A Comparison of Stryker's Tritanium Posterior Lumbar Cage and PEEK Implant on Spinal Fusion in Patients With Degenerative Disc Disease
Phase: NA
Conditions: Degenerative Disc Disease, Degenerative Scoliosis
Sponsor: Riverside Medical Center

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A Comparison of Stryker’s Tritanium® Posterior Lumbar Cage and PEEK Implant 
on Spinal Fusion in Patients with Degenerative Disc Disease 
 
 
 
Protocol Identifying Number: RMC # 193 
Principal Investigator: Juan Jimenez, MD 
Sponsor: Stryker Spine 
 
 
 
Funded by: Stryker Spine 
Version Number: 1.0 
September 21, 2018 
 
 
 
 
 
 
 
 

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1. Key Roles 
1.1. Principal Investigator: Juan Jimenez, MD 
Juan Jimenez, MD is a board-certified neurosurgeon, is qualified, and has the privileges to perform 
the surgical procedures described in this protocol. 
 
1.2. Co-Investigator(s): Charles Harvey, MD; Arun Jagannathan, MD; Jeff Coto, DNP, MS, RN, CCRN 
Charles Harvey, MD is a board-certified neurosurgeon, is qualified, and has privileges to perform the 
surgical procedures described in this protocol. 
 
Arun Jagannathan, MD is a board-certified diagnostic radiologist and is qualified to evaluate CT and 
X-ray imaging; however, to minimize bias, two different board-certified diagnostic radiologists who 
are blinded to the study hypotheses will evaluate spinal fusion post-implantation.  
 
Jeff Coto, DNP, MS, RN, CCRN, is an Assistant Professor of Nursing at Valparaiso University; his 
previous research experience makes him qualified to perform statistical analyses and interpret 
inferential statistics. 
 
1.3. Sub-Investigator(s): Brant Balthazor, PA; Kristin Balthazor, PA; Karim Bouferrache, PA 
 
1.4. Study Staff: Joseph Hanks, BS 
1.5. Institution: Riverside Medical Center 
 
2. Introduction: Background Information and Scientific Rationale 
2.1. Background Information 
2.1.1. Study Device 
Tritanium PL Cage 
The Tritanium Posterior Lumbar (PL) Cage is an Intervertebral Body Fusion implant intended for 
use as an aid in lumbar spinal fixation. This hollow, rectangular implant is offered in a variety of 
lengths, heights, widths and lordotic angles to adapt to a variety of patient anatomies. It has 
serrations on the superior and inferior porous surfaces of the implant for fixation, an 
ergonomically shaped anterior edge, and a flat posterior edge. The Tritanium PL Cage is 
manufactured out of Titanium Alloy Ti6Al4V (ASTM F1472). 
 
Regulatory Status 
United States: 
 
The Stryker Spine Tritanium PL cage is an intervertebral body fusion device indicated for use 
with autograft and/or allogenic bone graft comprised of cancellous and/or corticocancellous 
bone graft when used as an adjunct to fusion in patients with degenerative disc disease 
(DDD) at one level or two contiguous levels from L2 to S1. 
 
DDD is defined as back pain of discogenic origin with degeneration of the disc confirmed by 
history and radiographic studies. The DDD patients may also have up to Grade I 
spondylolisthesis at the involved level(s). 
 
These patients should be skeletally mature and have six months of nonoperative therapy. 

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 
Additionally, the Tritanium PL Cage can be used as an adjunct to fusion in patients 
diagnosed with degenerative scoliosis. 
 
The Tritanium PL Cage is to be implanted via a posterior approach. 
 
The Tritanium PL Cage is intended to be used with supplemental spinal fixation systems that 
have been cleared for use in the lumbosacral spine. 
2.1.2. Clinical, Epidemiological, or Public Health Background 
 
Degenerative Disc Disease (DDD) 
Degenerative Disc Disease is the pain, weakness, or potential numbness that stems from a 
degenerated disc in the spine. Every person undergoes disc degeneration as they age; however, as 
one’s spine is strained over time, the rigid outer shell of the disc weakens. As a result, the discs 
become less flexible and gradually collapses. In addition, a narrowing of the gap in the spinal column 
is observed. As the space between the vertebrae shrinks, additional pressure is placed on the discs, 
causing cracks or tears to appear. If the pressure is severe enough, it can force the jellylike fluid 
within the disc out through the tears, causing a herniated disc[Choi]. Diagnosis of DDD consists of an 
analysis of a patient’s medical history, as well as a physical exam to reveal muscle weakness, 
tenderness, or poor range of motion. A CT myelogram, CT scan, discograph, or  Magnetic Resonance 
Image (MRI) scan may be conducted to confirm the diagnosis[Taher]. 
 
Degenerative Scoliosis (DS)  
Degenerative scoliosis describes a side-to-side curvature of the spine caused by degeneration of the 
facet joints and intervertebral discs of the spine. The condition is associated with “progressive and 
asymmetric degeneration of the disc, facet joints, and other structural spinal elements” and may 
result in “neural element compression” [Kotwal]. Accelerated degeneration of a skeletally mature 
and previously straight spine is characterized by “minimal structural vertebral deformities, advanced 
degenerative changes, and a predominance of lower lumbar curves” [Kotwal]. Symptomatic patients 
may be treated with nonsurgical interventions, such as physical therapy and exercises, chiropractic 
manipulation, and yoga; surgical treatments include “decompression of neural elements” and/or 
fusion in order to restore and stabilize the “sagittal and coronal balance” [Kotwal]. 
 
Spondylolisthesis 
Spondylolisthesis is a condition in which a vertebra is mal-aligned in the sagittal plane with the 
vertebra below it, most often  occurring in the lower lumbar spine.  [Koreckj, TD]. The study devices 
are indicated for grade 1 spondylolisthesis, which accounts for approximately 75% of 
spondylolisthesis cases. Pain is described as intermittent and localized to the lower back,  
exacerbated by flexion and extension. Other symptoms include pain in the buttock region, 
numbness in the lower extremities, and/or loss of bowel and/or bladder control [Koreckj, TD]. 
Though conservative therapies like nonsteroidal anti-inflammatory drugs and exercise can be used 
to treat spondylolisthesis, severe cases often warrant surgical treatment, including decompression 
and/or  fusion [Sansur]. 
 
2.1.3. Importance of the study 
2.2. Scientific Rationale 

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Pain originating from the spine is the second most frequent cause for visits to a physician and “ranks 
fifth as the reason for hospital admission”[6]. The Agency for Healthcare Research and Quality 
published a brief that found spinal fusion was the 6th most frequently performed surgical procedure 
with about 490,000 cases performed annually[Holsgrove].  
 
It is hypothesized that the Tritanium PL Cage will result in satisfactory spinal fusion time in patients 
aged ≥ 21 years with degenerative disk disease and undergoing a spinal fusion in a one level or two 
contiguous levels from L2 to S1 compared to those who received PEEK implant as measured over a 
6-week, 3-month, 6-month and 12-month post-operative period. 
It is also hypothesized that participants implanted with the Tritanium PL Cage will report more 
improved back pain scores as measured by the Visual Analogue Scale (VAS), Oswestry Disability 
Index (ODI), 36-Item Short Form Survey (SF-36), Generic Health Status Survey (EQ-5D), and Press 
Ganey Patient Satifaction Survey. 
 
 
2.3. Potential Risks and Benefits 
2.3.1. Known Potential Risks  
 
The potential immediate and long-term risks associated with surgical implantation of the 
Tritanium PL Cage or PEEK implant are similar to other surgical procedures used to treat spinal 
instability and deformity. Risks associated with any surgical procedure include: 
 
 
Adverse reaction to anesthesia 
 
Hematoma or seroma at the operative site 
 
Failure to improve 
 
Persistent or worsened pain 
 
Infection of the wound 
 
Radiation exposure 
 
Wound dehiscence 
 
Vascular disorders, including thrombus 
 
Bronchopulmonary disorders, including emboli 
 
Genitourinary disorders 
 
Pneumonia 
 
Hemorrhage 
 
Myocardial infarction 
 
Paralysis  
 
Death 
In addition to the potential risks associated with general surgical procedures, patients who are 
implanted with the Tritanium PL Cage or PEEK implant may also be at risk for the following: 
 
Loss of proper spinal curvature, correction, height, and/or reduction 
 
Delayed union or nonunion 

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 
Neurological and spinal dura mater lesions from surgical traumaInfection or 
inflammation 
 
Nerve damage 
 
Paralysis 
 
Instrument failure resulting in a complication 
 
Allergic reaction to implanted materials 
 
Decrease in bone density due to stress shielding 
 
Dural leak requiring surgical repair 
 
Peripheral neuropathies 
 
Heterotopic bone formation 
 
Loss of bowel or bladder function 
 
2.3.2. Known Potential Benefits  
The expected potential benefits of spinal fusion using the Tritanium PL Cage or AVS UniLIF PEEK 
Spacer System are: 
 
Decrease in pain 
 
Improvement in back function 
 
Improvement in ability to work 
 
Improvement in ability to walk 
 
Improvement in health-related quality of life related to pain 
 
3. Objectives and Purpose 
3.1. Primary Objective 
 
The primary purpose of this study is to measure the efficacy of the Tritanium Posterior Lumbar Cage, 
by examining how robust the fusion is and how long it takes to achieve fusion of the spine. The 
results of this study may demonstrate that the Tritanium PL Cage is an effective option for patients 
that suffer from DDD.  
 
3.2. Secondary Objective(s) 
 
The secondary objectives of this study are to:  
 
 
Compare participants’ pre-surgical and post-surgical VAS, ODI, EQ-5D, and SF-36 scores to 
determine whether treatment with Tritanium or PEEK yields faster pain and quality of life 
improvement. 
 
Monitor device safety by gathering adverse event reports 
 
4. Study Design and Endpoints 
4.1. Description of the Study Design 

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This is a randomized, prospective, interventional, double-arm, single-blind, single-center, post-
market study conducted to evaluate the difference in fusion rate and speed between Stryker’s 
Tritanium PL Cage and Stryker’s AVS UniLIF PEEK Spacer System. 
4.2. Study Endpoints 
4.2.1. Primary Endpoint 
 
This study’s primary endpoint is time to fusion at post-operative follow-up, evaluated by 
radiologist interpretation of radiographic and CT imaging. 
 
 
4.2.2. Secondary Endpoint(s) 
 
The secondary endpoints are: 
 
 
Improvement in lower-back and leg pain VAS score at follow-up visits 
 
Improvement in ODI at follow-up visits 
 
Improvement in Quality of Life as measured by the SF-36 and EQ-5D at follow-up visits 
 
Serious adverse events 
 
Proportion of participants using narcotics 
 
Proportion of participants returning to work 
 
Proportion of participants relying on assistive ambulatory device 
 
Proportion of participants requiring revision/secondary surgical intervention 
 
5. Study Enrollment and Withdrawal 
5.1. Participant Inclusion Criteria 
In order to be eligible to participate in this study, an individual must meet all of the following 
criteria:  
 
Subject is skeletally mature.  
 
Subject has one or more of the following diagnoses:  
o Degenerative disc disease (DDD) at one level or two contiguous levels from L2 to S1.  
 
DDD may also include up to Grade I spondylolisthesis at the involved level(s).  
 
Note: DDD is defined as back pain of discogenic origin with degeneration of 
the disc confirmed by history and radiographic studies.  
o Degenerative scoliosis for which the Tritanium PL cage will be used as an adjunct to 
fusion. 
 
Subject has received six months of non-operative therapy.  
 
Subject understands the conditions of enrollment and is willing to sign and date the Informed 
Consent. 
 
Subject agrees to comply with visit schedule and study assessments. 
 
Provision of signed and dated informed consent form  
 
Stated willingness to comply with all study procedures and availability for the duration 
of the study  

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 
In good general health as evidenced by medical history.  
 
5.2. Participant Exclusion Criteria 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
 
 
Subject is older than 75 
 
Subject is younger than 21 
 
Subject is an obese (BMI > 40) patient, as that can produce loads on the spinal system which can lead 
to failure of the fixation of the device or to failure of the device itself.  
 
Subject is sensitive to titanium materials.   
 
Subject has an active infection at the operative site. 
 
Subject has marked local inflammation. 
 
Subject has any abnormality present which affects the normal process of bone remodeling including, 
but not limited to, severe osteoporosis involving the spine, bone absorption, osteopenia, primary or 
metastatic tumors involving the spine, active infection at the site or certain metabolic disorders 
affecting osteogenesis. 
 
Subject has any mental, trauma, or neuromuscular disorder which would create an unacceptable risk 
of fixation failure or complications in postoperative care. 
 
Subject has any open wounds. 
 
Subject is pregnant or plans to become pregnant during the course of the study. 
 
Subject has inadequate tissue coverage over the operative site. 
 
Subject has any neuromuscular deficit which places an unsafe load level on the device during the 
healing period. 
 
Subject has any condition of senility, mental illness, or substance abuse.  
 
Subject has any other medical or surgical condition which would preclude the potential benefit of 
spinal implant surgery, such as the presence of tumors, congenital abnormalities, elevation of 
sedimentation rate unexplained by other diseases, elevation of white blood cell count (WBC), or 
marked left shift in the WBC differential count. 
 
Subject has prior fusion at the levels to be treated. 
 
Subject is incarcerated. 
 
5.3. Strategies for Recruitment and Retention 
 
20 participants will be recruited for this study, and it is anticipated that 30 patients will need to be 
screened in order to reach the target enrollment. There is an anticipated accrual rate of 2 
participants per month. Participants will be recruited from the office of Neurosurgery Consultants. 
The study synopsis will be provided on Riverside’s research website; no other forms of 
advertisement are planned. 
 
Due to the long-term participation involved in this research study, participants will be contacted and 
provided with visit reminders when their visit date is approaching. In addition, to incentivize 
attending follow-up visits, participants will be compensated $25 per study visit in the form of a 
check.  

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5.4. Participant Withdrawal or Termination 
5.4.1. Reasons for Withdrawal or Termination  
 
Participants are free to withdraw from participation in the study at any time upon request.  
An investigator may terminate participation in the study if: 
 
 
Any clinical adverse event (AE), laboratory abnormality, or other medical condition or 
situation occurs such that continued participation in the study would not be in the best 
interest of the participant 
 
The participant meets and exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
 
Death 
 
Failure to follow-up 
 
Decision to withdraw informed consent 
 
Termination of the study 
 
5.4.2. Handling of Participant Withdrawals or Termination  
 
Participants who withdraw from the research study will still be scheduled for standard-of-care 
follow-up visits. The investigators will continue to perform protocol-specified follow-up 
procedures in order to capture adverse events, serious adverse events, and unanticipated 
problems. In addition, participants will be informed of which study device they received. 
 
5.5. Premature Termination or Suspension of Study 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspecting or terminating party to <investigator, funding agency, the IND/IDE 
sponsor and regulatory authorities>. If the study is prematurely terminated or suspended, the PI will 
promptly inform the IRB and will provide the reason(s) for the termination or suspension. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
 
Determination of unexpected, significant, or unacceptable risk to participants  
 
Demonstration of efficacy that would warrant stopping  
 
Insufficient compliance to protocol requirements  
 
Data that are not sufficiently complete and/or evaluable  
 
Determination of futility 
 
Study may resume after concerns about safety, protocol compliance, and data quality are 
addressed and satisfy the sponsor, IRB and/or FDA 

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6. Study Procedures and Schedule 
6.1. Study Procedures/Evaluations 
6.1.1. Study Specific Procedures 
 
6.1.1.1. Oswestry Disability Index 
 
The Oswestry Disability Index (ODI) measures impairment of daily living activities due to 
back pain. Greater impairment is associated with higher scores. ODI will be collected at 
screening and at each study follow-up visit.  
 
6.1.1.2. SF-36 
The Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered 
quality-of-life measures that rely upon patient self-reporting. This measure is utilized by 
managed care organizations and by Medicare for routine monitoring and assessment of 
care outcomes in adult patients. 
6.1.1.3. EQ-5D 
 
EQ-5D is a standardized health-related quality of life instrument that can be used in a wide 
range of health conditions and treatment. The instrument assesses five dimensions: 
mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The EQ-5D 
with 5 levels of severity for each of the 5 dimensions will be utilized in this study. 
 
 
6.1.1.4. Lumbar X-Ray with Flexion/Extension 
 
X-rays with flexion/extension will be obtained at baseline and at each follow-up visit 
interval (6-weeks, 3-months, 6-months, and 12-months). The x-ray technique is described 
in the Radiographic Guidelines section of this protocol. X-rays will be evaluated by two 
board-certified diagnostic radiologists who are blinded to the study’s hypotheses and 
objectives. 
 
6.1.1.5. CT Scan 
 
Low-dose CT imaging  of the index level(s) will be obtained at each follow-up visit interval 
(6-weeks, 3-months, 6-months, and 12-months). Parameters for performing the CT scan are 
provided in the Radiographic Guidelines section. The CT imaging will be evaluated by two 
board-certified diagnostic radiologists who are blinded to the study’s hypothesis and 
objectives. Analysis of the CT scan is described in the Radiographic Guidelines section of 
this protocol, located in Appendix B. 
 
6.1.2. Standard of Care Study Procedures  

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6.1.2.1. Radiologic Evaluation 
 
An MRI scan will be used to determine the diagnosis under the surgeon’s discretion. A 
lumbar plain x-ray with flexion/extension views will be obtained in cases of suspected 
spondylolisthesis. 
 
6.1.2.2. Subject Demographics 
 
Subjects’ age, sex, height, weight, Body Mass Index (BMI), race, and ethnicity will be 
gathered. 
 
6.1.2.3. Medical History 
 
Medical history will be obtained by interview and from medical records and will be 
recorded by the Research Coordinator in study-specific case reports. Baseline medical 
history including spinal conditions, physical examination findings related to the subject’s 
presenting condition, narcotic use, smoking status, and responses to quality of life and pain 
surveys.[SC1]  
 
Current medication history will be recorded at each visit, and a review of medication 
history will be performed during eligibility assessment. 
 
6.1.2.4. Physical Examination 
 
Physical examination, musculoskeletal examination and neurological examination  will be 
assessed.  
 
6.1.2.5. Adverse Event Assessment 
 
The PI will conduct an adverse event assessment at each follow-up visit to evaluate the 
safety of the implant. See section 8 Assessment of Safety for adverse event assessment 
and reporting procedures. 
 
6.1.2.6. Ambulatory Status 
 
The PI will record the date when the subject became completely ambulatory, defined as 
walking without any assistive device. Use of a cane, wheelchair, or walker will be recorded  
in the case report form at each visit. 
 
6.1.2.7. Work Status 
 
The PI will record whether the patient is working and indicate the hours per week of work 
that they are limited by back pain. 
 

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6.1.2.8. Visual Analog Scale (Leg Pain and Back Pain) 
 
The subject will mark a spot along a visual analog scale corresponding to back pain 
experienced in the last two weeks, where 0 represents no pain and 100 represents worst 
imaginable pain. This will be completed at baseline and at each study follow-up visit. 
Subjects will be instructed to only focus on lower back pain. A separate VAS item will assess 
leg pain using the same method described above.  
 
6.1.3. Standard of Care Surgical Procedure 
Subjects will undergo the Transforaminal Lumbar Interbody Fusion (TLIF) procedure within 30 
days of randomization unless there is a medically valid reason to postpone the surgery. A 
description of the surgical procedure is describe below, but a more thorough description is 
available in the Surgical Technique Manual, located in Appendix A. The PI and/or study 
coordinator will document key aspects of the surgical procedure in the study CRFs.  
 
The entire procedure is done under fluoroscopic or image assisted guidance with patient in the prone 
position. 
Step 1 
Exposure Open Approach 
 
Patient is placed under anesthesia and positioned in 
the prone position 
Step 2 
Preparation of Facet Joints 
 
Facet is prepared for fusion by removing the articular 
cartilage from the facet joint with a burr, rongeur, or 
other appropriate instrument. 
 
Inferior and superior articular facets are removed on 
the side of the TLIF. 
Step 3 
Insertion Site Preparation 
 
Tritanium PL cage may be inserted into the disc space 
using either a facet sparing or a transforaminal (TLIF) 
approach. 
 
An osteotome or high-speed drill may be used to 
remove the inferior articular process of the cephalad 
vertebra; if an osteotome is used, it may be done with 
two cuts. 
 
After both cuts are made, the inferior articulating 
process of the cephalad vertebra may be removed. 
 
A curette may be used to release the ligamentum 
flavum from the superior lamina of caudal vertebra, 
allowing for distraction. 
 
The ligamentum flavum may be preserved to minimize 
exposure of the neural elements. 
Step 4 
Distraction 
 
Minimal distraction may be required to insert the 
implant. 
 
Pedicle screw distraction, distraction between bony 
elements, and/or distraction with a positioning device 
may be used. 
 
Distraction should be removed when the implant is in 
the interbody space to minimize external compressive 
forces on the interbody space. 

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Step 5 
Discectomy 
 
Access to the disc space is achieved through an 
annulotomy made lateral to the posterior longitudinal 
ligament. 
 
Vertical cuts are made parallel to the dura and laterally 
in the foramen from the endplate of the cephalad 
vertebra to the endplate of the caudal vertebra. 
 
Additional cuts extend horizontally along the endplates 
of the vertebrae. 
 
Access to the disc space may also be gained using an 
osteotome at the superior endplate of the lower 
vertebra. 
Step 6 
Sizing the disc space 
 
Disc space height is sized using a series of paddle 
distractors, reamer distractors, or trials. 
 
Distractor size is serially increased until the appropriate 
fit within the disc space is achieved.  
Step 7 
Sizing 
 
A cage equivalent to the final Trial height or final 
distractor used is chosen. 
 
Implant sizing is based on the fit and feel of either the 
final Trial or distractor. 
Step 8 
Assemble Cage  
 
Align the threaded distal tip of the Inner Shaft with the 
threaded hole on the selected cage. 
 
Secure the cage to the Inserter by turning the knob on 
the Inner Shaft until the implant is tightly connected. 
Step 9 
Cage Insertion 
 
Cage is inserted gently and progressively into the disc 
space, using a mallet when necessary. 
 
Optimal positioning may be facilitated by directing the 
implant obliquely. 
Step 10 
Placement of Bone Graft 
 
Autograft is placed in the interbody space prior to 
insertion of the implant. 
 
Cage is filled with autograft prior to insertion, though 
additional bone graft may be placed lateral or dorsal to 
the implanted cage. 
Step 11 
Posterior Fusion 
 
Supplemental fixation of the lumbosacral spine will be 
obtained using Stryker’s ES2 Spinal System inserted at 
this time, if not inserted earlier.  
 
Compression of pedicle screws or interspinous device 
may be used to create segmental lordosis of the 
segment fused. 
Step 12 
Closure 
 
Foramen and TLIF site are checked for any bone 
fragments or extraneous tissue. 
 
Wound is closed in a routine manner. 
The following peri-operative data will be gathered from the participants’ medical records and entered 
into the surgery case report form: Operating Room time, anesthesia time, estimated blood loss, length 
of stay, neurological complications, operative and postoperative complications, and cage size. 
 

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6.2. Laboratory Procedures/Evaluations 
6.2.1. Standard of Care Clinical Laboratory Evaluations  
 
The following tests will be performed for all patients prior to spinal fusion: 
 
Complete Blood Count 
 
Basic Metabolic Panel 
 
Methicillin-Resistant Staphylococcus Aureus 
 
Urinalysis with Reflex 
 
Type and Screen 
 
The following tests will be performed for high-risk patients prior to spinal fusion: 
 
 
Electrocardiogram 
 
PT/PTT 
 
6.3. Study Schedule 
 
6.3.1. Screening/Enrollment/Baseline Visit 
 
Patients will be screened against inclusion and exclusion criteria at conventional care visits. The 
patient’s signature must be obtained on the informed consent form before performing any 
assessment that goes beyond the standard of care. A subject is enrolled in the study when the 
ICF is signed and the PI has determined that the subject meets all eligibility criteria. 
 
Enrollment/Baseline Visit (Visit 1) 
 
 
Obtain informed consent of potential participant verified by signature on study 
informed consent form 
 
Review medical history to determine eligibility based on inclusion/exclusion criteria.  
 
Review medications history to determine eligibility based on inclusion/exclusion criteria. 
 
Perform medical examinations needed to determine eligibility based on 
inclusion/exclusion criteria. 
 
Provide participants with instructions on CT and X-ray follow-up schedule 
 
Obtain urine pregnancy test for women of child-bearing age who have not had a 
hysterectomy/or sterilization 
 
Obtain demographic information, medical history, medication history, diabetes status, 
chronic steroid use, and alcohol and tobacco use history 
 
Record vital signs, results of examinations, other assessments 
 
Obtain participant’s responses on VAS, ODI, EQ-5D, SF-36, and Press Ganey Patient 
Satisfaction Scale. 
 
 Explain study follow-up schedule. 
 
Schedule x-ray with flexion and extension 

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 
Schedule surgical procedure  for participants who are eligible and available for the 
duration of the study. 
 
6.3.2. Follow-up Visit(s) 
 
6-Week Follow-up Visit (Visit 2) 
 
The 6-week follow-up visit must be performed between 35 and 49 calendar days post surgery. 
 
Record adverse events as reported by participant or observed by investigator. 
 
Record vital signs, results of physical examinations 
 
Obtain participant’s responses on VAS, ODI, EQ-5D, SF-36, and Press Ganey Patient 
Satisfaction Scale. 
 
Record participant’s adherence to treatment program. 
 
Obtain CT and X-ray of lumbar spine 
 
3-Month Follow-up Visit (Visit 3) 
The 3-month follow-up visit must be performed between 75 and 105 calendar days post-
surgery. 
 
Record adverse events as reported by participant or observed by investigator. 
 
Record vital signs, results of physical examinations 
 
Obtain participant’s responses on VAS, ODI, EQ-5D, SF-36, and Press Ganey Patient 
Satisfaction Scale. 
 
Record participant’s adherence to treatment program. 
 
Obtain CT and X-ray of lumbar spine 
 
6-Month Follow-up Visit (Visit 4) 
The 6-month follow-up visit must be performed between 165 and 195 calendar days post-
surgery. 
 
Record adverse events as reported by participant or observed by investigator. 
 
Record vital signs, results of physical examinations 
 
Obtain participant’s responses on VAS, ODI, EQ-5D, SF-36, and Press Ganey Patient 
Satisfaction Scale. 
 
Record participant’s adherence to treatment program. 
 
Obtain CT and X-ray of lumbar spine 
 
6.3.3. Final Study Visit 
 
Final Study Visit, 12-Month Follow-up Visit (Visit 5)  
 

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The 12-month follow-up must be performed between 350 and 380 calendar days post-    
surgery. 
 
Record adverse events as reported by participant or observed by investigator. 
 
Record vital signs, results of physical examinations 
 
Obtain participant’s responses on VAS, ODI, EQ-5D, SF-36, and Press Ganey Patient 
Satisfaction Scale. 
 
Record participant’s adherence to treatment program. 
 
Obtain CT and X-ray of lumbar spine 
 
6.3.4. Early Termination Visit 
 
If the participant is willing and it is not detrimental to his/her health, the study investigator 
should perform the following activities: 
 
 
Record adverse events as reported by participant or observed by investigator. 
 
Record vital signs, results of <specify examinations or other assessments, including the 
information to be recorded>.  
 
Obtain participant’s responses on VAS,ODI, EQ-5D, SF-36, and Press Ganey Patient 
Satisfaction Scale. 
 
Record participant’s adherence to treatment program. 
 
Obtain CT and X-ray of lumbar spine 
 
 
6.3.5. Unscheduled Visit 
 
Unscheduled visits will be handled like scheduled visits if they fall within the study windows. A 
case report form will be filled out in the same manner as a scheduled visit, but it will be noted 
that the visit was unscheduled. The reason for the unscheduled visit must be recorded.  
 
If the unscheduled visit falls outside of the study windows for a visit, the study investigator will 
provide conventional care (no study-specified CTs/X-rays will be obtained, no study-specific 
surveys will be administered). A CRF will be completed to monitor any change in participants’ 
well-being. The reason for the unscheduled visit must be recorded. 
 
 
6.3.6. Schedule of Events Table[SC2] 
7.3.8 Schedule of Events Table 
 
Procedure/Assessment 
 
Screening 
/ 
Baseline 
Procedure 
Discharge 
6 Weeks 
3 Months 
6 Months 
12 Months 

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Informed consent process, 
including informed consent 
signature 
X 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Physical Assessment and 
Vitals 
X 
 
 
X 
X 
X 
X 
Medical History 
X 
 
 
X 
X 
X 
X 
Medication History 
X 
 
 
X 
X 
X 
X 
Pregnancy test (urine)* 
X 
 
 
 
 
 
 
MRI 
X 
 
 
 
 
 
 
CBC, Basic Metabolic Panel, 
Methicillin-Resistant 
Staphylococcus Aureus, 
Urinalysis w/ Reflex, and 
Type and Screen 
X 
 
 
 
 
 
 
Electrocardiogram and 
Prothrombin Time/Partial 
Thromboplastin Time** 
 
 
 
 
 
 
 
X-Ray w/ Flexion and 
Extension 
X 
 
 
X 
X 
X 
X 
Lumbar Spine CT 
X 
 
 
X 
X 
X 
X 
Visual Analog Scale (VAS) 
X 
 
 
X 
X 
X 
X 
EQ-5D 
X 
 
 
X 
X 
X 
X 
Oswestry Disability Index 
(ODI) 
X 
 
 
X 
X 
X 
X 
SF-36 
X 
 
 
X 
X 
X 
X 
Adverse Event 
 
X 
X 
X 
X 
X 
X 
*For women of child-bearing potential  
**For high-risk patients only 
6.4. Concomitant Medications, Treatments, and Procedures 
All concomitant prescription medications taken during study participation will be recorded on the case 
report forms (CRFs). For this protocol, a prescription medication is defined as a medication that can be 
prescribed only by a properly authorized/licensed clinician. Medications to be reported in the CRF are 
concomitant prescription medications, over-the-counter medications and non-prescription medications. 
 
6.5. Prohibited Medications, Treatments, and Procedures 
Chiropractic care is discouraged; medications that interfere with bone deposition; 
chemotherapy; radiation to spine; and immuno-therapeutics 
 
7. Assessment of Safety 
 
7.1. Anticipated Adverse Events 
 

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The following anticipated adverse events (AE) for study subjects are identical to any other patient 
implanted with the Tritanium PL or PEEK Cage, regardless of study participation. 
 
7.1.1. Table 8.1.1.: Potential Adverse Events for Implantation of the Tritanium PL or PEEK Cage 
 
Anticipated Adverse Events for Implantation of the Tritanium PL Cage 
Late bone fusion 
Peripheral neuropathies 
No visible fusion mass 
Nerve damage 
Pseudarthrosis 
Heterotopic bone formation 
Implant weakening 
Neurovascular compromise, including paralysis, 
loss of bowel, bladder function, or foot-drop 
Superficial or deep-set infection 
Spine growth cessation of the fused portion 
Inflammatory phenomena 
Loss of proper spinal curvature, correction, 
height, and/or reduction 
Allergic reaction to implanted materials 
Delayed union or nonunion 
Decrease in bone density due to stress shielding 
Neurological and spinal dura mater lesions from 
surgical trauma 
Dural leak requiring surgical repair 
Early loosening resulting from inadequate initial 
fixation, latent infection, premature loading of 
the device, or trauma 
Bone Erosion 
Late loosening resulting from trauma, infection, 
biological complications or mechanical problems 
Pain 
Distraction or stress shielding of the graft or 
fusion mass caused by inappropriate or improper 
surgical placement of device 
Intraoperative fissure, fracture, or perforation of 
spine 
Postoperative fracture of bone graft or the 
intervertebral body above or below the level of 
surgery due to trauma, the presence of defects, 
or poor bone stock 
Spinal Surgery Complications 
Genitourinary Disorder 
Gastrointestinal Disorder 
Vascular Disorder, including thrombus 
Bronchopulmonary Disorder, including emboli 
Bursitis 
Hemorrhage 
Myocardial infarction 
Infection 
Paralysis 
Death 
 
7.2. Specification of Safety Parameters 
 
All adverse events, serious adverse events, unanticipated problems, and device deficiencies will be 
recorded in the CRF. A safety report will be completed and signed by the PI, detailing the event. The 
report will entail a summary of the event, including the date of its occurrence and the location of 
occurrence; a narrative of the event; description of any actions taken in response to the event; the 
subject’s participation status after the event; the subject’s prognosis; the PI’s evaluation of the 
event; the PI’s judgement concerning the need to revise the study protocol; the PI’s judgement 
regarding notification/re-consent of other subjects; and PI’s decision on future study conduct. 

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7.2.1. Definition of Adverse Events (AE) 
Adverse event means any untoward medical occurrence associated with the use of an intervention   
in humans, whether or not considered intervention-related (21 CFR 312.32 (a)). 
This definition includes events related to both the Tritanium PL Cage and PEEK implant and all 
procedures involved in this clinical investigation protocol. 
7.2.2. Adverse Device Effect (ADE) 
 
An adverse device effect is “any adverse event related to the use of an investigational medical 
device.” This definition includes events resulting from deficiencies or inadequacies in the instructions 
for use, the operation, the implantation, the installation, the deployment, or any malfunction of the 
medical device, including any event caused by use error or intentional misuse of the investigational 
medical device. 
 
7.2.3. Definition of Serious Adverse Events (SAE) 
An AE or suspected adverse reaction is considered "serious" if, in the view of either the investigator 
or sponsor, it results in any of the following outcomes: death, a life-threatening adverse event, 
inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant 
incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital 
anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or 
require hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. Examples of such medical 
events include allergic bronchospasm requiring intensive treatment in an emergency room or at 
home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse. 
 
7.2.4. Definition of Unanticipated Problems (UP) 
OHRP considers unanticipated problems involving risks to participants or others to include, in 
general, any incident, experience, or outcome that meets all of the following criteria: 
 
 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that 
are described in the protocol-related documents, such as IRB-approved research protocol 
and informed consent document; and (b) the characteristics of the participant population 
being studied; 
 
Related or possibly related to participation in the research (“possibly related” means there is 
a reasonable possibility that the incident, experience, or outcome may have been caused by 
the procedures involved in the research); and  
 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized. 
 

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This study will use the OHRP definition of UP and the investigators will consider the following 
corrective actions in the event that an UP is discovered: 
 
 
Modification of inclusion or exclusion criteria to mitigate the newly identified risks  
 
Implementation of additional safety monitoring procedures  
 
Suspension of enrollment of new participants or halting of study procedures for enrolled 
participants  
 
Modification of informed consent documents to include a description of newly recognized 
risks  
 
Provision of additional information about newly recognized risks to previously enrolled 
participants. 
 
 
7.3. Classification of an Adverse Event 
 
7.3.1. Severity of Event 
 
For AEs not included in the protocol defined grading system, the following guidelines will be 
used to describe severity. 
 
 
 
Mild – Events require minimal or no treatment and do not interfere with the 
participant’s daily activities.  
 
Moderate – Events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with functioning.  
 
Severe – Events interrupt a participant’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe events are usually potentially life-threatening 
or incapacitating. 
 
7.3.2. Relationship to the Study Device 
 
For all collected AEs, the clinician who examines and evaluates the participant will determine the 
AE’s causality based on temporal relationship and his/her clinical judgment. The degree of certainty 
about causality will be graded using the categories below. 
 
Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test 
result, occurs in a plausible time relationship to device implantation and cannot be explained by 
concurrent disease or other drugs or chemicals.  
 
Probably Related – There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal lab test result, occurs within a 
reasonable time after device implantation, is unlikely to be attributed to concurrent disease or other 
drugs or chemicals. 
 
Possibly Related – There is some evidence to suggest a causal relationship (e.g., the event occurred 
within a reasonable time after device implantation). However, other factors may have contributed 

20 
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to the event (e.g., the participant’s clinical condition, other concomitant events). Although an AE 
may rate only as “possibly related” soon after discovery, it can be flagged as requiring more 
information and may be upgraded as appropriate 
 
Unlikely to be Related – A clinical event, including an abnormal tab test result, whose temporal 
relationship to device implantation makes a causal relationship improbable (e.g., the event did not 
occur within a reasonable time after device implantation) and in which other drugs or chemicals or 
underlying disease provides plausible explanations (e.g., the participant’s clinical condition, other 
concomitant treatments).  
 
Not Related – The AE is completely independent of the study device implantation, and/or evidence 
exists that the event is definitely related to another etiology. There must be an alternative, definitive 
etiology documented by the clinician.] 
 
7.3.3. Expectedness 
 
The PI will be responsible for determining whether an AE is expected or unexpected. An AE will be 
considered unexpected if the nature, severity, or frequency of the event is not consistent with the 
risk information previously described for the study agent. The PI will indicate this on the adverse 
event report submitted to the IRB and study sponsor. 
 
7.4. Time Period and Frequency for Event Assessment and Follow-Up 
 
AEs and SAEs will be identified at scheduled follow-up visits and unscheduled visits made by the patient; 
in addition, AEs and SAEs will be identified when the PI is notified that the patient has entered the ED for 
any reason, utilizing Epic’s “in-basket” feature. The PI will follow-up on all suspected AEs and SAEs on a 
weekly basis for 3 weeks following the discovery of the adverse event or until enough information is 
gathered to complete an adverse event report. 
 
UPs will be recorded in the same manner that AEs and SAEs are reported; however, the following 
additional steps may be taken to ensure all subjects enrolled in the study are protected after the 
identification of an UP: 
 
 
If the presence of an unanticipated problem poses a safety risk for other participants, the 
Principal Investigator must ensure that all participants are re-consented with an informed 
consent form that reflects the acknowledgment of increased risk. 
 
If the unanticipated problem places subjects or others at a greater risk of physical or 
psychological harm than was previously known or recognized, the study may be suspended until 
the risk has been addressed or the study may be terminated. 
 
 
7.5. Reporting Procedures 
7.5.1. Adverse Event Reporting 
 
Any AE that occurs during the participant’s enrollment in the study will be recorded on the AE 
case report form. Pre-existing medical conditions or symptoms occurring prior to the initiation 

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Version 1.0 (9/21/18) 
 
of the study will not be reported as AEs, but an exacerbation of a pre-existing medical condition 
or symptom will be reported as an AE. Pain, neurological status, and functional impairment 
should be considered AEs when a participant’s complaint for any of these symptoms results in 
an unscheduled visit and/or when a participant presents with a new or worsening symptoms as 
compared to a previous visit. All AEs will be followed until the event is resolved or considered to 
be stable. 
 
IF an AE is ongoing when the participant completes the final visit, the AE will be followed until 
resolution or until 3 weeks after the final study visit has passed, whichever comes first. The 
study files must contain relevant source documents to confirm the occurrence of an AE and 
must be provided to the IRB upon request. 
 
What Event is Reported 
When is Event Reported 
By Whom is Event 
Reported 
To Whom is Event Reported 
Fatal or life-threatening 
unexpected, suspected 
serious adverse reactions 
Within 7 calendar days of 
initial receipt of information 
Investigator 
 
Local/Internal IRB 
 
Stryker’s Post Market 
Surveillance Team 
 
 
Sponsor or Designee 
 
FDA (if IND study) 
Non-fatal, non-life-
threatening unexpected, 
suspected serious adverse 
reactions 
Within 15 calendar days of 
initial receipt of information 
Investigator 
 
Local/Internal 
IRBs/Institutional Officials 
 
Stryker’s Post Market 
Surveillance Team 
 
 
Sponsor or Designee 
 
FDA (IND/Marketed 
Products) 
 
All participating 
investigators 
Unanticipated adverse device 
effects 
Within 10 working days of 
investigator first learning of 
effect 
Investigator 
 
Local/internal IRBs 
 
Stryker’s Post Market 
Surveillance Team 
 
 
Sponsor or Designee 
 
FDA (if IDE study) 
Unanticipated Problem that 
is not an SAE 
Within 14 days of the 
investigator becoming aware 
of the problem 
Investigator 
 
Local/internal 
IRBs/Institutional Officials 
 
Stryker’s Post Market 
Surveillance Team 
All Unanticipated Problems 
Within 30 days of the IRB’s 
receipt of the report of the 
UP from the investigator 
IRB 
 
OHRP 
 
 
Investigator 
 
IRB 
 
 
7.5.2. Serious Adverse Event Reporting 
 
Describe the SAE reporting procedures, including timeframes. Include description and a flow 
chart of when events are reported to various oversight and regulatory groups, and what study 
staff are responsible for completing and signing off on the SAE reports. Describe who will 
receive notification of SAEs.  

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Generally, any AE considered serious by the PI or Sub-investigator or which meets the definition 
of an SAE included in Section 8.1.2, Definition of Serious Adverse Event must be submitted on 
an SAE form to the DCC if one exists for the study. If a study is overseen by a Data and Safety 
Monitoring Board (DSMB), the DSMB may request to receive real-time notification of all SAEs or 
only SAEs thought to be related to study agent.  
 
According to 21 CFR 312.32(c)(1), “the sponsor must notify FDA and al participating 
investigators…in an IND safety report of potential serious risks, from clinical trials or any other 
source, as soon as possible, but in no case later than 15 calendar days after the sponsor 
determines that the information qualifies for reporting. The sponsor must report any suspected 
adverse reaction that is both serious and unexpected. The sponsor must report an adverse 
event as a suspected adverse reaction only if there is evidence to suggest a causal relationship 
between the drug and the adverse event, such as: 
 
 
A single occurrence of an event that is uncommon and known to be strongly associated with drug 
exposure (e.g., angioedema, hepatic injury, Stevens-Johnson Syndrome);  
 
One or more occurrences of an event that is not commonly associated with drug exposure, but is 
otherwise uncommon in the population exposed to the drug (e.g., tendon rupture); 
 
An aggregate analysis of specific events observed in a clinical trial (such as known consequences of 
the underlying disease or condition under investigation or other    events that commonly occur in 
the study population independent of drug therapy) that indicates those events occur more 
frequently in the drug treatment group than in a concurrent or historical control group. 
 
 
Furthermore, according to 21 CFR 312(c)(2, “the sponsor must also notify FDA of any 
unexpected fatal or life-threatening suspected adverse reaction as soon as possible but in 
no case later than 7 calendar days after the sponsor’s initial receipt of the information.”  
 
As noted previously, an unanticipated adverse device effect could be considered an SAE 
(Section 8.1.2, Definition of Serious Adverse Event). For IDE studies, according to 21 CFR 
812.150(a)(1), “an investigator shall submit to the sponsor and to the reviewing IRB a report 
of any unanticipated adverse device effect occurring during an investigation as soon as 
possible, but in no event later than 10 working days after the investigator first learns of the 
effect.” In addition, 21 CFR 812.150(b)(1), “A sponsor who conducts an evaluation of an 
unanticipated adverse device effect under 812.46(b) shall report the results of such 
evaluation to FDA and to all reviewing IRB's and participating investigators within 10 
working days after the sponsor first receives notice of the effect. Thereafter the sponsor 
shall submit such additional reports concerning the effect as FDA requests.”  
 
All deaths and immediately life-threatening events, whether related or unrelated, will be 
recorded on the SAE Form and submitted to the DCC/study sponsor within 24 hours of site 
awareness. See Section 1, Key Roles for contact information. 
 
Other SAEs regardless of relationship, will be submitted to the DCC/study sponsor within 72 
hours of site awareness 
 

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The study investigator shall complete an Unanticipated Adverse Device Effect Form and submit 
to the study sponsor and to the reviewing IRB as soon as possible, but in no event later than 10 
working days after the investigator first learns of the effect. The study sponsor contact 
information is provided in Section 1, Key Roles. The investigator and study sponsor are 
responsible for conducting an evaluation of an unanticipated adverse device effect and shall 
report the results of such evaluation to FDA and to all reviewing IRBs and participating 
investigators within 10 working days after the sponsor first receives notice of the effect. 
Thereafter the sponsor shall submit such additional reports concerning the effect as FDA 
requests. 
 
7.5.3. Unanticipated Problem Reporting 
 
Incidents or events that meet the OHRP criteria for UPs require the creation and completion of 
an UP report form. It is the site investigator’s responsibility to report UPs to their IRB and to the 
DCC/study sponsor. The UP report will include the following information: 
 
 
Protocol identifying information: protocol title and number, PI’s name, and the IRB 
project number;  
 
A detailed description of the event, incident, experience, or outcome; 
 
An explanation of the basis for determining that the event, incident, experience, or 
outcome represents an UP; 
 
A description of any changes to the protocol or other corrective actions that have 
been taken or are proposed in response to the UP. 
 
To satisfy the requirement for prompt reporting, UPs will be reported using the following 
timeline: 
 
 
UPs that are SAEs will be reported to the IRB and to the study sponsor within 10 days 
the investigator becoming aware of the event. 
 
Any other UP will be reported to the IRB and to the DCC/study sponsor within 10 days of 
the investigator becoming aware of the problem. 
 
All UPs should be reported to appropriate institutional officials (as required by an 
institution’s written reporting procedures), the supporting agency head (or designee), 
and OHRP within 10 days of the IRB’s receipt of the report of the problem from the 
investigator. 
 
An investigator shall submit to the sponsor and to the reviewing IRB a report of any 
unanticipated adverse device effect occurring during an investigation as soon as possible, but in 
no event later than 10 working days after the investigator first learns of the effect (21 CFR 
812.150(a)(1)), A sponsor who conducts an evaluation of an unanticipated adverse device effect 
under 812.46(b) shall report the results of such evaluation to FDA and to all reviewing IRB's and 
participating investigators within 10 working days after the sponsor first receives notice of the 
effect. Thereafter the sponsor shall submit such additional reports concerning the effect as FDA 
requests (21 CFR 812.150(b)(1)).  
 
 
 

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7.6. Study Halting Rules 
 
Implantation of the study devices will be halted when three grade 3 AEs determined to be “probably 
related” are reported to the IRB. The PI will notify the study sponsor and IRB immediately when the 
third grade 3 event is reported and the investigators will stop accepting new study participants.  
 
 
7.7. Study Oversight 
 
Safety oversight will be under the direction of Riverside’s Institutional Review Board, composed of 
individuals with the appropriate expertise, including medical doctors, community members with a 
scientific background, and nurses.  The IRB will conduct a comprehensive study audit and will meet at 
least semiannually to assess safety and efficacy data on each arm of the study. The IRB will provide its 
input to the study sponsor and study team. 
 
 
8. Clinical Monitoring 
 
Site monitoring is conducted to ensure that the rights and well-being of human subjects are protected, 
that the reported trial data are accurate, complete, and verifiable, and that the conduct of the trial is in 
compliance with the currently approved protocol/amendment(s), with GCP, and with applicable 
regulatory requirement(s). Monitoring activities include communication with the clinical investigator 
and study site staff; review of the study site’s processes, procedures, and records; and verification 
of the accuracy of data submitted to the sponsor. 
 
Clinical monitoring will be conducted by both the study sponsor and Riverside’s IRB. 
 
Riverside’s IRB will conduct the following monitoring activities: 
 
 
Annual audit of data collected from the study and study files 
 
Annual observation of informed consent process 
 
Monthly review of reported adverse events and protocol deviations and performance of risk 
assessment to determine the need for an action plan 
 
Stryker Spine will conduct the following monitoring activities: 
 
 
Regularly scheduled audits at critical phases of the study 
 
Review of complaint submissions by Stryker representatives 
 
9. Statistical Considerations 
9.1. Statistical and Analytical Plans 
 
The general statistical plan is outlined below. A detailed statistical analysis plan (SAP) will be developed 
and approved by the study sponsor and study principal investigator prior to analysis. 
 
9.2. Statistical Hypotheses 

25 
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Primary Efficacy Endpoint(s):  
Spinal Fusion 
 
Alternative Hypothesis: Implanting the Tritanium posterior lumbar cage results in 
satisfactory spinal fusion time in patients aged ≥ 21 years with degenerative disk disease and 
undergoing a spinal fusion in a one level or two contiguous levels from L2 to S1 compared to 
those who received PEEK implant as measured over a 6-week, 3-month, 6-month and 12-
month post-operative period 
 
Null Hypothesis: Implanting the Tritanium posterior lumbar cage does not result in an 
satisfactory spinal fusion time in patients aged ≥ 21 years with degenerative disk disease and 
undergoing a spinal fusion in a one level or two contiguous levels from L2 to S1 compared to 
those who received PEEK implant as measured over a 6-week, 3-month, 6-month and 12-
month post-operative period 
 
Secondary Efficacy Endpoints(s):  
 
Questionnaires 
 
Alternative Hypothesis: Participants implanted with the Tritanium posterior lumbar cage 
will report higher quality of life improvement, pain improvement, and disability 
improvement scores compared to participants implanted with the PEEK AVS uniLIF Spacer 
System as measured over a 6-week, 3-month, 6-month and 12-month post-operative period 
 
Null Hypothesis: There will be no difference between the quality of life, pain, and disability 
scores in participants that were implanted with the Tritanium or PEEK AVS uniLIF Spacer 
System as measured over a 6-week, 3-month, 6-month and 12-month post-operative period 
 
Adverse Events 
 
Alternative Hypothesis: There will be a difference in the number and severity of adverse 
events observed between participants who were implanted with the Tritanium posterior 
lumbar cage compared to participants who were implanted with the PEEK AVS uniLIF Spacer 
System as measured over a 6-week, 3-month, 6-month and 12-month post-operative period 
 
Null Hypothesis: There will be no difference in the number and severity of adverse events 
observed between participants who were implanted with the Tritanium posterior lumbar 
cage compared to participants who were implanted with the PEEK AVS uniLIF Spacer System 
as measured over a 6-week, 3-month, 6-month and 12-month post-operative period 
 
9.3. Description of Statistical Methods 
9.3.1. Analysis of the Primary Efficacy Endpoint(s) 
 
The primary endpoint analysis involves a comparison of participant fusion rates at 6-weeks, 3-
months, 6-months and 12-months after surgical intervention. All participants who were enrolled 
will be included in this analysis. Participants will be excluded from the analysis if a CT scan and x-
ray cannot be obtained at the 6-week visit. 
 
9.3.2. Analysis of the Secondary Endpoint(s) 
 

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Improvement in SF-36, EQ-5D, ODI, and VAS scores will be compared between groups using a 
repeated measure ANOVA (analysis of variance).  
 
The occurrence rate of adverse events will be assessed using a Kaplan-Meier approach and a 
comparison of serious adverse event rates will be made using a chi-squared analysis. 
 
9.3.3. Baseline Descriptive Statistics 
 
Descriptive statistics of all participants enrolled will be generated, including demographics and 
clinical diagnosis characteristics at baseline.  
 
9.4. Measures to Minimize Bias 
9.4.1. Enrollment/Randomization/Masking Procedures 
 
Study participants will be assigned to study groups by permuted block random assignment at 
the enrollment visit after a study investigator has determined that the participant meets all 
inclusion criteria and no exclusion criteria. The study participants will be blinded to which group 
they have been assigned.  
 
One potential bias that has been identified is the impact of knowing which device one has 
received on subsequent rating scales. Participants who are aware that they have been 
implanted with the Tritanium PL Cage may be more inclined to rate their pain as “improved.” To 
ensure participant survey responses are not confounded, participants will blinded to which 
study group he or she is assigned. 
 
Trial randomization codes will be tracked by the research coordinator by marking the designated 
section on study participants’ enrollment visit CRF. Planned unmasking will occur at the final 
study visit (12-month visit). Unplanned masking is defined as unmasking that occurs before the 
final study visit. If a study participant learns to which group he or she was assigned, it will be 
noted on his or her case report form that masking has been broken. The participant is still 
permitted to participate in the research study. 
 
Another potential bias that has been identified is the radiologists’ interpretation of the CT and X-
ray scans.  Radiologists who are not informed of the study’s hypotheses will perform CT and X-
ray evaluation to avoid bias in the interpretation of fusion rate. In addition, two radiologists will 
independently evaluate the fusion following the guidelines described in this protocol to 
establish inter-rater reliability. 
 
No dummy techniques will be necessary, as patients will be unable to determine with which 
device they’re implanted. Epic will be utilized to inform other health care providers that the 
implanted device should not be revealed to the participant. 
 
Study participants who discontinue early (at or before the 6-week study visit) may be replaced if 
the radiographic imaging was not performed. 
 
9.4.2. Evaluation of Success of Blinding 

27 
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Participants will be asked at each follow-up visit if he or she has become aware of which device 
he or she received. The research coordinator will record participants’ responses in the CRF. 
 
9.4.3. Breaking the Study Blind/Participant Code 
 
Provide the criteria for breaking the study blind or participant code. Discuss the circumstances in 
which the blind would be broken for an individual or for all participants (e.g., for SAEs). Indicate 
to whom the intentional and unintentional breaking of the blind should be reported.  
 
 
The study blind will be broken when: 
 
1. The participant leaves the study for any reason 
2. A serious adverse event occurs and the Institutional Review Board determines it is 
necessary for all participants to know device they received 
 
Intentional and unintentional breaking of the blind should be reported in the participant’s case 
report form. If unintentional, a protocol deviation report must be filled out by the PI and 
submitted to the IRB. 
 
9.4.4. Missing Data 
 
In evaluating primary endpoints, missing radiographic data will be excluded from the analysis. If 
6-week radiographic endpoints cannot be obtained, the participant will be removed from the 
study. 
 
In evaluating secondary endpoints, the following methods will be followed for including missing 
endpoint values 
 
 
Last observation carried forward 
 
All missing data are worst possible response 
 
All missing data are best possible response 
 
10. Source Documents and Access to Source Data/Documents 
 
Source data are all information, original records of clinical findings, observations, or other activities in a 
clinical trial necessary for the reconstruction and evaluation of the trial. Examples of these original 
documents and data records include, but are not limited to, hospital records, clinical and office charts, 
laboratory notes, memoranda, participant’ memory aids or evaluation checklists, pharmacy dispensing 
records, recorded audio tapes of counseling sessions, recorded data from automated instruments, 
copies or transcriptions certified after verification as being accurate and complete, microfiches, 
photographic negatives, microfilm or magnetic media, x-rays, and participant files and records kept at 
the pharmacy, at the laboratories, and medico-technical departments involved in the clinical trial. It is 
acceptable to use CRFs as source documents. If this is the case, it should be stated in this section what 
data will be collected on CRFs and what data will be collected from other sources.  

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11. Quality Assurance and Quality Control 
 
The study team will follow SOPs on data entry and storage. Any missing data or data anomalies will be 
communicated to PI for clarification/resolution. 
The study team will follow SOPs on staff training requirements, and a training tracking log will be 
maintained by the Research Coordinator and stored in the study binder. 
 
Following written SOPs and protocol, the monitors will verify that the clinical trial is conducted 
and data are generated, documented (recorded), and reported in compliance with the protocol, 
GCP, and the applicable regulatory requirements (e.g., Good Laboratory Practices (GLP)).  
The investigational site will provide direct access to all trial related sites, source data/documents, and 
reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and 
regulatory authorities. 
 
12. Ethics/Protection of Human Subjects 
12.1. 
Ethical Standard 
The principal investigator will ensure that this study is conducted in full conformity with Regulations 
for the Protection of Human Subjects of Research codified in 45 CFR Part 46, 21 CFR Part 50, 21 CFR 
Part 56.  
12.2. 
Institutional Review Board 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the Riverside Medical Center IRB for review and approval. Approval of both the protocol, 
consent form, and any recruitment materials must be obtained before any participant is enrolled. Any 
amendment to the protocol will require review and approval by the RMC IRB before the changes are 
implemented to the study. All changes to the consent form will be RMC IRB approved; a determination 
will be made regarding whether previously consented participants need to be re-consented. 
 
 
12.3. 
Informed Consent Process 
12.3.1. 
Consent Procedures and Documentation 
 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in 
the study and continues throughout the individual’s study participation. Extensive discussion of 
risks and possible benefits of participation will be provided to the participants and their families, 
if present. Consent forms will be IRB-approved and the participant will be asked to read and 
review the document. The investigator will explain the research study to the participant and 
answer any questions that may arise. All participants will receive a verbal explanation in terms 
suited to their comprehension of the purposes, procedures, and potential risks of the study and 
of their rights as research participants. Participants will have the opportunity to carefully review 
the written consent form and ask questions prior to signing. The participants should have the 
opportunity to discuss the study with friends, family, or their physician, or think about it prior to 

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agreeing to participate. The participant will sign the informed consent document prior to any 
procedures being done specifically for the study. The participants may withdraw consent at any 
time throughout the course of the trial. A copy of the informed consent document will be given 
to the participants for their records. The rights and welfare of the participants will be protected 
by emphasizing to them that the quality of their medical care will not be adversely affected if 
they decline to participate in this study. 
 
13.4 
Participant and Data Confidentiality 
 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and 
the study sponsor. This confidentiality is extended to cover the clinical information relating to 
participants. Therefore, the study protocol, documentation, data, and all other information 
generated will be held in strict confidence. No information concerning the study or the data will be 
released to any unauthorized third party without prior written approval of the Principal Investigator. 
 
13. Data Handling and Record Keeping 
13.1. 
Data Collection and Management Responsibilities 
 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site 
PI. The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness of 
the data reported.  
All source documents should be completed in a neat, legible manner to ensure accurate interpretation 
of data. Black ink is required to ensure clarity of reproduced copies. When making changes or 
corrections, cross out the original entry with a single line, and initial and date the change. DO NOT 
ERASE, OVERWRITE, OR USE CORRECTION FLUID OR TAPE ON THE ORIGINAL. 
 
Copies of the CRF will be provided for use as source documents and maintained for recording data for 
each participant enrolled in the study. Data reported in the CRF derived from source documents should 
be consistent with the source documents or the discrepancies should be explained and captured in a 
progress note and maintained in the participant’s study record.  
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and clinical 
laboratory data will be entered into paper case report forms. Clinical data will be entered directly from 
the source documents.  
13.2. 
Study Records Retention 
 
Study documents must be retained for a minimum of 3 years after the study’s closure. No records will 
be destroyed without the written consent of the sponsor, if applicable. It is the responsibility of the 
sponsor to inform the investigator when these documents no longer need to be retained. 
 
13.3. 
Protocol Deviations 
 

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A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or MOP requirements. 
The noncompliance may be either on the part of the participant, the investigator, or the study site staff. 
As a result of deviations, corrective actions are to be developed by the site and implemented promptly. 
 
It is the responsibility of the site to use continuous vigilance to identify and report deviations within 10 
working days of identification of the protocol deviation. All deviations must be addressed in study 
source documents. Study deviations must be sent to the IRB per Riverside’s guidelines. The site PI/study 
staff is responsible for knowing and adhering to IRB requirements.  
 
13.4. 
Publication and Sharing Policy 
 
Riverside and the PI retain the right to publish information related to the study so long as such 
publication or other public disclosure does not and is not reasonably anticipated to result in Stryker’s 
loss of rights in or to Confidential Information, or Research Inventions.  Prior to submission for 
publication of abstracts, manuscripts, presentations or other communications describing the results of 
any aspect of the study the party seeking to publish shall send Stryker a copy of each manuscript to be 
submitted via email to SpineClinical@stryker.com , and allow Stryker at least forty-five (45) days to 
review a copy of the material intended for publications in order to redact any Confidential Information, 
or Research Inventions therefrom.  Upon receipt of notice from Stryker Institution or Investigator shall 
expunge from any proposed publication or other public disclosure, and shall not publish or disclose, any 
information that Stryker reasonably believes would result in loss of rights in any Stryker Confidential 
Information, or Research Inventions or would otherwise compromise Stryker’s rights or interests.   
 
14. Study Administration 
14.1. 
Study Leadership 
 
 The Study Team will govern the conduct of the study. The Study Team will be composed of the Principal 
Investigator, the Operations Director, the Investigators, and the Research Coordinator. The Study Team 
will work closely together to carry out study activities and ensure compliance with the study protocol. 
14.2. 
Investigator Responsibilities 
 
The PI is responsible for ensuring that the research study is conducted in accordance with the clinical 
investigation plan, conditions of approval set by the RMC IRB, state and federal regulations, and ethical 
guidelines, affording the most protection to the subjects enrolled in this research study. 
 
The investigators agree to the following: 
 
 
The project will be performed by qualified personnel according to the RMC IRB-approved 
protocol. 
 
Make no changes or deviate from the research protocol, except to protect the life and 
physical well-being of a subject in an emergency; in the event of such a deviation, it will be 
documented and explained. 
 
The equipment, facilities, and procedures to be used in this research meet recognized 
standards for safety. 
 
No change will be made to the human subjects protocol or consent form(s) until approved 
by the RMC IRB. 

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 
Create and maintain source documents throughout the research study; ensure that all 
study-related materials are retained per institutional and protocol requirements. 
 
No subjects will be enrolled or data collected until the study is approved by the RMC IRB, 
and unless approval is current. 
 
Legally effective informed consent or assent will be obtained from all human subjects as 
required. 
 
Record, report, and assess every adverse event in accordance to the protocol; and report to 
the RMC IRB and sponsor all SAEs and device deficiencies that could have led to an SAE. 
 
Unanticipated problems, adverse events, and/or new information that occur in the course of 
the investigation that may affect the risk-benefit assessment for this research will be 
reported to the RMC IRB Office. 
 
Inform subjects of any new significant findings that occur during the study and provide 
him/her with procedures for possible emergencies related to the study, and make the 
necessary arrangements for emergency treatment. 
 
All named individuals on this project have read and understand the procedures outlined in 
the protocol and will be acting under my supervision. 
 
All named individuals on this project have completed the applicable CITI training program 
with a score of at least 80% or greater on every module, and have been given an 
opportunity to review the Belmont Report and The “Common Rule” (45 CFR Part 46). 
 
Student and guest investigators on this project are knowledgeable about the regulations 
and policies governing this research. 
 
I have read and understand the information in the Indications For Use document and 
Surgical Technique Manual, including potential side effects and risks of the device.  
 
I agree to maintain adequate and accurate records in accordance with the regulations and 
to make those records available for inspection in accordance with the regulations.  
 
I agree to cooperate with the IRB in the event it audits any or all of my IRB approved 
protocols to inquire about study progress or to observe the consent process that is used.  
 
I agree to meet with the investigator(s), if different from myself, on a regular basis to 
monitor study progress. 
 
If I will be unavailable, as when on sabbatical or other leave, including vacation, I will 
arrange for an alternate medical staff sponsor to assume responsibility during my absence. I 
will advise the RMC IRB by letter of such arrangements. 
 
I agree to promptly and completely comply with an IRB decision to suspend or withdraw its 
approval for the project. 
 
I agree to submit a final report to the IRB upon conclusion of the project.  
 
If  I, or my spouse, or dependent children have any significant financial interests* related to 
the work to be conducted as part of the project, including the pharmaceutical or medical 
equipment company and other entities whose financial interests would reasonably appear to 
be affected by the outcome of the study, I have disclosed them below. 
 
*Significant Financial Interests:  Income exceeding $5,000 including salary, consultant payments, 
honoraria, royalty payments, dividends, loan, or any other payments or consideration with value.  Equity 
in the form of stock, stock options, real estate, loan to, or any other investment or ownership interest 
exceeding $5,000 (current market value) or a 5% or greater ownership interest.  A management position 
(director, officer, partner, or trustee) with the interested entity. 
 
14.2.1.1. Delegation of Responsibility 
 

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The PI is responsible for providing training and supervision of study team members who 
perform tasks that are delegated by the PI. The PI is accountable for regulatory violations 
resulting from failure to adequately supervise the conduct of the research study. 
 
15. Conflict of Interest Policy 
 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical. Therefore any actual conflict of interest of persons who have a role in the design,  
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the trial. The study leadership in conjunction with the 
RMC IRB has established policies and procedures for all study group members to disclose all conflicts of 
interest and will establish a mechanism for the management of all reported dualities of interest. All 
members of the Study Team will disclose whether he/she or his/her spouse or dependent children have 
any significant financial interests related to the work to be conducted as part of the project, including 
the pharmaceutical or medical equipment company and other entities whose financial interests would 
reasonably appear to be affected by the outcome of the study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendix A: Radiographic Guidelines 
 
 
GE Optima CT660  
 
 
 
 

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Criteria for evaluating spinal bony fusion 
 
 
No lucent area around the implant 
 
No presence of herniated disk, central stenosis, lateral recess stenosis, foraminal stenosis, facet 
anthropathy. 
 
No fracture of the device, graft, or vertebra 
 
Visible bone formation in or about the graft material 
 
Less than 3 degrees of inter-segmental position change on flexion and extension views 
 
Presence of subsidence: a migration of more than 3mm  into the adjacent vertebra 
 
Proportion of bridging bone visually estimated over the surface area of the joint (i.e., 5%, 15%-
30%, etc.).