial rotation) | To characterize the wear behavior for the PRESTIGE® LP family of implants under simulated loading of the cervical spine. | n=6 device test coupons (three in each sequence) were tested in coupled Lateral Bending and axial rotation followed by flexion/extension, and three were tested in reverse order with flexion/extension cycles first. Coupled motion was tested to 5.0 million cycles (MC) with a compressive load of 49N. Flexion/extension of 9.7° was tested to 10.0 MC with a compressive load of 148N. Combined motion testing was conducted in lateral bending at 4.7° and axial rotation at 3.8°. All specimen were tested in a temperature controlled both with a fluid medium of 25% alpha calf fraction. | All implants must be functional by allowing a total of ±4.7° lateral bending (LB) coupled with ±3.8° axial rotation (AR) followed by ±9.7° flexion/extension (FE). Furthermore, none of the inferior side components must wear through from the bottom of the trough feature to the test coupon. | All test components remained functional after 15.0 MC in all three motions. Therefore, the acceptance criteria were met. The total volumetric wear after 15 MC when testing first in lateral bending plus axial rotation and then flexion-extension was 1.25±0.89mm³. The total volumetric wear after 15 MC when testing in flexion-extension first and then lateral bending plus axial rotation was 1.32±0.71mm³. The mean steady-state wear rate when testing first in lateral bending plus axial rotation and then flexion-extension was 0.27±0.31mm³/MC for lateral bending plus axial rotation and was 0.01mm²±0.00mm³/MC in flexion-extension. The mean steady-state wear rate when testing when testing in flexion-extension first and then lateral bending plus axial rotation was 0.21±0.18mm³/MC for lateral bending plus axial rotation and was 0.01mm²±0.01mm³/MC in flexion-extension. These results suggest that the device will not wear through during expected physiological use. | {12} PMA P090029: FDA Summary of Safety and Effectiveness Data Page 13 of 79 | Test Description | Purpose | Methods | Medtronic’s Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | Wear Test 4 (Lateral bending coupled with axial rotation for high and low radial clearances) | To characterize the influence of radial clearance on the wear behavior of the PRESTIGE® LP Cervical Disc. | n=6 (n=3 high clearance; n=3 low clearance) device assemblies were tested in accordance with ASTM 2423 “Functional, Kinematic, and Wear Assessment of Total Disc Prostheses” | The steady-state wear rate for both the high and low clearances are statistically equivalent or lower than the specimen’s nominal steady-state wear rate. (0.41±0.06.mm³/MC). | The steady-state wear rate at low clearance was 0.45±0.05 mm³/MC and 0.28±0.17 mm³/MC at high clearance. The volumetric wear for 5 MC at low clearance was 2.41±0.38 mm³ and 1.52±0.92 mm³ at high clearance. There was no statistically-significant difference between the steady-state wear rate of the low-clearance and the nominal specimens (p = 0.381) and between the high-clearance specimens and the nominal specimens (p = 0.107). These results suggest that the device has similar wear rates as other legally-marketed hard bearing cervical disc replacements. | {13} Table 4: MRI Testing | Test Description | Purpose | Methods | Medtronic's Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | MRI Characterization | To evaluate the safety and compatibility of the PRESTIGE® LP Cervical Disc System in a 3 Tesla MRI environment | n=1 (8mm x 18mm) device assemblies were tested in accordance with ASTM F2052 “Standard Test Method for Measurement of Magnetically Induced Displacement Force on Medical Devices in the Magnetic Resonance Environment,” ASTM F2182 “Standard Test Method for Measurement of Radio Frequency Induced Heating on or Near Passive Implants During Magnetic Resonance Imaging,” and ASTM F2119, “Standard Test Method for Evaluation of MR Image Artifacts from Passive Implants” | All tests were for characterization purposes and acceptance criteria were not established. | 1.) Magnetic field interactions: Implant does not present an additional risk or hazard to the patient in a 3-tesla MRI environment with regard to translational attraction, migration, or torque. 2.) MRI-related heating: Highest temperature change recorded was not considered to be physiologically consequential for a human subject. 3.) Artifact test: Worst case artifacts that appeared on MR images were localized signal voids graded as “small” in comparison to the size and shape of the device. | PMA P090029: FDA Summary of Safety and Effectiveness Data Page 14 of 79 {14} PMA P090029: FDA Summary of Safety and Effectiveness Data Page 15 of 79 # B. Laboratory Studies Two particulate injection studies were conducted in rabbit models to evaluate potential toxicity associated with debris and particulates obtained from Ti6Al4V/TiC particulates when placed in direct contact with the spinal column via epidural injection. Summary data for the studies are provided in the following table. Table 5: Animal Testing | Test Description | Purpose | Methods | Medtronic's Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | Injection Study | To evaluate the host response to PRESTIGE® LP Cervical Disc's Ti6Al4V/TiC material | Rabbits were injected in the epidural space of the spinal canal with a control solution or a mixture of solution (contrast solution mixed with 10% TiC/Ti-6Al-4V particulate injected into n=20 total rabbits) representative of wear debris. Test groups were divided into low and high doses and represented an equivalent dose of 18.9 and 57.7 million cycles of use based upon wear test data. Rabbits were terminated at 12 and 24 weeks. Local and distant tissues were harvested and examined for gross pathology (if present) and the tissue was analyzed histologically. | The test was for characterization purposes and acceptance criteria were not established. | Characterization of response to wear particles near the spine. The lungs, spleen, thymus, and lymph nodes were all observed to be unaffected by either the high or low dose. The particles generally elicited no tissue reaction or mild tissue reaction in both 12 and 24 week dose groups. | {15} | Test Description | Purpose | Methods | Medtronic’s Acceptance Criteria | Results | | --- | --- | --- | --- | --- | | Injection Study | To evaluate the potential toxicity associated with wear particulate generated from the Ti6Al4V/TiC material from which the PRESTIGE® LP Cervical Disc is manufactured | Rabbits were injected in the epidural space of the spinal canal with a control solution or a mixture of solution (contrast solution mixed with 10% TiC/Ti-6Al-4V particulate injected into n=36 total rabbits) representative of wear debris. Test groups were divided into low and high doses representing an equivalent dose of 20 and 60 million cycles of use based upon wear test data. Rabbits were terminated at 3 and 6 months. Local and distant tissues were harvested and examined for gross pathology (if present) and the tissue was analyzed histologically. | The test was for characterization purposes and acceptance criteria were not established. | Characterization of response to wear near the spine. There were no adverse tissue effects such as necrosis or excessive inflammation. | ## C. Additional Studies ### Biocompatibility Testing Per the requirements of ISO 10993-1, PRESTIGE® LP Cervical Disc device is classified as a permanent contact, tissue/bone-contacting implant. The following biocompatibility tests were undertaken on the complete device (or extract, as required): Cytotoxicity, sensitization, intracutaneous reactivity, and systemic toxicity. Data are also available for genotoxicity and implantation. All standard acceptance criteria were met. The test results support the biocompatibility of the device materials. Therefore, the Ti-6Al-4V/TiC material is considered to be safe for use in the cervical spine. ### Sterilization, Packaging and Shelf Life Validation The PRESTIGE® LP Cervical Disc is provided in a sterile package ready for use. The PRESTIGE® LP Cervical Disc is sterilized using gamma radiation at a minimum dosage of 25 kGy, at a sterilization assurance level (SAL) of 10⁻⁶. Sterilization validation according to ANSI/AAMI/ISO 11137-2:2006 was conducted to confirm that the sterility of the device is maintained through a sterile barrier. Shelf life and packaging validation studies, including packaging seal and integrity, accelerated aging, and real-time aging testing, were conducted to demonstrate the device packaging can maintain a sterile barrier with a shelf life of 8 years. PMA P090029: FDA Summary of Safety and Effectiveness Data {16} PMA P090029: FDA Summary of Safety and Effectiveness Data Page 17 of 79 # X. SUMMARY OF PRIMARY CLINICAL STUDY The applicant performed a clinical study to establish a reasonable assurance of safety and effectiveness of reconstruction of the disc at one level from C3-C7 following single-level discectomy with the PRESTIGE® LP Cervical Disc for treatment of intractable radiculopathy or myelopathy due to a single-level abnormality localized to the level of the disc space in the United States under IDE #G040086. Data from this clinical study were the basis for the PMA approval decision. A summary of the clinical study is presented below. ## A. Study Design Subjects were treated between January 13, 2005 and November 8, 2005. The database for this PMA reflected data collected through April 22, 2009 and included 280 subjects (termed "IDE Cohort") at 20 investigational sites. Fifty four additional subjects were enrolled at the same investigational sites, including: 30 subjects enrolled into a Metal Ion Cohort (MI) for which metal ion analysis was conducted based on blood draws at each follow-up time point; and, 24 Continued Access (CA) subjects. The study was a prospective, multi-center, non-randomized, unmasked, non-inferiority clinical trial conducted in the United States to compare the safety and effectiveness of the PRESTIGE® LP Cervical Disc to the standard of care (a legally marketed alternative with similar indications for use) anterior cervical discectomy and fusion (ACDF) using structural allograft and stabilization using an Atlantis® anterior cervical plate. The control group consisted of a non-randomized historical control group that received treatment with ACDF for reconstruction of the disc from C3-C7 following single-level discectomy for intractable radiculopathy and/or myelopathy in the previous IDE randomized trial of the PRESTIGE® Cervical Disc (#G010188). To adjust possible effects on clinical outcomes caused by use of historical controls, the propensity score technique was utilized. The distribution of propensity scores revealed sufficient overlapping between the two groups with respect to subject demographic and baseline characteristics. Subjects were evaluated pre-operatively, intra-operatively, immediately post-operatively and then at 6 weeks, 3 months, 6 months, 12 months, 24 months and annually thereafter. The recommended post-operative care included avoidance of overhead lifting, heavy lifting, repetitive bending, and high-impact exercise or athletic activity for 60 days postoperatively. Avoidance of prolonged (beyond 2 weeks post-op) non-steroidal anti-inflammatory drug (NSAID) use was specified in the postoperative regimen, although the use of NSAIDs was recommended for the first two weeks post-operatively. Post-operative bracing requirements were left to the discretion of the investigators and included the option for use of a soft collar as needed. The use of electrical bone growth stimulators was not recommended during the 24-month follow-up period. However, in a few cases where an electrical bone growth stimulator was utilized due to specific subject presentation, they were considered a supplemental form of therapy for spinal fusion surgery, and deemed failures included in the "Supplemental Fixation" Adverse Event category. Subjects who smoked were encouraged to discontinue smoking. {17} All adverse events (device-related or not) were monitored over the course of the study and radiographic assessments were done by an independent core laboratory. Overall success was determined by data collected during the initial 24 months of follow-up. All adverse events were independently adjudicated (for adverse event code, severity and relationship to the device and/or procedure) by a Clinical Adjudication Committee (CAC) composed of three independent spine surgeons. Note that this was a Bayesian non-inferiority study with 280 PRESTIGE® LP IDE subjects and 265 subjects in the ACDF historical control. The pre-specified non-inferiority margin was 10% and the trial was adequately powered (83% power) based on an assumption of equal success rates of 75%. The statistical plan pre-defined that the data would initially be analyzed after approximately 125 PRESTIGE® LP IDE subjects had reached the 24-month evaluation time point. At that time point, all subjects were anticipated to reach 12-month follow-up time point. The sponsor also planned to analyze the data when the entire cohort reached the 24-month time point. Due to rapid study enrollment and timing considerations, the sponsor decided not to formally perform the pre-defined interim analysis. ## 1. Clinical Inclusion and Exclusion Criteria Enrollment in the PRESTIGE® LP study was limited to subjects who met the following inclusion criteria: - Cervical degenerative disc disease defined as: intractable radiculopathy and/or myelopathy with at least one of the following items producing symptomatic nerve root and/or spinal cord compression that is documented by subject history [(e.g., pain, functional deficit, and/or neurologic deficit and imaging studies (e.g., computed tomography (CT), magnetic resonance imaging (MRI), x-rays, etc.)]: - Herniated disc; - Osteophyte formation - One level requiring surgical treatment; - C3-C4 disc to C6-C7 disc level of involvement; - Unresponsive to non-operative treatment for approximately six weeks or has the presence of progressive symptoms or signs of nerve root/spinal cord compression in the face of continued non-operative management; - No previous surgical intervention at involved level or any subsequent, planned/staged surgical procedure at the involved or adjacent level(s); - Is at least 18 years of age, inclusive, at the time of the surgery; - Preoperative Neck Disability Index score of ≥ 30; - Has a preoperative neck pain score of ≥ 20 on Preoperative Neck and Arm Pain Questionnaire; - If a female of child-bearing potential, subject is not pregnant, at the time of surgery; - Is willing to comply with the study plan and sign the Patient Informed Consent Form. Subjects were not permitted to enroll in the PRESTIGE® LP study if any of the following exclusion criteria were present: - Has a cervical spinal condition other than symptomatic cervical disc disease requiring surgical treatment at the involved level; PMA P090029: FDA Summary of Safety and Effectiveness Data Page 18 of 79 {18} - Documented or diagnosed cervical instability defined by dynamic (flexion/extension) radiographs showing sagittal plane translation > 3.5 mm or sagittal plane angulation > 20°; - More than one cervical level requiring surgical treatment; - Has a fused level adjacent to the level to be treated; - Has severe pathology of the facet joints of the involved vertebral bodies; - Previous surgical intervention at the involved level; - Has previous diagnosis of osteopenia or osteomalacia; - Has any of the following that may be associated with a diagnosis of osteoporosis (if “Yes” to any of the below risk factors, a DEXA Scan will be required to determine eligibility): - Postmenopausal non-Black female over 60 years of age and weighs less than 140 pounds. - Postmenopausal female that has sustained a non-traumatic hip, spine, or wrist fracture. - Male over the age of 70; - Male over the age of 60 that has sustained a non-traumatic hip or spine fracture; If the level of bone mineral density (BMD) is a T score of -3.5 or a T score of -2.5 with vertebral crush fracture, then the subject is excluded from the study; - Has presence of spinal metastases; - Has overt or active bacterial infection, either local or systemic; - Has severe insulin dependent diabetes; - Has chronic or acute renal failure or prior history of renal disease; - Has fever (temperature > 101°F oral) at the time of surgery; - Has a documented allergy or intolerance to stainless steel, titanium, or a titanium alloy; - Is mentally incompetent (If questionable, obtain psychiatric consult); - Is a prisoner; - Is pregnant; - Is an alcohol and/or drug abuser currently undergoing treatment for alcohol and/or drug abuse; - Has received drugs which may interfere with bone metabolism within two weeks prior to the planned date of spinal surgery (e.g. steroids or methotrexate) excluding routine perioperative anti-inflammatory drugs; - Has a history of an endocrine or metabolic disorder known to affect osteogenesis (e.g., Paget’s Disease, renal osteodystrophy, Ehlers-Danlos Syndrome, or osteogenesis imperfecta); - Has a condition that requires postoperative medications that interfere with the stability of the implant, such as steroids. (This does not include low dose aspirin for prophylactic anticoagulation), excluding routine perioperative anti-inflammatory drugs; - Has received treatment with an investigational therapy within 28 days prior to implantation surgery or such treatment is planned during the 16 weeks following implantation with the PRESTIGE® LP device. PMA P090029: FDA Summary of Safety and Effectiveness Data Page 19 of 79 {19} # 2.Follow-up Schedule Subjects were evaluated pre-operatively (within 6 months of surgery), intra-operatively, and post-operatively at 6 weeks ( $\pm$ 2 weeks), 3 months ( $\pm$ 2 weeks), 6 months ( $\pm$ one month), 12 months ( $\pm$ two months), 24 months ( $\pm$ two months), 36 months ( $\pm$ two months), 60 months ( $\pm$ two months) and 84 months ( $\pm$ two months), and annually thereafter until the last subject enrolled in the study had been seen for his or her 24-month evaluation. The following parameters were measured throughout the study: Table 6: Schedule of Study Assessments | | Pre-/Peri-Operative | | Postoperative | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | | Procedure | Pre-op | Surgery/Hospital Discharge | 6 wks | 3 mo | 6 mo | 12 mo | 24+ mo | | Preoperative Information | | | | | | | | | Confirm Patient Eligibility | X | | | | | | | | Obtain Informed Consent | X | | | | | | | | Obtain HIPAA Authorization | X | | | | | | | | Case Report Forms | | | | | | | | | Patient Enrollment | X | | | | | | | | Patient Qualification | X | | | | | | | | Preoperative Data | X | | | | | | | | Prior History Questionnaire | X | | | | | | | | Neurological Status | X | | X | X | X | X | X | | Preoperative Gait Assessment and Foraminal Compression Test | X | | | | | | | | Preoperative Patient Survey | X | | | | | | | | Preoperative Neck Disability Index | X | | | | | | | | Preoperative Neck and Arm Pain Questionnaire | X | | | | | | | | Health Status Questionnaire (SF-36) | X | | | | X | X | X | | Surgery Data | | X | | | | | | | Hospital Discharge | | X | | | | | | | Postoperative Data | | | X | X | X | X | X | | Postoperative Patient Survey | | | X | X | X | X | X | | Neck Disability Index | | | X | X | X | X | X | | Postoperative Neck and Arm Pain Questionnaire | | | X | X | X | X | X | | Postoperative Gait Assessment and Foraminal Compression Test | | | X | X | X | X | X | | Adverse Event Form (if any) | | X | X | X | X | X | X | | Outstanding (Unresolved) Adverse Event (if any) | | X | X | X | X | X | X | | Patient Disposition | | | X | X | X | X | X | | Imaging – Radiographs and Scans* | | | | | | | | | Anterior/Posterior X-ray | X | X | X | X | X | X | X | | Lateral X-ray | X | X | X | X | X | X | X | | Right/Left Lateral Bend X-rays | X | | X | X | X | X | X | | Flexion/Extension X-rays | X | | X | X | X | X | X | | CT and/or MRI | X | | | | | | | | DEXA Scan ** | X | | | | | | | * Patients who sign consent and are screened eligible, but who do not receive the PRESTIGE® LP device, were not required to have the preoperative radiographs obtained and forwarded to Medtronic. ** A DEXA Scan was only required if the patient had a risk factor that may be associated with a diagnosis of osteoporosis. PMA P090029: FDA Summary of Safety and Effectiveness Data Page 20 of 79 {20} PMA P090029: FDA Summary of Safety and Effectiveness Data Page 21 of 79 # 3. Clinical Endpoints The safety of the PRESTIGE® LP was assessed by comparison to the historical control group with respect to the nature and frequency of adverse events, secondary surgical procedures, as well as maintenance or improvement in neurological status. The effectiveness of the PRESTIGE® LP device was assessed using a composite definition of study success. The primary endpoint used for assessment of effectiveness was improvement in Neck Disability Index (NDI) pain/disability scores. In addition, several radiograph-assisted assessments were considered in evaluating both safety and effectiveness including device subsidence, functional spinal unit (FSU) height maintenance, device migration, and device breakage. According to the final IDE protocol, an individual subject in either treatment group was considered a success if the following criteria were met at 24 months : 1. An improvement (reduction) of at least 15 points from the baseline Neck Disability Index score; 2. Maintenance or improvement in neurological status; 3. Disc height (Functional Spinal Unit Height) success (FSU success) 4. No severe adverse event classified as implant-associated, surgical procedure-associated, or implant/surgical procedure-associated; and 5. No additional surgical procedure classified as "Failure" An alternative analysis of the primary endpoint analysis was also conducted without the addition of FSU height as a success criterion. Disc height success was defined as the change in FSU height being less than or equal to 2mm between a measurement obtained at the six week post-operative timepoint to FSU height at the 24 month timepoint. Secondary endpoints, measured in both treatment groups, included Radiographic Success, neck pain (VAS), arm pain (VAS), quality of life (SF-36 PCS and MCS scores), patient satisfaction, patient global perceived effort, gait assessment (Nurick's classification), and foraminal compression test. Additional measurements recorded were adjacent level stability, return to work, and doctor's perception of results. Radiographic Success for maintenance of motion is defined as >4° but <20° of angular motion based on lateral flexion/extension radiographs and no radiographic evidence of bridging trabecular bone that forms a continuous bony connection with the vertebral bodies (bridging bone). Criteria for the success of the control group was defined in a previous IDE study (G010188). Briefly, the same success criteria for the primary endpoints exist for the control group as the investigational group, with the exception that the secondary endpoint for radiographic success was defined by radiographic evidence of bone spanning the two vertebral bodies, existence of angular motion stability <4°, and no radiolucent lines covering more than 50% of the implant surface. # 4. Statistical Analysis Plan As stated previously, the study was designed as a non-inferiority trial with a margin of 10%. Bayesian statistical methods were predefined and used to determine non-inferiority and {21} superiority of the investigational device compared to the control device with respect to overall success, individual effectiveness and neurological status. A Bayesian logistic model was used to assess qualitative response outcomes, including success status, adverse event data, and additional surgical event data. A Bayesian linear model was used for assessment of surgery data, including operative time, blood loss, and hospital stay. The propensity score was used as the single covariate in the Bayesian models, mainly as a continuous independent variable, although as predefined, sensitivity analyses were also performed for the primary endpoint (overall success) and its components, in which the propensity score quantile class was used as the covariate. The study hypothesis was that the success rate of the PRESTIGE® LP group was statistically non-inferior to the success rate in the control group by a margin of $10\%$ . The primary endpoint was deemed successful, i.e., the PRESTIGE® LP is not inferior to the control, if the posterior probability that the success rate of PRESTIGE® LP group was not lower than control group by more than $10\%$ was greater than $95\%$ . If non-inferiority was demonstrated, analyses were also defined in the statistical plan to determine whether the investigational group had statistically superior outcomes as compared to the control group. # B.Accountability of PMA Cohort The subject accountability data are summarized in Table 7. Please note that Continued Access Cohort (CA) and the Metal Ion Cohort (MI) were enrolled separately from the IDE Cohort at the same study sites. Safety and effectiveness data were collected for the IDE, Safety $(\mathrm{IDE} + \mathrm{CA} + \mathrm{MI})$ , and ACDF Control Cohorts while the statistical analyses were performed with the IDE Cohort in comparison to the control group. Table 7: Subject Accountability | Number of Subjects: | 12 Months(±2 Months) | | | 24 Months(±2 Months) | | | | --- | --- | --- | --- | --- | --- | --- | | | PRESTIGE®LP IDECohort | ACDFControl | PRESTIGE®LP SafetyCohort | PRESTIGE®LP IDECohort | ACDFControl | PRESTIGE®LP SafetyCohort | | Enrolled | 280 | 265 | 333 | 280 | 265 | 333 | | Theoretical FU | 280 | 265 | 333 | 280 | 265 | 333 | | Cumulative Deaths2 | 0 | 2 | 0 | 0 | 2 | 0 | | Subjects Evaluated Early3 | 0 | 0 | 0 | 0 | 0 | 0 | | Subjects Not Yet Overdue | 0 | 0 | 0 | 0 | 0 | 0 | | Expected4 | 280 | 263 | 333 | 280 | 263 | 333 | | Evaluable for Overall Success(% of Total Expected) | 274(97.9%) | 223(84.8%) | 326(97.9%) | 271(96.8%) | 220(83.7%) | 322(96.7%) | | Evaluable for Overall Success, InWindow | 271(96.8%) | 206(78.3%) | 321(96.4%) | 262(93.6%) | 201(76.4%) | 309(92.8%) | PMA P090029: FDA Summary of Safety and Effectiveness Data {22} In addition to the study subjects described above, nineteen (19) subjects were consented but declined participation in the study prior to receiving the assigned treatment. The demographic and preoperative characteristics of the subjects who declined to participate in this study were comparable to the subjects included in this study. A summary of accountability regarding data for specific study assessments at 24 months is provided in Table 8 below. Table 8: 24-Month Data Accounting For Specific Study Assessments | Variables | PRESTIGE® LP IDE Cohort (N=280) | ACDF Control (N=265) | PRESTIGE® LP Safety Cohort (N=333) | | --- | --- | --- | --- | | NDI | 270 (96.4%) | 219 (82.6%) | 322 (96.7%) | | Neurological | 270 (96.4%) | 220 (83.0%) | 321 (96.4%) | | SF-36 PCS | 265 (94.6%) | 218 (82.3%) | 317 (95.2%) | | SF-36 MCS | 265 (94.6%) | 218 (82.3%) | 317 (95.2%) | | Neck Pain | 270 (96.4%) | 220 (83.0%) | 322 (96.7%) | | Arm Pain | 268 (95.7%) | 220 (83.0%) | 320 (96.1%) | | Patient Perceived Effect | 270 (96.4%) | 219 (82.6%) | 323 (97.0%) | | Doctor’s Perception | 271 (96.8%) | 220 (83.0%) | 323 (97.0%) | | Patient Satisfaction | 270 (96.4%) | 219 (82.6%) | 323 (97.0%) | | Gait | 270 (96.4%) | 220 (83.0%) | 322 (96.7%) | | Foraminal Compression | 270 (96.4%) | 220 (83.0%) | 322 (96.7%) | | Radiographic Assessment | 264 (94.3%) | - | 316 (94.9%) | ## C. Study Population Demographics and Baseline Parameters Table 9 presents the summary statistics for demographic and baseline characteristics for the PRESTIGE® LP IDE Cohort, the ACDF Control, and PRESTIGE® LP Safety Cohort. The demographics of the study population are consistent with the demographics reported for prior cervical artificial disc studies conducted in the U.S. The investigational and control treatment groups were very similar demographically, and there were no statistically significant differences (p<0.05) for any of the variables except for the use of tobacco and race. Current tobacco use was higher in the control group (34.7% versus 26.4%) as compared to the IDE Cohort. However, tobacco use was established through use of patient questionnaires which utilized a binary response (i.e., yes or no), and quantification of the extent or history of tobacco use was not established. Therefore, it is not possible to definitively ascertain whether there were any substantial confounding effects from tobacco use on subject outcomes. Regarding race differences among cohorts, there was a higher percentage of Caucasian subjects in the IDE Cohort compared to the control group (96.8% versus 91.7%). PMA P090029: FDA Summary of Safety and Effectiveness Data Page 23 of 79 {23} Table 9: Study Population Demographics and Baseline Characteristics | Variables | PRESTIGE® LP IDE Cohort (N=280) | ACDF Control (N=265) | PRESTIGE® LP Safety Cohort (N=333) | p-value (IDE vs. Control) | | --- | --- | --- | --- | --- | | Age (years) | 44.5 ± 8.8 Range: 23 - 78 | 43.9 ± 8.8 Range: 22 - 73 | 43.8 ± 9.0 Range: 23 - 78 | 0.369 | | Height (inches) | 67.7 ± 4.1 Range: 60.0 - 77.0 | 67.5 ± 4.2 Range: 58.0 - 80.0 | 67.7 ± 4.0 Range: 60.0 - 77.0 | 0.622 | | Weight (lbs.) | 186.9 ± 45.0 Range: 100.0 - 340.0 | 184.7 ± 41.5 Range: 98.0 - 328.0 | 187.3 ± 45.2 Range: 100.0 - 340.0 | 0.567 | | BMI (kg/m²) | 28.5 ± 5.6 Range: 17.2 - 48.2 | 28.3 ± 5.1 Range: 19.0 - 53.6 | 28.5 ± 5.6 Range: 17.2 - 48.2 | 0.722 | | Sex | | | | | | Male (%) | 129 (46.1%) | 122 (46.0%) | 155 (46.5%) | 1.000 | | Female (%) | 151 (53.9%) | 143 (54.0%) | 178 (53.5%) | | | Race | | | | | | Caucasian | 271 (96.8%) | 243 (91.7%) | 320 (96.1%) | | | Black | 7 (2.5%) | 13 (4.9%) | 10 (3.0%) | | | Asian | 0 (0.0%) | 2 (0.8%) | 1 (0.3%) | 0.043 | | Hispanic | 1 (0.4%) | 6 (2.3%) | 1 (0.3%) | | | Other | 1 (0.4%) | 1 (0.4%) | 1 (0.3%) | | | Marital Status | | | | | | Single | 40 (14.3%) | 32 (12.1%) | 47 (14.1%) | | | Married | 189 (67.5%) | 204 (77.0%) | 224 (67.3%) | | | Divorced | 42 (15.0%) | 24 (9.1%) | 51 (15.3%) | 0.096 | | Separated | 7 (2.5%) | 3 (1.1%) | 8 (2.4%) | | | Widowed | 2 (0.7%) | 2 (0.8%) | 3 (0.9%) | | | Education Level | | | | | | < High School | 15 (5.4%) | 14 (5.3%) | 17 (5.1%) | | | High School | 57 (20.5%) | 77 (29.2%) | 78 (23.6%) | 0.062 | | > High School | 206 (74.1%) | 173 (65.5%) | 236 (71.3%) | | | Previous Neck Surgery | | | | | | Yes | 3 (1.1%) | 2 (0.8%) | 3 (0.9%) | 1.000 | | No | 277 (98.9%) | 263 (99.2%) | 330 (99.1%) | | | Preoperative Medication use | | | | | | Non-Narcotics | 208/280 (74.3%) | 187/263 (71.1%) | 246/333 (73.9%) | 0.441 | | Weak Narcotics | 133/279 (47.7%) | 127/263 (48.3%) | 152/332 (45.8%) | 0.931 | | Strong Narcotics | 62/279 (22.2%) | 58/264 (22.0%) | 68/332 (20.5%) | 1.000 | | Muscle Relaxants | 100/279 (35.8%) | 114/264 (43.2%) | 123/332 (37.0%) | 0.095 | PMA P090029: FDA Summary of Safety and Effectiveness Data Page 24 of 79 {24} | Variables | PRESTIGE® LP IDE Cohort (N=280) | ACDF Control (N=265) | PRESTIGE® LP Safety Cohort (N=333) | p-value (IDE vs. Control) | | --- | --- | --- | --- | --- | | Preoperative Pain Status^{5} | | | | | | Arm and Neck Pain | 255 (91.1%) | 238 (90.2%) | 299 (89.8%) | 0.769 | | Arm Pain Only | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) | | | Neck Pain Only | 25 (8.9%) | 26 (9.8%) | 34 (10.2%) | | | Worker’s Compensation | 32/280 (11.4%) | 35/365 (13.2%) | 54/333 (16.2%) | 0.602 | | Unresolved Spinal Litigation | 34/280 (12.1%) | 32/265 (12.1%) | 61/333 (18.3%) | 1.000 | | Current Tobacco Use | 74/280 (26.4%) | 92/265 (34.7%) | 94/333 (28.2%) | 0.041 | | Current Alcohol Use | 150/280 (53.6%) | 141/265 (53.2%) | 172/333 (51.7%) | 1.000 | | Preoperative Work Status | 188/280 (67.1%) | 166/265 (62.6%) | 217/333 (65.2%) | 0.282 | | Duration of Symptoms | | | | | | < 6 wks. | 22 (7.9%) | 15 (5.7%) | 24 (7.2%) | 0.494 | | 6 wks. – 6 mos. | 85 (30.4%) | 89 (33.6%) | 97 (29.1%) | | | > 6 mos. | 173 (61.8%) | 161 (60.8%) | 212 (63.7%) | | The mean baseline pre-operative assessments for the PRESTIGE® LP IDE Cohort, Control Group, and PRESTIGE Safety Cohort are presented in Table 10. There were no statistical differences between the PRESTIGE® LP IDE Cohort and Control for NDI, SF-36 PCS, SF-36 MCS, neck pain, and arm pain. There were statistically significant differences in baseline motor neurologic status (38.2% - PRESTIGE® LP IDE Cohort; 59.5% - Control) and mean cervical range of motion (5.67° - PRESTIGE® LP IDE Cohort; 7.87° - Control). However, after propensity score adjustments, the variables appeared balanced between groups. Thus, differences in baseline symptoms were adjusted for in the analysis and are therefore unlikely to have led to significant bias in the reported results. PMA P090029: FDA Summary of Safety and Effectiveness Data Page 25 of 79 {25} Table 10: Preoperative Evaluation of Clinical Endpoints | Variables | PRESTIGE® LP IDE Cohort (N=280) | ACDF Control (N=265) | PRESTIGE® LP Safety Cohort (N=333) | p-value (IDE Cohort vs ACDF Control) | | --- | --- | --- | --- | --- | | NDI | 55.5 ± 14.7 Range: 30.0 – 98.0 | 56.4 ± 15.9 Range: 26.0 – 100.0 | 56.6 ± 15.0 Range: 30.0 – 98.0 | 0.498 | | SF-36 PCS | 32.2 ± 7.4 Range: 14.3 – 57.9 | 32.0 ± 7.5 Range: 7.9 – 56.0 | 32.3 ± 7.1 Range: 14.3 – 57.9 | 0.777 | | SF-36 MCS | 44.5 ± 11.5 Range: 16.5 – 68.3 | 42.7 ± 12.4 Range: 14.1 – 70.8 | 43.8 ± 11.9 Range: 16.5 – 68.3 | 0.079 | | Neck Pain Score | 67.0 ± 20.8 Range: 20.0 – 100.0 | 69.3 ± 21.5 Range: 20.0 – 100.0 | 68.0 ± 20.8 Range: 20.0 – 100.0 | 0.191 | | Arm Pain Score | 59.6 ± 26.3 Range: 0.0 – 100.0 | 62.4 ± 28.5 Range: 0.0 – 100.0 | 59.0 ± 27.1 Range: 0.0 – 100.0 | 0.236 | | Neurological Status (normal) | | | | | | • Motor | 107/280 (38.2%) | 157/264 (59.5%) | 135/333 (40.5%) | < 0.001 | | • Sensory | 117/280 (41.8%) | 134/264 (50.8%) | 147/333 (44.1%) | 0.039 | | • Reflexes | 186/280 (66.4%) | 161/264 (61.0%) | 200/333 (60.1%) | 0.212 | | • Overall^{6} | 64/280 (22.9%) | 79/264 (29.9%) | 73/333 (21.9%) | 0.065 | | Baseline ROM angulation (°) | 5.67 ± 3.69 Range: 0.27 – 18.10 | 7.87 ± 4.32 Range: 0.74 – 21.34 | 5.88 ± 3.78 Range: 0.27 – 19.47 | < 0.001 | | Baseline ROM translation (mm) | N/A | 0.26 ± 0.25 Range: 0.00 – 1.64 | N/A | N/A | ## D. Safety and Effectiveness Results ### 1. Safety Results The analysis of safety was based on the as-treated cohort of 598 total subjects with surgery (333 PRESTIGE® LP “Safety” subjects consisting of 280 PRESTIGE® LP IDE Cohort subjects, as well as 54 subjects from the Continued Access(CA) and Metal Ion(MI) Cohorts; and 265 ACDF control subjects). This was a non-randomized study and the ACDF group was a historical control. ### Adverse events that occurred in the PMA clinical study A summary of the total number of adverse events is shown in Table 11. Adverse events were classified by the independent Clinical Adjudication Committee (CAC) for severity and relationship to the device and/or surgical procedure. The overall adverse event rate was higher for subjects treated with the PRESTIGE® LP device (IDE Cohort, 91.8%; Safety Cohort, 91.9%) compared to the Control (82.6%) through 24 months. The adverse event rate between the PRESTIGE® LP IDE Cohort and the Control was statistically different with the 95% BCI for the difference of adverse events rates between the PRESTIGE® LP IDE Cohort and the ACDF Control Cohort being (4.1%, 16.2%), excluding 0. Although the rate of PMA P090029: FDA Summary of Safety and Effectiveness Data {26} PRESTIGE® LP IDE subjects having at least one adverse event was statistically higher than the control group rate, the difference in adverse event rates was not considered to be clinically meaningful and this finding may be attributable to the higher follow-up rates (and potentially, higher reporting of events) for investigational subjects as compared to the ACDF control subjects. Specifically, note that the 24-month follow-up rates are 97.1% and 84.0% respectively for the PRESTIGE® LP IDE Cohort and ACDF Control Cohort. Table 11: Summary of Adverse Events Up to the 24-Month Time Interval | Adverse Event Type | Measure | PRESTIGE® LP IDE Cohort (N=280) | ACDF Control (N=265) | PRESTIGE® LP Safety Cohort (N=333) | Posterior Mean and 95% BCI^{8} of the Difference of Event Rate between IDE Cohort and ACDF Control^{9} | | --- | --- | --- | --- | --- | --- | | All Adverse Events (AEs) | Subjects (%) | 257 (91.8%) | 219 (82.6%) | 306 (91.9%) | 10.2% (4.1%, 16.2%) | | | Events (Events/Subject) | 1559 (5.57) | 1198 (4.52) | 1863 (5.59) | | | Device or Device/Surgical Procedure Related AEs | Subjects (%) | 34 (12.1%) | 41 (15.5%) | 44 (13.2%) | -2.9% (-9.2%, 3.3%) | | | Events (Events/Subject) | 61 (0.22) | 60 (0.23) | 76 (0.23) | | | Surgical Procedure Related AEs Only | Subjects (%) | 72 (25.7%) | 71 (26.8%) | 78 (23.4%) | -0.5% (-8.6%, 7.4%) | | | Events (Events/Subject) | 132 (0.47) | 121 (0.46) | 140 (0.42) | | | Severe AEs (Grade 3 or 4) | Subjects (%) | 133 (47.5%) | 98 (37.0%) | 163 (48.9%) | 13.3% (3.5%, 21.8%) | | | Events (Events/Subject) | 433 (1.55) | 267 (1.01) | 518 (1.56) | | | Severe Device or Device/Procedure-Related AEs (Grade 3 or 4) | Subjects (%) | 14 (5.0%) | 13 (4.9%) | 16 (4.8%) | 0.7% (-3.0%, 4.6%) | | | Events (Events/Subject) | 33 (0.12) | 22 (0.08) | 40 (0.12) | | ## Adverse Events by Level of Treatment Table 12 provides summary data on the number of adverse events in each treatment group by treatment level, including post-hoc statistical analysis and comparison between the PRESTIGE® LP IDE Cohort and the ACDF control group through the 24-month time point using Frequentist methods. The percentage of subjects with adverse events was not statistically different between the two groups for all levels except for C5-C6; however, this difference was not clinically meaningful. PMA P090029: FDA Summary of Safety and Effectiveness Data Page 27 of 79 {27} Table 12: Summary of Total Adverse Events by Level Treated through Month 24- IDE and Safety Population | Treatment Level | PRESTIGE® LP IDE Cohort (N=280) | ACDF Control (N=265) | PRESTIGE® LP Safety Cohort (N=333) | Point Estimate and 95% Confidence Interval^{10} of Difference of Adverse Rate between IDE Cohort and ACDF Control Cohort | | --- | --- | --- | --- | --- | | C3-C4 | 4/4 (100%) | 9/10 (90.0%) | 4/4 (100.0%) | 10.0% (-19.9%, 39.9%) | | C4-C5 | 20/21 (95.2%) | 12/15 (80.0%) | 27/28 (96.4%) | 15.2% (-5.6%, 36.1%) | | C5-C6 | 135/147 (91.8%) | 124/149 (83.2%) | 163/178 (91.6%) | 8.6% (1.1%, 16.2%) | | C6-C7 | 98/108 (90.7%) | 74/91 (81.3%) | 112/123 (91.1%) | 9.4% (-0.1%, 19.0%) | ## All Adverse Events The adverse events reported in the PMA from all 598 total subjects (333 PRESTIGE® LP Safety Cohort subjects, including the 280 PRESTIGE® LP IDE Cohort subject, and 265 ACDF Control subjects) are shown in Table 13. This table includes adverse events from all subjects to establish the safety profile of the device for the primary study endpoint (24 months). Adverse events are listed in alphabetical order according to adverse event categories. Definitions of the adverse event categories are provided in Table 14. Table 15 is presented in a similar fashion as Table 13 (using the categories as defined in Table 14). Adverse event rates are based on the number of subjects having at least one occurrence of an adverse event, divided by the number of subjects in that treatment group. Events per subject in Table 11 are based on the number of adverse events, divided by the total number of subjects in each cohort. Subjects experiencing adverse events in more than one category are represented in each category in which they experienced an adverse event. The most commonly reported categories of adverse events through 24 months were Neck and/or Arm Pain (in 55.3% of PRESTIGE® LP Safety Cohort subjects, 51.4% of PRESTIGE® LP IDE Cohort Subjects, and 46.8% of ACDF Control subjects), Other Pain (in 52.6% of PRESTIGE® LP Safety Cohort subjects, 52.1% of PRESTIGE® LP IDE Cohort Subjects, and 49.8% of ACDF Control subjects), Neurological (in 48.6% of PRESTIGE® LP Safety Cohort and IDE Cohort subjects and 40.8% of ACDF Control subjects), Other (in 33.0% of PRESTIGE® LP Safety Cohort subjects, 33.2% of PRESTIGE® LP IDE Cohort Subjects, and 30.6% of ACDF Control subjects), Spinal Event (in 31.8% of PRESTIGE® LP Safety Cohort subjects, 29.6% of PRESTIGE® LP IDE Cohort Subjects, and 20.8% of ACDF Control subjects), Trauma (in 20.7% of PRESTIGE® LP Safety Cohort subjects, 21.8% of PRESTIGE® LP IDE Cohort Subjects, and 13.2% of ACDF Control subjects), Gastrointestinal (in 12.9% of PRESTIGE® LP Safety Cohort subjects, 12.5% of PRESTIGE® LP IDE Cohort Subjects, and 14.3% of ACDF Control subjects), and Infection (in 12.0% of PRESTIGE® LP Safety Cohort subjects, 12.1% of PRESTIGE® LP IDE Cohort Subjects, and 10.2% of ACDF Control subjects). The non-union rate in ACDF control subjects was 10.9%. PMA P090029: FDA Summary of Safety and Effectiveness Data Page 28 of 79 {28} There were a total of three deaths in the investigational group and five deaths in the control group, of which two deaths occurred in the control group prior to 24 months (at the 12-month time point) and none in the investigational group prior to 24 months. Deaths were evaluated based upon available information and none of the deaths were believed to be in any way related to the study treatment. PMA P090029: FDA Summary of Safety and Effectiveness Data Page 29 of 79 {29} Table 13: Adverse Events in Pivotal Study Through 24 Months ${}^{{11},{12}}$ | | Surgery | | | Postoperative (1 day - <4 Weeks) | | | 6 Weeks (≥4 Wks - <9 Weeks) | | | 3 Months (≥9 Wks - <5 Months) | | | 6 Months (≥5 Mos - <9 Months) | | | 12 Months (≥9 Mos - <19 Months) | | | 24 Months (≥19 Mos - <30 Months) | | | Total (Up to 24 Month) # of Subjects Reporting & Total adverse events | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | Adverse Events | PRESTIGE® LP IDE Cohort | ACDF Control13 | PRESTIGE® LP Safety Cohort | ACDF Control | PRESTIGE® LP Safety Cohort | ACDF Control | PRESTIGE® LP Safety Cohort | ACDF Control | PRESTIGE® LP Safety Cohort | ACDF Control | PRESTIGE® LP Safety Cohort | ACDF Control | PRESTIGE® LP Safety Cohort | ACDF Control | PRESTIGE® LP Safety Cohort | ACDF Control | PRESTIGE® LP Safety Cohort | ACDF Control | PRESTIGE® LP Safety Cohort | ACDF Control | PRESTIGE® LP Safety Cohort | Total # Events | Total (Up to 24 Month) # of Subjects Reporting & Total adverse events | | | Anatomical / Technical Difficulty | 2 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 (0.7) 2 | 0 (0.0) 0 | 2 (0.6) 2 | | | Cancer | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 3 | 0 | 3 | 0 | 1 | 2 | 3 (1.1) 5 | 2 (0.8) 2 | 5 (1.5) 7 | | Cardiac Disorders | 0 | 0 | 0 | 2 | 2 | 2 | 2 | 1 | 3 | 0 | 2 | 0 | 3 | 3 | 3 | 4 | 3 | 5 | 10 | 9 | 11 | 16 (5.7) 21 | 18 (6.8) 20 | 19 (5.7) 24 | | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 (0.0) 0 | 0 (0.0) 0 | 0 (0.0) 0 | | Dysphagia / Dysphonia | 1 | 4 | 1 | 16 | 11 | 17 | 4 | 4 | 6 | 5 | 3 | 5 | 5 | 0 | 5 | 0 | 1 | 1 | 2 | 0 | 3 | 26 (9.3) 33 | 22 (8.3) 23 | 30 (9.0) 38 | | Gastrointestinal | 2 | 7 | 2 | 8 | 7 | 8 | 1 | 3 | 2 | 4 | 4 | 7 | 3 | 2 | 7 | 20 | 21 | 22 | 17 | 24 | 20 | 35 (12.5) 55 | 38 (14.3) 68 | 43 (12.9) 68 | | Heterotopic Ossification | 0 | 0 | 0 | 2 | 1 | 2 | 6 | 4 | 6 | 1 | 2 | 1 | 4 | 1 | 5 | 7 | 2 | 9 | 11 | 11 | 12 | 27 (9.6) 31 | 15 (5.7) 21 | 31 (9.3) 35 | | Implant Events | 6 | 0 | 6 | 1 | 1 | 1 | 2 | 1 | 3 | 3 | 0 | 3 | 1 | 0 | 3 | 0 | 2 | 1 | 4 | 1 | 5 | 16 (5.7) 17 | 5 (1.9) 5 | 21 (6.3) 22 | | Infection | 1 | 2 | 1 | 5 | 3 | 5 | 6 | 5 | 7 | 6 | 2 | 9 | 11 | 1 | 12 | 16 | 10 | 16 | 12 | 14 | 13 | 34 (12.1) 57 | 27 (10.2) 37 | 40 (12.0) 63 | | Neck and / or Arm Pain | 3 | 1 | 4 | 31 | 16 | 35 | 43 | 19 | 57 | 57 | 49 | 77 | 37 | 40 | 50 | 68 | 50 | 84 | 36 | 38 | 46 | 144 (51.4) 275 | 124 (46.8) 213 | 184 (55.3) 353 | | Neurological | 2 | 6 | 2 | 18 | 21 | 20 | 34 | 19 | 42 | 47 | 35 | 55 | 31 | 16 | 39 | 73 | 60 | 88 | 37 | 60 | 43 | 136 (48.6) 242 | 108 (40.8) 217 | 162 (48.6) 289 | | Non-Union | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 3 | 0 | 0 | 8 | 0 | 0 | 8 | 0 | 0 | 10 | 0 | 0 (0.0) 0 | 29 (10.9) 30 | 0 (0.0) 0 | | Other | 5 | 3 | 8 | 19 | 14 | 22 | 12 | 13 | 14 | 24 | 16 | 28 | 29 | 9 | 38 | 55 | 21 | 58 | 33 | 57 | 39 | 93 (33.2) 177 | 81 (30.6) 133 | 110 (33.0) 207 | | Other Pain14 | 3 | 6 | 3 | 22 | 19 | 23 | 32 | 11 | 39 | 49 | 45 | 65 | 57 | 30 | 69 | 65 | 57 | 71 | 50 | 63 | 58 | 146 (52.1) 278 | 132 (49.8) 231 | 175 (52.6) 328 | | Respiratory | 0 | 0 | 0 | 7 | 4 | 7 | 0 | 4 | 1 | 1 | 1 | 1 | 10 | 5 | 10 | 3 | 1 | 6 | 13 | 8 | 14 | 24 (8.6) 34 | 17 (6.4) 23 | 27 (8.1) 39 | | Spinal Event | 0 | 0 | 0 | 19 | 8 | 22 | 22 | 6 | 34 | 20 | 25 | 25 | 26 | 15 | 31 | 44 | 20 | 53 | 41 | 29 | 47 | 83 (29.6) 172 | 55 (20.8) 103 | 106 (31.8) 212 | | Trauma | 0 | 0 | 0 | 6 | 2 | 7 | 5 | 4 | 6 | 12 | 12 | 13 | 11 | 5 | 12 | 19 | 9 | 20 | 18 | 12 | 21 | 61 (21.8) 71 | 35 (13.2) 44 | 69 (20.7) 79 | | Urogenital | 1 | 0 | 1 | 1 | 0 | 1 | 2 | 0 | 2 | 1 | 1 | 1 | 9 | 3 | 9 | 12 | 5 | 13 | 16 | 2 | 20 | 26 (9.3) 42 | 9 (3.4) 11 | 31 (9.3) 47 | | Vascular | 3 | 1 | 4 | 1 | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 0 | 2 | 1 | 2 | 2 | 1 | 2 | 4 | 0 | 4 | 12 (4.3) 13 | 4 (1.5) 4 | 13 (3.9) 14 | | Wound (Non-Infectious) | 0 | 2 | 1 | 14 | 4 | 15 | 3 | 2 | 3 | 4 | 2 | 4 | 4 | 1 | 4 | 5 | 2 | 5 | 4 | 0 | 4 | 25 (8.9) 34 | 13 (4.9) 13 | 27 (8.1) 36 | | Any Adverse Event | | | | | | | | | | | | | | | | | | | | | | | | | 11 Based on 24-month cohort. 12 Some adverse events may lead to additional surgeries or interventions. Refer to Table 9 for more information. 13 Control=Single-level anterior interbody fusion procedure with allograft and plate stabilization. Non-randomized control arm from IDE study of PRESTIGE® Cervical Disc. Back and/or lower extremity (LE) pain adverse events (AEs) and Headache AE's were classified as "Other Pain" AEs for the PRESTIGE® LP IDE study. PMA P090029: FDA Summary of Safety and Effectiveness Data {30} Table 14: Adverse Event Categories | Adverse Event Category | Definition | | --- | --- | | Anatomical/Technical Difficulty – Cervical Study Surgery | Anatomical or technical difficulty encountered during the original implantation of the PRESTIGE® device or control treatment device | | Anatomical/Technical Difficulty – Cervical Non-Study Surgery | Anatomical or technical difficulty encountered during an additional surgery involving the cervical region, but did not involve the PRESTIGE® device or original control treatment device | | Anatomical/Technical Difficulty Non-Cervical | Technical problem encountered during an additional surgery that involved a region other than the cervical spine | | Cancer | A malignancy or malignant tumor/neoplasm | | Cardiac Disorders | Any condition of the heart | | Death | Termination of life due to any cause | | Dysphagia | Difficulty in swallowing | | Dysphonia | Difficulty in speaking | | Gastrointestinal | Any condition pertaining to the stomach and intestines | | Heterotopic Ossification - Cervical | Event involving heterotopic ossification at any region of the cervical spine | | Heterotopic Ossification - Non-Cervical | Event involving heterotopic ossification at any region of the spine that is not cervical or any other region of the body. | | Implant Events - Malpositioning | Poor or inappropriate placement of the implant | | Implant Events - Displacement | Incomplete or partial dislocation of the implant | | Implant Events - Loosening | Wear around the implant and/or loosening of the implant surface | | Implant Events - Breakage | Breakage of any implant or implant component | | Implant Events - Other | Event that is implant-related, but does not meet the definition of malpositioned implant, implant displacement, implant loosening, or implant breaking | | Infection - Superficial | An infection near the surface of the surgical incision | | Infection - Deep | An infection below the fascia at the surgical incision | | Infection - Other Wound | Infection occurring in other surgical wound not involving the study | | Infection - Hematoma | Swelling or mass of blood that has become infected | | Infection - CSF Leak | Infection resulting from the leakage of CSF | | Infection - Systemic | Infection pertaining to the whole body | | Infection - Urinary Tract | Infection of any part of the urinary system | | Infection - Other | Any infection not listed above | | Pain - Neck | Pain (including stiffness, strain, tightness) in the neck | | Pain - Upper Extremities | Pain (including stiffness, strain, tightness) in the shoulder, arm, wrist or hand | | Pain - Neck and Upper Extremities | Pain (including stiffness, strain, tightness) in the neck and shoulder, arm, wrist, or hand | | Pain - Other | Pain (including stiffness, strain, tightness) in an area that is not of cervical spine etiology (e.g., abdominal pain of unknown etiology, headache, flank pain, bursitis). | | Other | Event not associated with any other categories (e.g., weight loss, tinnitus, substance abuse, insomnia). | | Respiratory | Ailments or symptoms associated with respiration or the respiratory system | | Spinal Event – Cervical Study Surgery | Event involving the treated level of cervical spine | | Spinal Event – Cervical Non-Study Surgery | Event involving one or more cervical spine level(s), with the exception of the treated level | | Spinal Event - Non-Cervical | Event involving one or more spine levels other than cervical spine | PMA P090029: FDA Summary of Safety and Effectiveness Data Page 31 of 79 {31} | Adverse Event Category | Definition | | --- | --- | | Trauma | Physical injury caused by a physical force or traumatic event (e.g. motor vehicle accident, fall, etc.) | | Urogenital | Any condition of, relating to, affecting, treating, or being the organs or functions of excretion and reproduction | | Vascular – injury (intraoperative) | Injury to a vascular structure that is sustained during the course of the operative procedure | | Vascular – Vertebral artery | Injury to vertebral artery occurring at any time | | Vascular - Other | Disorder or condition in which the vascular system is affected | | Wound (Non-Infectious) | Any issue of surgical incision, such as hematoma, excluding infection | Bayesian analyses were conducted on all adverse events using non-informative priors. The results are presented in Table 15 with 95% Bayesian Credible Intervals (BCI) for the difference in adverse event rates (PRESTIGE® LP IDE – ACDF). BCIs that exclude zero indicate statistical differences in the adverse event rates between the PRESTIGE® LP IDE cohort and the ACDF Control group while the BCIs that include zero fail to conclude that this is a statistical difference in the adverse event rates between the two groups. Based on the BCIs, statistical differences were noted between groups for the adverse event rates in the following categories: heterotopic ossification, implant events, neurological, non-union, spinal events, trauma, urogenital, vascular, and wound (non-infectious). All are statistically higher for the PRESTIGE® LP IDE Cohort except for non-union which was statistically higher for the control group. PMA P090029: FDA Summary of Safety and Effectiveness Data Page 32 of 79 {32} Table 15: Bayesian Comparison of Posterior Probabilities of Adverse Events | Adverse Event | Subjects Experiencing Adverse Events (%) | | | Posterior Mean and 95% HPD of Adverse Event Rate | | Posterior Mean and 95% BCI15 of Difference of Adverse Event Rate between LP IDE Cohort and ACDF Control | | --- | --- | --- | --- | --- | --- | --- | | | IDE Cohort | ACDF Control | Safety Cohort | IDE Cohort | ACDF Control | IDE - ACDF | | Anatomical / Technical Difficulty | 2 (0.7%) | 0 (0.0%) | 2 (0.6%) | 0.5% (0.0%, 1.4%) | 0.0% (0.0%, 0.1%) | 0.5% (0.0%, 1.4%) | | Cancer | 3 (1.1%) | 2 (0.8%) | 5 (1.5%) | 1.0 (0.1%, 2.3%) | 0.6% (0.0%, 1.6%) | 0.4% (-1.2%, 2.0%) | | Cardiac Disorders | 16 (5.7%) | 18 (6.8%) | 19 (5.7%) | 5.4% (2.8%, 8.2%) | 7.0% (4.0%, 10.4%) | -1.6% (-6.0%, 2.9%) | | Dysphagia / Dysphonia | 26 (9.3%) | 22 (8.3%) | 30 (9.0%) | 9.3% (5.9%, 12.9%) | 8.2% (4.8%, 11.6%) | 1.0% (-4.2%, 6.1%) | | Gastrointestinal | 35 (12.5%) | 38 (14.3%) | 43 (12.9%) | 12.9% (9.0%, 17.3%) | 13.7% (9.3%, 17.9%) | -0.8% (-7.2%, 5.1%) | | Heterotopic Ossification | 27 (9.6%) | 15 (5.7%) | 31 (9.3%) | 10.2% (6.7%, 14.0%) | 5.0% (2.5%, 7.7%) | 5.2% (0.5%, 10.1%)* | | Implant Events | 16 (5.7%) | 5 (1.9%) | 21 (6.3%) | 5.7% (3.0%, 8.7%) | 1.8% (0.4%, 3.4%) | 3.9% (0.6%, 7.4%)* | | Infection | 34 (12.1%) | 27 (10.2%) | 40 (12.0%) | 12.0% (8.2%, 16.1%) | 10.3% (6.6%, 14.2%) | 1.7% (-3.8%, 7.5%) | | Neck and / or Arm Pain | 144 (51.4%) | 124 (46.8%) | 184 (55.3%) | 51.9% (45.9%, 57.9%) | 46.2% (39.7%, 52.3%) | 5.7% (-3.3%, 15.0%) | | Neurological | 136 (48.6%) | 108 (40.8%) | 162 (48.6%) | 49.4% (43.2%, 55.6%) | 39.8% (33.7%, 46.1%) | 9.6% (0.6%, 18.9%)* | | Non-Union | 0 (0.0%) | 29 (10.9%) | 0 (0.0%) | 0.0% | 11.4% (7.3%, 15.4%) | -11.3% (-15.4%, -7.3%)* | | Other | 93 (33.2%) | 81 (30.6%) | 110 (33.0%) | 33.6% (27.9%, 39.5%) | 30.1% (24.4%, 36.0%) | 3.5% (-4.9%, 12.1%) | | Other Pain | 146 (52.1%) | 132 (49.8%) | 175 (52.6%) | 51.3% (45.3%, 57.4%) | 50.7% (44.2%, 56.8%) | 0.6% (-8.5%, 9.7%) | | Respiratory | 24 (8.6%) | 17 (6.4%) | 27 (8.1%) | 8.3% (4.9%, 11.7%) | 6.5% (3.6%, 9.7%) | 1.9% (-2.9%, 6.7%) | | Spinal Event | 83 (29.6%) | 55 (20.8%) | 106 (31.8%) | 31.4% (25.7%, 37.2%) | 19.0% (13.8%, 23.8%) | 12.4% (4.5%, 20.3%)* | | Trauma | 61 (21.8%) | 35 (13.2%) | 69 (20.7%) | 21.2% (16.4%, 26.3%) | 13.5% (9.4%, 17.9%) | 7.6% (0.7%, 14.4%)* | | Urogenital | 26 (9.3%) | 9 (3.4%) | 31 (9.3%) | 8… --- **Source:** [https://fda.innolitics.com/device/P090029](https://fda.innolitics.com/device/P090029) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. 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