The Fusion Rate With K2M VESUVIUS® Demineralized Fibers Used With K2M EVEREST® Spinal System Compared to Autologous Bone Graft With Posterior Stabilization
Conditions: Spinal Stenosis, Spondylolisthesis, Degenerative Disc Disease
Sponsor: K2M, Inc.

K2M, Inc.  
 
 
 
           
 
K2M EVEREST/VESUVIUS Post Market Clinical Study Protocol 
Rev 1 March 3, 2015 
CONFIDENTIAL 
Page 1 of 38 
K2M Post Market Clinical Study Protocol  
  
The Fusion Rate with K2M VESUVIUS® Demineralized Fibers 
used with K2M EVEREST® Spinal System Compared to 
Autologous Bone Graft with Posterior Stabilization 
 
 
Clinical Protocol CA-003  
Revision 1 
March 3, 2015 
 
Sponsor: 
 
 
Contact: 
K2M, Inc. 
600 Hope Parkway SE 
Leesburg, VA 20175 
Marissa Conrad 
Director of Clinical Affairs 
Office: 866-526.4171 
Fax: 877-594-7206 
spineclinical@stryker.com 
www.k2m.com 
 
 
CONFIDENTIALITY STATEMENT 
This study is confidential in nature.  All information related to this study is considered proprietary and 
should not be made available to those not directly involved in this study.  Authorized recipients of this 
information include Investigators and Sub-Investigators, other health care personnel necessary to 
conduct the study, and Institutional Review Boards.   
The personnel provided with data from this study are hereby informed of its confidential and proprietary 
nature.  Release of these data to individuals other than those listed above requires the prior written 
permission of K2M, Inc. 

K2M, Inc.  
 
 
 
           
 
K2M EVEREST/VESUVIUS Post Market Clinical Study Protocol 
Rev 1 March 3, 2015 
CONFIDENTIAL 
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TABLE OF CONTENTS 
1 
PROTOCOL SYNOPSIS ................................................................................................................................ 4 
2 
INTRODUCTION ............................................................................................................................................ 6 
2.1 
Study Purpose ................................................................................................................................................................... 6 
2.2 
Background and Significance ............................................................................................................................................ 6 
2.3 
Device Description ............................................................................................................................................................ 6 
2.4 
Surgical Procedure ............................................................................................................................................................ 6 
2.5 
Indications for Use ............................................................................................................................................................. 6 
2.6 
Benefits and Risks ............................................................................................................................................................. 7 
2.6.1 
Potential Benefits ........................................................................................................................................................................ 7 
2.6.2 
Potential Risks ............................................................................................................................................................................. 7 
2.7 
Mitigation of Risks ............................................................................................................................................................. 7 
3 
INVESTIGATOR/SITE SELECTION .............................................................................................................. 8 
3.1 
Investigator Training .......................................................................................................................................................... 8 
4 
STUDY METHODS ........................................................................................................................................ 9 
4.1 
Study Design ..................................................................................................................................................................... 9 
4.2 
Treatment Group ............................................................................................................................................................... 9 
4.3 
Control Group – Comparative Data ................................................................................................................................... 9 
4.4 
Sample Size ...................................................................................................................................................................... 9 
5 
STUDY OBJECTIVES/OUTCOMES ............................................................................................................ 10 
5.1 
Primary Study Objective .................................................................................................................................................. 10 
5.1.1 
Radiographic Assessment of Fusion ......................................................................................................................................... 10 
5.2 
Primary Safety Objectives ............................................................................................................................................... 10 
5.2.1 
Device and Procedure Adverse Events .................................................................................................................................... 10 
5.3 
Secondary Objectives ..................................................................................................................................................... 10 
5.3.1 
Oswestry Disability Index .......................................................................................................................................................... 10 
5.3.2 
Visual Analog Scale .................................................................................................................................................................. 10 
5.3.3 
Health-Related Quality of Life ................................................................................................................................................... 11 
5.3.4 
Radiographic Assessments ....................................................................................................................................................... 11 
5.3.5 
Patient Satisfaction .................................................................................................................................................................... 11 
5.3.6 
Surgery Time ............................................................................................................................................................................. 11 
5.3.7 
Anesthesia Time ........................................................................................................................................................................ 11 
5.3.8 
Estimated Blood Loss ................................................................................................................................................................ 11 
5.3.9 
Length of Hospital Stay ............................................................................................................................................................. 11 
5.3.10 
Functional and Economic Status and Return to Work/School .................................................................................................. 11 
5.3.11 
Use of Narcotics Post-Surgery .................................................................................................................................................. 12 
6 
STUDY ENDPOINT ..................................................................................................................................... 13 
6.1 
Primary Study Endpoint ................................................................................................................................................... 13 
7 
STUDY POPULATION ................................................................................................................................. 14 
7.1 
Sample Size .................................................................................................................................................................... 14 
7.2 
Inclusion and Exclusion Criteria ...................................................................................................................................... 14 
7.3 
Study Duration ................................................................................................................................................................. 15 
8 
STUDY ENROLLMENT/EVALUATIONS..................................................................................................... 16 
8.1 
Patient Screening and Enrollment ................................................................................................................................... 16 
8.2 
Pre-Operative Evaluation ................................................................................................................................................ 17 
8.2.1 
Pre-Operative Assessment ....................................................................................................................................................... 17 
8.3 
Hospitalization/Surgical Technique/Discharge ................................................................................................................ 18 
8.3.1 
Surgery/Hospital Discharge Evaluation ..................................................................................................................................... 19 
8.4 
Post-Operative Follow-Up Visits ...................................................................................................................................... 19 
8.4.1 
Follow-Up Evaluation Data – Post-op through 24 Months ........................................................................................................ 20 
8.5 
Unscheduled Follow-up Evaluation ................................................................................................................................. 20 
8.6 
Schedule of Subject Evaluations ..................................................................................................................................... 21 
8.7 
Pregnancy During Study Participation (as appropriate) .................................................................................................. 22 
8.8 
Protocol Deviations ......................................................................................................................................................... 22 
8.9 
Subject Lost to Follow-Up ............................................................................................................................................... 22 
8.10 
Subject Withdrawal .................................................................................................................................................... 22 
8.11 
Study Case Report Forms.......................................................................................................................................... 22 

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List of Case Report Forms .......................................................................................................................................................................... 22 
9 
ADVERSE EVENTS .................................................................................................................................... 24 
9.1 
Definitions ........................................................................................................................................................................ 24 
9.1.1 
Adverse Event ........................................................................................................................................................................... 24 
9.1.2 
Serious Adverse Event .............................................................................................................................................................. 24 
9.1.3 
Subsequent Surgical Interventions ........................................................................................................................................... 24 
9.2 
Adverse Event Reporting ................................................................................................................................................ 25 
9.3 
Adverse Event Severity ................................................................................................................................................... 25 
9.4 
Adverse Event Association .............................................................................................................................................. 25 
9.5 
Potential Risks and Anticipated Adverse Events ............................................................................................................. 25 
9.5.1 
General Surgery Risks .............................................................................................................................................................. 25 
9.5.2 
Posterior Fusion Surgery Risks ................................................................................................................................................. 26 
9.5.3 
K2M Device Risks ..................................................................................................................................................................... 26 
10 
SITE REGULATORY REQUIREMENTS ..................................................................................................... 27 
10.1 
Institutional Review Board (IRB) Approval ................................................................................................................. 27 
10.2 
Study Specific Informed Consent ............................................................................................................................... 27 
10.3 
Regulatory Documents............................................................................................................................................... 27 
11 
SITE VISIT/MONITORING PROCEDURES ................................................................................................. 28 
11.1 
Site Qualification Visit ................................................................................................................................................ 28 
11.2 
Study Initiation Visit .................................................................................................................................................... 28 
11.3 
Periodic Monitoring Visits ........................................................................................................................................... 28 
11.4 
Final Close-Out Visit .................................................................................................................................................. 28 
12 
STATISTICAL METHODS ........................................................................................................................... 29 
12.1 
Study Design .............................................................................................................................................................. 29 
12.2 
Study Hypotheses ...................................................................................................................................................... 29 
12.3 
Sample Size ............................................................................................................................................................... 30 
12.4 
Analysis Populations .................................................................................................................................................. 30 
12.5 
Analysis of Primary Endpoint ..................................................................................................................................... 30 
12.6 
Safety Analyses ......................................................................................................................................................... 30 
12.7 
Supplementary Analysis............................................................................................................................................. 30 
12.8 
Methods to Minimize Bias .......................................................................................................................................... 30 
13 
SITE RESPONSIBILITIES ........................................................................................................................... 32 
13.1 
Investigator ................................................................................................................................................................ 32 
13.2 
Study Coordinator ...................................................................................................................................................... 32 
14 
RECORDS AND REPORTS ........................................................................................................................ 33 
14.1 
Investigator/Site Records ........................................................................................................................................... 33 
14.2 
Investigator/Site Reports ............................................................................................................................................ 33 
14.3 
Sponsor Records ....................................................................................................................................................... 34 
14.4 
Sponsor Reports ........................................................................................................................................................ 34 
15 
PUBLICATION POLICY .............................................................................................................................. 35 
APPENDIX 1 – Bone Marrow Aspiration & Hydration of VESUVIUS Demineralized Fibers ............................. 36 
APPENDIX 2 – SAP References ............................................................................................................................. 38 
 

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Rev 1 March 3, 2015 
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1 
PROTOCOL SYNOPSIS 
Primary Objective: 
To evaluate the perioperative and post-operative radiographic and patient 
outcome variables with the K2M VESUVIUS® Demineralized Fibers when used 
with the K2M EVEREST® Spinal System as compared to literature reported 
outcomes using autograft with posterior stabilization in the treatment of spinal 
stenosis, spondylolisthesis (grade 1 or 2), and/or degenerative disc disease. 
Study Design: 
Prospective, non-randomized (single arm) multi-center study 
Follow-Up Evaluations: 
Clinical evaluations will be conducted at initial post-op, 3 months, 6 months, 12 
months, and 24 months post-procedure. Adverse events will be monitored 
continuously. 
Outcome Assessments: 
Outcome measurements include the following: 
• Qualitative Radiographic and CT Assessments 
o Fusion Assessment 
o Device Status 
• Oswestry Disability Index (ODI)   
• Back, Hip/Buttock, and Leg Pain 10cm Visual Analog Scale (VAS) 
• SF-12v2 Health Survey 
• Operative Assessments 
o Estimated Blood Loss 
o Length of Operation 
o Time of Anesthesia 
• Length of Hospital Stay 
• Functional and Economic Status and Return to Work/School 
• Use of Narcotics Post-Surgery 
• Patient Satisfaction 
 
Safety Assessment: 
Safety will be assessed by: 
• The evaluation of all adverse events including but not limited to device related, 
procedure related, and additional serious adverse events 
 
Study Subjects: 
Patients eligible for study enrollment will require pedicle screw fixation for 
posterior stabilization as an adjunct to fusion at one or two spinal levels 
(contiguous) for spinal stenosis, spondylolisthesis (grade 1 or 2), and/or 
degenerative disc disease (DDD). Qualified patients will be confirmed by history 
and radiographic assessment.  Subjects under evaluation will be ≥ 18 years old 
at time of enrollment. 
Device Evaluation Group: 
VESUVIUS Demineralized Fibers (distributed by K2M, Inc. for LifeNet Health) 
used with the EVEREST Spinal System (K2M, Inc.) cleared for marketing and 
distribution under 510(k) K133944. 
Comparative Group: 
Historical, literature control of traditional spinal fusion intervention with posterior 
stabilization instrumentation and autograft. 
 

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Sample Size: 
Two-hundred four (204) total subjects at up to 15 clinical sites, geographically 
distributed throughout the US.  Sites are considered a Principal Investigator and 
their Sub-Investigators who are covered by a single Institutional Review Board’s 
(IRB’s) oversight and approval. 
Subject enrollment will be capped so that no single site contributes more than 
approximately 15% of the cases. 
 
 
Investigator Selection: 
 
• 
Appropriate patient population for trial indication 
• 
The Investigator must have completed a minimum of three surgeries using 
the EVEREST Spinal System. If a surgeon does not have experience with 
this, their first three (3) patients will be considered roll-in patients and the 
results from these patients will be analyzed against the entire cohort to 
determine if a learning curve exists.  If a surgeon has previously completed 
three (3) surgeries using the EVEREST Spinal System, there will be no 
stratification of their data. 
• 
Experience in clinical trial execution 
• 
Dedicated research infrastructure 
• 
Local institutional review board (IRB) for research oversight or ability to use 
central IRB 
• 
Standard of Care (SOC) compatible with protocol requirements 
o Radiographic imaging per protocol 
o Use/Collection of patient reported outcome measures – ODI; Back, 
Hip/Buttock, and Leg VAS; SF-12v2 
o Follow-up evaluations at initial post-op, 3 months, 6 months, 12 
months, and 24 months 
• 
Insofar as possible, sites for the study will be distributed regionally and by 
type of institution and level of investigator experience, patient volume and 
research experience so that any unanticipated and potentially prognostic 
factors may then be balanced both geographically and demographically in 
the study 
 
 

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2 
INTRODUCTION 
2.1 
Study Purpose 
The purpose of this study is to evaluate fusion status and patient outcomes observed from use of the VESUVIUS 
Demineralized Fibers with the EVEREST Spinal System as compared to the literature reported outcomes of spinal 
fusion using autograft with posterior stabilization.   
2.2 
Background and Significance 
Degenerative disc disease is a spinal condition caused by the breakdown of intervertebral discs. As a result of 
aging, the spine begins to show signs of wear and tear as the discs dry out and shrink. These age-related 
changes can lead to arthritis, disc herniation, or spinal stenosis, which can put pressure on the spinal cord and 
nerves and may cause back pain.  Spinal fusion is often utilized as the final treatment after conservative method 
attempts have failed. 
 
Although iliac crest graft is the gold standard for assisting instrumented fusion, alternatives to obviate the morbidity 
of graft harvest have become available. Specifically, the VESUVIUS Demineralized Fibers will be used in 
conjunction with the EVEREST Spinal System and results will be compared to those reported in literature after 
the utilization of autograft and posterior stabilization.  
2.3 
Device Description 
VESUVIUS Fibers are sterile freeze-dried allografts that are processed from donated human tissue, resulting from 
the gift of an individual or his/her family. The EVEREST polyaxial screw provides an increased range of motion 
and features a CoCr head to minimize head splay, optimized dual lead thread designed to increase fixation in 
bone, an Easy-to-Start set screw facilitating set screw introduction, and the ability to accept both 5.5 mm and 6.0 
mm diameter rods. Both K2M products are indicated for the uses described herein. 
 
The EVEREST Spinal System was cleared for marketing under 510(k) K133944. The VESUVIUS Demineralized 
Fibers are a Human Cell and Tissue Based Product (HCT/P) that is distributed by K2M, Inc. for LifeNet Health. 
 
2.4 
Surgical Procedure  
Implantation of the EVEREST Spinal System (K2M, Inc., Leesburg, VA) should be performed along with a 
posterolateral/transverse process fusion using VESUVIUS Demineralized Fibers (K2M, Inc., Leesburg, VA) as a 
graft extender.  Implantation is performed according to the standard of care of the Investigator, and in accordance 
with K2M’s Instructions for Use and Surgical Technique Manual for the EVEREST Spinal System and for the 
VESUVIUS Demineralized Fibers.  The use of an interbody spacer is optional. If an interbody spacer is used, a 
biocompatible PEEK cage must be implanted using the transforaminal lumbar interbody fusion (TLIF) technique.  
Refer to Section 8.3, for further details of the surgical technique. 
2.5 
Indications for Use 
VESUVIUS Demineralized Fibers are allograft material indicated for implantation in bony voids for tissue repair 
and are not intrinsic to the stability of the construct.  Allograft is commonly used as a bone graft extender to 
augment insufficient volumes of local autograft. The EVEREST Spinal System may be used in conjunction with 
the RANGE® (MESA® and DENALI®) Spinal Systems, all of which are cleared for the following indications: Non-
cervical fixation as an adjunct to fusion for the following indications: degenerative disc disease (defined as back 
pain of discogenic origin with degeneration of the disc confirmed by history and radiographic studies); 
spondylolisthesis; trauma (i.e., fracture or dislocation); spinal stenosis; curvatures (i.e., scoliosis, kyphosis and/or 
lordosis); tumor; pseudoarthrosis; and/or failed previous fusion.   

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Except for hooks, when used as an anterolateral thoracic/lumbar system the Everest Spinal System may also be 
used for the same indications as an adjunct to fusion.  When used for posterior non-cervical pedicle screw fixation 
in pediatric patients the Everest Spinal System implants are indicated as an adjunct to fusion to treat adolescent 
idiopathic scoliosis.  These devices are to be used with autograft and/or allograft.  Pediatric pedicle screw fixation 
is limited to a posterior approach. 
 
2.6 
Benefits and Risks 
2.6.1 
Potential Benefits 
There is no guarantee that the subject will experience any immediate or direct benefits with the use of the 
EVEREST Spinal System and/or the VESUVIUS Demineralized Fibers or for taking part in this study.  
 
2.6.2 
Potential Risks 
Potential risks include those associated with any spinal surgery resulting in neurological, cardiovascular, 
respiratory, gastrointestinal compromise, or death. A full listing of potential risks of the device and the surgical 
procedure can be found in Section 9.5 Potential Risks and Anticipated Adverse Events. 
2.7 
Mitigation of Risks 
Operative and acute periprocedural risks for the patients enrolled in this study are mitigated by restricting the use 
of the device to skilled neurological and orthopedic spine surgeons trained and experienced in the proper surgical 
technique to implant the respective device.  Long-term risks such as device failure or pseudoarthrosis are 
mitigated by proper patient selection and implanting the device in accordance with the Surgical Technique Manual 
for the EVEREST Spinal System and use of the surgical instruments provided by K2M and by following accepted 
standard of care in this population for spinal fusion surgery.  
 

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3 
INVESTIGATOR/SITE SELECTION  
The Investigators selected to participate in this clinical study will be responsible for conducting the study according 
to the requirements of the protocol.  Each site will have a designated Principal Investigator and may have Sub-
Investigators. Investigators/sites will be selected for participation in the study according to the following criteria: 
The Investigator/Site must have: 
• 
Expertise in clinical areas relevant to the study, including a background in spine surgery, sufficient 
experience in clinical research and an adequate patient population with adult spine disorders 
• 
Completed a minimum of three (3) surgeries using the EVEREST Spinal System. If a surgeon does 
not have experience with these, their first three (3) patients will be considered roll-in patients and 
the results from these patients will be analyzed against the entire cohort to determine if a learning 
curve exists.  If a surgeon has previously completed three (3) surgeries using the EVEREST Spinal 
System, there will be no stratification of their data. 
• 
Experience in participating in clinical studies and have adequate personnel and a dedicated research 
infrastructure including a Study Coordinator to adequately perform the tasks required by the clinical 
protocol 
• 
Local institutional review board (IRB) for research oversight or ability to use central IRB 
• 
A practice in a medical facility equipped appropriately to fulfill the surgical and patient contact 
requirements of the study 
• 
A standard of care (SOC) compatible with or capable of complying with the protocol requirements 
including but not limited to: 
• 
Radiographic imaging per protocol 
• 
Use/Collection of patient reported outcome measures – ODI; Back, Hip/Buttock, and Leg 
VAS; SF-12v2 
• 
Follow-up evaluations at initial post-op, 3 months, 6 months, 12 months, and 24 months 
• 
(Be willing to) sign a Clinical Research Agreement and abide by the agreement for the duration of 
the study. 
• 
(Be willing to) provide financial disclosure; including updating the disclosure during the study if the 
financial status changes 
The Investigators and practices in this trial are representative of the general user population of this type of device.  
Insofar as possible, sites for the study will be distributed regionally and by type of institution and level of 
investigator experience, patient volume and research experience so that any unanticipated and potentially 
prognostic factors may then be balanced both geographically and demographically in the study. 
 
3.1 
Investigator Training 
Training sessions in proper surgical technique and trial performance for the Principal Investigator, all Sub-
Investigators and research coordinators will be provided by the sponsor prior to initiation of the study at each site.   

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4 
STUDY METHODS 
4.1 
Study Design 
Prospective, non-randomized (single arm) multi-center study to evaluate the perioperative and post-operative 
radiographic and patient outcome variables of the VESUVIUS Demineralized Fibers and the EVEREST Spinal 
System compared to literature reported outcomes for traditional autograft and posterior stabilization treatment of 
spinal stenosis, spondylolisthesis, and/or degenerative disc disease (DDD). 
4.2 
Treatment Group  
Patients treated with the VESUVIUS Demineralized Fibers and EVEREST system that had/were:  
• 
Diagnosis of spinal stenosis, spondylolisthesis (grade 1 or 2), and/or degenerative disc disease 
(DDD). Qualified patients will be confirmed for inclusion by patient history and radiographic studies. 
• 
One or two contiguous levels requiring surgical intervention between L1-S1 
• 
Skeletally mature and ≥ 18 years old at time of enrollment 
4.3 
Control Group – Comparative Data 
Literature reported outcomes of adult patients (≥ 18 years old) with surgical intervention utilizing autograft and 
posterior stabilization for the treatment of spinal stenosis, spondylolisthesis and/or DDD. 
4.4 
Sample Size 
Two-hundred four (204) total subjects at up to 15 clinical sites, geographically distributed throughout the US. 
Sites are considered a Principal Investigator and their Sub-Investigators who function under the same institution 
and/or are covered by a single Institutional Review Board’s (IRB’s) oversight and approval. 
Subject enrollment will be capped so that no single site contributes more than approximately 15% of the cases. 
 

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Rev 1 March 3, 2015 
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5 
STUDY OBJECTIVES/OUTCOMES  
5.1 
Primary Study Objective 
The primary study objective is: 
5.1.1 
Radiographic Assessment of Fusion 
Radiographic assessments by CT scan at the 12 month visit and AP, lateral, Flex/Ext and oblique x-rays at the 
12 and 24 month visits include overall assessment of fusion.  Fusion will be graded by an independent radiologist 
taking into account signs such as: 
• 
Bony Bridging 
• 
Radiolucency 
• 
Development of Pseudoarthrosis 
5.2 
Primary Safety Objectives  
The primary safety objectives are: 
• 
The evaluation of all adverse events including device related, procedure related and additional serious 
adverse events. 
• 
Additional surgical intervention at the operative site including supplemental fixation, revision and/or 
device removal 
All adverse events will be documented on a continuous basis and reviewed by K2M Clinical Research Staff.  
Information regarding all device failures including implant breakage, subsidence, migration, or expulsion will be 
captured.   
5.2.1 
Device and Procedure Adverse Events 
Device and procedure adverse events will be documented and reported to the sponsor, including the need for 
removals, revisions, re-operations or supplemental fixation required to modify the device. 
5.3 
Secondary Objectives 
Secondary objectives are expected to further define the safety and patient outcomes for effectiveness of the K2M 
device.  Secondary objectives include:   
5.3.1 
Oswestry Disability Index 
The Oswestry Disability Index (ODI) is one of the principal condition-specific outcome measures used in the 
management of spinal disorders. The ODI is the most commonly used outcome measure in patients with low 
back pain. It has been extensively tested, showed good psychometric properties, and applicable in a wide 
variety of settings. This patient-reported outcome measure is a 10 item questionnaire that evaluates disability 
and functional impairment associated with back problems. This validated instrument includes items that relate to 
subjective symptomatology and activities of daily living (pain intensity, personal care, lifting, walking, sitting, 
standing, sex life, traveling). Each item is scored from 0 up to 5, with higher scores corresponding to greater 
disability.  A total ODI score is determined by adding the scores of the individual questions and dividing that total 
by the maximum possible score (i.e., 50 if all questions are answered) to yield a percentage. Therefore, the ODI 
score ranges from 0% to 100%. 
 
5.3.2 
Visual Analog Scale 
The severity of back, hip/buttock, and leg pain will each be evaluated in all study subjects using a 10-cm visual 
analog scale (VAS).  The study will employ a 15% improvement for success. 
 

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5.3.3 
Health-Related Quality of Life 
Health-related quality of life will be evaluated in all study subjects using the SF-12v2 Health Survey. This 
shortened and simplified version of the SF-36 makes the questionnaire less ambiguous for patients. It has a 
self-administered form that makes it easy to read and complete, and that reduces missing responses. The 
physical and mental component summary scales, referred to as PCS-12 and MCS-12 will be evaluated against 
published normative values and a 15% improvement in these scores will be used as an assessment of success. 
 
5.3.4 
Radiographic Assessments 
Qualitative radiographic assessment of the post-operative AP, lateral and oblique images will be performed by an 
independent radiologist.  Radiographic assessments being performed include, but are not limited to: 
• 
Posterior/Transverse process fusion, Right side (by level)  
• 
Posterior/Transverse process fusion, Left side (by level)  
• 
Anterior fusion, if TLIF procedure done, by level  
• 
Overall fusion by level  
• 
Device Condition 
• 
Device Subsidence 
• 
Device Migration 
 
5.3.5 
Patient Satisfaction 
At the 12 month and 24 month follow-up visits, subjects will be asked whether they were satisfied with the outcome 
of their surgery (Yes/No) and whether they would repeat the operation (Yes/No). 
 
5.3.6 
Surgery Time 
The length of the surgical procedure from the initial incision to final closure will be captured from the Anesthesia 
Record. 
 
5.3.7 
Anesthesia Time 
The length of time the patient is under anesthesia will be captured from the Anesthesia Record. 
 
5.3.8 
Estimated Blood Loss 
The amount of blood loss over the entire length of the surgery, documented on the Anesthesia Record will be 
captured. 
 
5.3.9 
Length of Hospital Stay 
The length of hospital stay from the date of admission to the date of discharge will be calculated. 
 
5.3.10 Functional and Economic Status and Return to Work/School 
The subject’s economic and functional status as well as ability to and the time it takes for the subject to be cleared 
to return to work/school, as judged by the Investigator, from the date of surgery will be documented.  Economic 
and functional status will be assessed using the Prolo Scale as modified by Voorhies in 2007.1 
 
                                                        
1 Voorhies RM, Jiang X, Thomas N “Predicting outcome in the surgical treatment of lumbar radiculopathy using the 
pain drawing score, McGill short form pain questionnaire, and risk factors including psychosocial issues and axial 
joint pain.” Spine J, 2007 7:516–524 

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5.3.11 Use of Narcotics Post-Surgery 
The types and dosages of any narcotics taken by the patient post-surgery will be documented. 
 

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6 
STUDY ENDPOINT  
6.1 
Primary Study Endpoint 
The endpoint of this study is the fusion status at 24 months. 
 

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7 
STUDY POPULATION 
7.1 
Sample Size 
A total of two-hundred four (204) total subjects at up to 15 clinical sites, geographically distributed throughout the 
US, will be enrolled.  
7.2 
Inclusion and Exclusion Criteria 
To be eligible to participate in the study, a subject must meet all of the Inclusion Criteria and none of the Exclusion 
Criteria.   
Inclusion Criteria 
1. Diagnosis of spinal stenosis; spondylolisthesis (grade 1 or 2); and/or degenerative disc disease (DDD) 
with one or two contiguous levels requiring fusion and adjunctive posterior stabilization between L1-S1. 
Qualified patients will be confirmed for inclusion by patient history and radiographic studies  
2. Willing and able to comply with the requirements of the protocol including follow-up requirements 
3. Willing and able to sign a study specific informed consent 
4. Skeletally mature and ≥ 18 years old at time of enrollment 
Exclusion Criteria  
1. Previous spine surgery at the index level 
(This is not intended to exclude previous microdiscectomies, microlaminotomies and other procedures that 
do not violate the disc space or that have not destabilized the spine, see also #2.) 
2. Previous posterior spine surgery (e.g., posterior decompression) that destabilizes the lumbar spine 
(Previous posterior spine surgery is intended to exclude destabilization at the target levels for the EVEREST 
surgical procedure. For example, previous laminectomies at the index levels will be excluded.) 
3. Active systemic infection or infection at the operative site 
4. Co-morbid medical conditions of the spine or upper/lower extremities that may affect the lumbar spine 
neurological and/or pain assessment  
5. Metabolic bone disease such as osteoporosis and osteopenia that contraindicates spinal surgery 
6. History of an osteoporotic fracture 
7. History of an endocrine or metabolic disorder (e.g., Paget's disease) known to affect bone and mineral 
metabolism 
8. Taking medications that may interfere with bony/soft tissue healing including chronic steroid use 
(Chronic steroid use is defined as any oral/systemic steroid use (this does not include inhaled, nasal, or topical 
steroids) for greater than 6 contiguous weeks within 3 months of the date of surgery; and /or >5 mg per day 
of oral steroids used daily within 2 weeks of the date of surgery.) 
9. Known allergy to titanium or cobalt chrome  
10. Rheumatoid arthritis or other autoimmune disease or a systemic disorder such as HIV, active hepatitis B 
or C, or fibromyalgia 
11. Insulin-dependent type 1 or type 2 diabetes 

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12. Medical condition (e.g., unstable cardiac disease, cancer) that may result in patient death or have an 
effect on outcomes prior to study completion 
13. Pregnant, or intends to become pregnant, during the course of the study 
14. Severe obesity (Body Mass Index > 40) 
15. Physical or mental condition (e.g., psychiatric disorder, senile dementia, Alzheimer's disease, alcohol or 
drug addiction) that would interfere with patient self-assessment of function, pain, or quality of life. 
16. Involved in current or pending spinal litigation where permanent disability benefits are being sought 
17. Incarcerated at the time of study enrollment 
18. Current participation in an investigational study that may impact study outcomes 
7.3 
Study Duration 
Study subjects will be expected to participate in this study for 24 months following surgery, with follow-up 
evaluations at initial post-op, 3 months, 6 months, 12 months, and 24 months.   
 

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8 
STUDY ENROLLMENT/EVALUATIONS  
8.1 
Patient Screening and Enrollment 
Consecutive patients who potentially meet the study inclusion and exclusion criteria will be screened for eligibility.  
The screening process will be as follows: 
• 
Consecutive patients are potentially eligible for entry into the study based on their age and whether their 
medical condition appears to generally fit the characteristics specific to this study. 
• 
Patients who agree to enter the study must sign the approved informed consent form. 
• 
A patient is considered enrolled in the study after signing the IRB approved informed consent.  Consented 
patients complete the remainder of the screening process to confirm study eligibility.  Patients who do 
not fulfill the screening criteria are considered Screening Failures and will be documented on the 
Screening and Enrollment Log.  Screening failures will not count against the total number of subjects 
eligible for analysis.   
• 
Diagnostic imaging studies (standing x-rays) MUST be completed within 180 days of the planned surgery. 
For diagnostic purposes, an optional pre-op MRI may also be done, per surgeon’s standard of care, but 
does not serve as a substitute for standing x-rays.  
• 
Subject self-assessment questionnaires must be completed within 90 days of the planned date of 
surgery. 
• 
Subjects who have signed the informed consent and fulfilled the Inclusion/Exclusion criteria are then 
scheduled for surgery.   
• 
If study surgery is unable to be completed within 90 days of the date of screening, the patient self-
assessment questionnaires must be repeated and the site must assess whether any imaging studies 
need to be repeated (these must be dated within 180 days of surgery).  If any imaging study is outside 
the screening window and has to be repeated, the subject must be exited from the study, re-consented, 
and assigned a new Subject ID number for re-screening. The Screening Log will provide a means to 
identify the original Subject ID number for any subjects who are rescreened.  
If, after qualifying for the study and before surgery, the subject experiences a significant change in his/her clinical 
presentation, the changes should be noted in the source documents and any screening tests and imaging 
repeated if medically indicated.  The patient self-assessment questionnaires must be repeated.  This subject need 
not be re-consented to continue the study if any repeated tests are medically indicated. The subject needs not be 
exited from the study unless the Investigator believes it is in the subject’s best medical interest to do so or that 
the subject no longer meets the eligibility criteria for the study.  The following should be considered when 
evaluating whether or not the change in clinical presentation is considered significant: an increase in related pain 
of approximately 3 points (on VAS scale from 0-10), a change in the location of the pain, deteriorating neurological 
status or other conditions where repeat radiographic studies may be necessary. The objective is to ensure that 
the patient still meets the eligibility criteria based on the medical judgment of the surgeon. 
The Subject ID number will be used to capture de-identified information. For this study, the following standardized 
format will be used: Site Identifying Number (2 digits)-Subject Identifying Number (3 digits). Your site identifying 
number will be assigned by the Sponsor, and the subject identifying number should start with 001 and continue 
accordingly during patient enrollment. For example, if the site identifying number issued to you is Site 03, and you 
are enrolling your second patient into the study, their Subject ID would be 03-002. A Patient Information Log will 
be provided to you to keep as a cross reference for study subjects. 

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8.2 
Pre-Operative Evaluation 
All subjects will complete the ODI, VAS, and SF-12v2 questionnaires within 90 days prior to the scheduled surgery.  
All patient questionnaires should be completed during the visit, preferably prior to the patient interacting with the 
Investigator or other clinical staff. A pertinent medical history will be documented and all subjects will undergo a 
standard neurological examination including assessments of sensation, motor function, and reflexes.   
8.2.1 
Pre-Operative Assessment 
• 
Informed consent 
• 
Inclusion/exclusion criteria 
• 
Demographics 
• 
Pertinent history and physical including current symptoms, height, weight, and tobacco use 
• 
Functional, Economic and Work/school status 
• 
Current medication for spine problem  
• 
Neurological Examination 
• 
AP and Lateral x-rays, ( must be completed within 180 days of planned date of surgery) 
• 
MRI (optional per standard of practice within 180 days of planned date of surgery) 
• 
Oswestry Disability Index; Back, Hip/Buttock, and Leg VAS; and SF-12v2 (within 90 days of planned date 
of surgery) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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8.3 
Hospitalization/Surgical Technique/Discharge 
Subjects will be admitted to the hospital according to the Investigator’s standard for an instrumented posterolateral 
fusion in conjunction with a TLIF surgery.  Prophylactic antibiotics, preoperative planning, patient positioning and 
anesthesia will be carried out in accordance with the institution’s and Investigator’s standard of care.  
Surgical Approach.  The surgeon performs a midline incision and standard posterior exposure to decorticate the 
transverse processes bilaterally to accommodate graft for the posterior fusion.  The spinous processes and 
interspinous ligaments can usually be left intact, which minimizes epidural scarring and provides a larger surface 
area for the posterior fusion. 
After exposure, the EVEREST Spinal System pedicle screws are placed bilaterally in accordance with K2M’s 
Instructions for Use and Surgical Technique Manual.  Fluoroscopy or other strategies may be used to aid in proper 
screw positioning.  Distraction may then be performed using the surgeon’s preferred method to open the posterior 
portion of the disc space, if needed.   
Transforaminal Lumbar Interbody Fusion (TLIF).  For the TLIF procedure, access to the disc space is gained 
via a triangular working window.  The window is formed by the traversing nerve root and thecal sac on the medial 
side, the exiting nerve root from the proximal vertebral level on the lateral side, and the superior aspect of the 
pedicle of the distal vertebra forms the base of the triangle.   The surgeon performs a laminotomy, laminectomy 
and/or facetectomy (partial or total) along with removal of the ligamentum flavum to provide access to the disc 
space.  Care should be taken to preserve the facets as much as possible and remove only enough bone as 
needed to provide access for introduction of the interbody spacer and to decompress and mobilize the nerve root 
as necessary.  If decompression of the contralateral side of the spinal canal is required, the TLIF procedure can 
be modified to include a central laminectomy.   
 
After exposure of the posterior aspect of the disc, an incision is made in the annulus through which the discectomy 
and endplate preparation are performed.  Endplate preparation consists of removal of the cartilaginous endplate 
down to bleeding bone.   The interbody spacer (a biocompatible PEEK spacer of the surgeon’s choice) is then 
introduced.  
The TLIF approach with the EVEREST Spinal System also allows for auxiliary procedures for decompression of 
the spinal cord, correction of spondylolisthesis, correction of disc space collapse or mild kypohsis, as may be 
medically indicated. 
Once the interbody implant is in place and bone graft added to the disc space, distraction is released and 
compression is applied to the pedicle screw to load the anterior implant and restore lordosis to the spine.   
Posterolateral/Transverse Process Fusion and use of VESUVIUS Demineralized Fibers.  For each level of 
the posterolateral fusion, local bone (amount used is to be estimated and recorded) is supplemented with 
VESUVIUS Demineralized Fibers and bone marrow aspirate (BMA)2.  The Fibers and BMA are to be combined 
in a 3:2 volumetric ratio (i.e., a minimum of 15cc Fibers and 10ml BMA are required for a one-level case).  If BMA 
volumes are insufficient to achieve a 3:2 ratio, BMA may be supplemented with venous-line blood.  The bone 
graft, extended with a minimum of 15cc VESUVIUS Fibers and 10ml BMA per level, is then evenly distributed to 
the right and left lateral gutters.  Local bone may be obtained from the levels to be fused, as well as from no more 
than one additional level of decompression above the target level(s).   
The interspinous ligament, if preserved, will serve to prevent graft migration into the exposed portion of the spinal 
canal and foramen.  Care must be taken when placing graft on the ipsilateral intertransverse region to avoid 
allowing graft to enter the spinal canal or compress the exiting nerve root.  Before closure, inspect the neurologic 
elements to ensure that no graft material has fallen into the spinal canal. 
                                                        
2 Obtained from the anterior iliac crest and/or vertebral body (refer to detailed instructions provided in Appendix 1 of this protocol) 

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Surgical Close and Recovery.  Standard procedures and precautions are to be followed for closure of the 
surgical incision and postoperative recovery.  The patient is typically mobilized out of bed the day after surgery; 
bracing is not required but can be used according to surgeon preference.  The subject may be instructed to return 
to normal activity at the discretion of the Investigator. 
Additional post-operative restrictions may be imposed according to the standard of care normally utilized by the 
Investigator.  In addition, subjects should be instructed to notify the Investigator if experiencing untoward events 
including but not limited to noticeable pain, numbness, tingling, or weakness that does not decrease with rest, 
swelling of the lower extremities that does not decrease, or increased pain, erythema, edema or drainage from 
the surgical incision.  The Investigator should then determine if an evaluation is warranted. 
A Subject may be withdrawn from the study intra-operatively at the discretion of the Investigator if unexpected 
findings/occurrences dictate deviation from the intended study procedure. Justification for an intra-operative 
withdrawal and alternative surgical procedure must be fully documented in the subject’s medical record and on 
the Study Exit case report form.   
8.3.1 
Surgery/Hospital Discharge Evaluation 
Surgery Data – Data points required on the Operative case report form must be documented at the time of 
surgery, including intra-operative adverse events. 
• 
Date of Hospital Admission 
• 
Date of Surgery 
• 
Date of Hospital Discharge 
• 
Implanting Surgeon 
• 
Implanted System Details (screw and rod size, connector use, etc.) 
• 
Surgery Detail/Concomitant Procedures 
• 
Surgery Time (initial incision to closure) 
• 
Anesthesia Time 
• 
Perioperative Antibiotic Use 
• 
Estimated Blood Loss 
• 
Quantity of VESUVIUS Demineralized Fibers, Bone Marrow Aspirate and Local Bone Used 
• 
Adverse Event Assessment 
 
If the patient experienced an adverse event(s) during the hospitalization it should be documented and 
recorded on an Adverse Event case report form.   
8.4 
Post-Operative Follow-Up Visits 
All subjects will be required to return for follow-up visits at initial post-op, 3 months, 6 months, and 12 months, 
and 24 months post-procedure.  (A “wound check only” visit does not require data collection unless there is an 
adverse event.  Then this would be captured as an Unscheduled Visit, and an Adverse Event CRF would be 
completed.)   
 
Data collected at each follow-up visit must be confirmable by source documents and the appropriate case report 
forms must be completed.  All patient questionnaires should be completed at the visit, preferably prior to the 
patient interacting with the Investigator or other clinical staff.  Post-operative follow-up visit requirements are as 
follows:  

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8.4.1 
Follow-Up Evaluation Data – Post-op through 24 Months 
• 
Functional, Economic and Work/school Status (including release for return to work/school) (initial 
post-op, 3 month, 6 month, 12 month, and 24 month) 
• 
Current Symptoms (all visits) 
• 
Medication (taken for spine problem since last contact) (initial post-op, 3 month, 6 month, 12 month, 
and 24 month) 
• 
Neurological Examination (initial post-op, 3 month, 6 month, 12 month, and 24 month) 
• 
AP, Lateral, Oblique and Flex/Ext x-rays (6 month, 12 month, and 24 month) 
• 
Oswestry Disability Index (initial post-op, 3 month, 6 month, 12 month, and 24 month) 
• 
Back, Hip/Buttock, and Leg VAS (initial post-op, 3 month, 6 month, 12 month, and 24 month) 
• 
SF-12v2 (initial post-op, 3 month, 6 month, 12 month, and 24 month) 
• 
Adverse Event Assessment (all visits) 
• 
CT Scan (12 month) 
• 
Patient Satisfaction (12 month, 24 month) 
• 
Study Exit 
8.5 
Unscheduled Follow-up Evaluation 
Subjects may return to the clinic at a time point that is not a scheduled follow-up visit.  If the Investigator determines 
that the return visit is related to the study device, procedure or surgery, the Unscheduled Visit portion of the Post-
Operative Follow-Up case report form should be completed.  If a subject requires a device or procedure related 
re-operation including supplemental fixation, revision and/or device removal as a result of an unscheduled visit 
the Sponsor should be notified immediately and an Adverse Event case report form should also be completed.  
 
 

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8.6 
Schedule of Subject Evaluations 
Interval → 
Assessment ↓ 
Pre-op 
Operative/
Discharge 
Initial F/U 
(discharge-8 
weeks post-op) 
3 Month 
F/U (± 2 
weeks) 
6 Month 
F/U (± 1 
month) 
12 Month 
F/U (± 2 
months) 
24 Month 
F/U (±2 
months) 
Unscheduled 
Visit 
Informed Consent 
X 
 
 
 
 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
 
 
 
 
Demographics  
X 
 
 
 
 
 
 
 
Pertinent History 
X 
 
 
 
 
 
 
 
Current Symptoms 
/ Complaints & 
Findings 
X 
 
X 
X 
X 
X 
X 
 
Functional, Econ., 
Work/school 
Status 
X 
 
X 
X 
X 
X 
X 
 
Medications for 
Spine Problems  
X 
 
X 
X 
X 
X 
X 
 
Neurological 
Examination 
X 
 
X 
X 
X 
X 
X 
 
ODI 
X 
 
X 
X 
X 
X 
X 
 
Back, Hip/Buttock, 
and Leg VAS 
X 
 
X 
X 
X 
X 
X 
 
SF-12v2 
X 
 
X 
X 
X 
X 
X 
 
Patient 
Satisfaction 
 
 
 
 
 
X 
X 
 
Hospitalization and 
Surgery Data 
 
X 
 
 
 
 
 
 
Adverse Event 
Assessment 
 
X 
X 
X 
X 
X 
X 
X 
AP & Lateral  
x-rays 
X 
 
 
 
X 
X 
X 
If needed 
Flex/Ext x-rays 
 
 
 
 
X 
X 
X 
 
Oblique (right, left) 
x-rays  
 
 
 
 
X 
X 
X 
 
CT Scan 
 
 
 
 
 
X 
 
 
Study Exit  
 
 
 
 
 
 
X 
 
 
 
 

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8.7 
Pregnancy During Study Participation (as appropriate) 
If a subject becomes pregnant during the study, the sponsor should be notified as soon as possible.  The subject 
will remain in the study, but during the pregnancy the study follow-up visit(s) will be modified to exclude the X-ray 
imaging requirements.  At follow-up visits after the pregnancy, the required X-rays should again be performed.  
Information related to the pregnancy and outcome should be maintained by the site and documented by the 
Sponsor in monitoring reports during periodic visits. 
8.8 
Protocol Deviations 
The Protocol must be followed closely, and the Investigators should not deviate from the protocol unless in the 
opinion of the Investigator a deviation from the protocol is in the best interest of safety for the subject.  A deviation 
from the protocol should be reported to the sponsor as soon as possible after the deviation is noted.  In addition, 
during routine monitoring visits the monitor may determine a protocol deviation and initiate the protocol deviation 
process.  All protocol deviations must be documented on a Protocol Deviation case report form.  For the scientific 
integrity of the study, protocol deviations must be kept at a minimum.  If the site has an unacceptable number of 
protocol deviations that cannot be explained due to patient safety, the issue will be discussed with the site and 
corrective action will be considered. 
In the event a patient questionnaire is not completed during a visit, permission may be obtained from the Sponsor 
to have the questionnaire mailed into the site within a reasonable amount of time.  
8.9 
Subject Lost to Follow-Up 
Every attempt will be made to have all subjects complete the follow-up visit schedule as specified in the protocol.  
A subject will not be considered lost to follow-up unless efforts to obtain compliance are unsuccessful.  If a subject 
misses a follow-up visit, the site must document attempts to contact the subject by phone twice.  If both contact 
attempts are unsuccessful, a certified letter from the Investigator must be sent to the subject’s last known address 
indicating the subject’s commitment to the study and site contact information to arrange a visit.  If the subject does 
not respond, only then will the subject be considered lost to follow-up.  If a subject is lost to follow-up, a Study Exit 
case report form, including a full description of the attempts to locate the subject, must be completed. 
8.10 Subject Withdrawal 
Subjects have the right to withdraw their consent at any time during the study.  If a subject requests to withdraw 
from the study, all information regarding the subject’s withdrawal and disposition must be recorded in the subject’s 
medical record.  A Study Exit case report form, including a full description of the circumstances related to the 
withdrawal, must be completed. 
8.11 Study Case Report Forms  
The Sponsor will provide Case Report Forms (CRFs) to the sites for the study.  Visit or evaluation specific as well 
as additional CRFs to complete as needed are included.  Data should be entered with a black pen on the specified 
locations of the CRFs.  If an error is made on a CRF, the incorrect entry should be crossed out with a single 
horizontal line, the correct entry written next to it, and the correction initialed and dated by the person making the 
correction.  Copies of the CRFs for the study are included as an appendix to the protocol. 
List of Case Report Forms 
• 
Inclusion/Exclusion 
• 
Pre-operative 
• 
Operative/Discharge 
• 
Follow-up form covering: 
o Initial Post-Op Follow-up Visit (discharge to 8 weeks post-op) 
o 3 Month Follow-up Visit ± 2 weeks 

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o 6 Month Follow-up Visit ± 1 month 
o 12 Month Follow-up Visit ± 2 months 
o 24 Month Follow-up Visit ± 2 months 
o Unscheduled Visit 
• 
Subject Questionnaires including Oswestry Disability Index; Back, Hip/Buttock, and Leg Visual 
Analog Scale (VAS); SF-12v2; and Patient Satisfaction 
• 
Adverse Event  
• 
Protocol Deviation  
• 
Study Exit 

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9 
ADVERSE EVENTS 
9.1 
Definitions 
9.1.1 
Adverse Event 
An Adverse Event (AE) is defined as any untoward medical occurrence in a subject undergoing surgery in this 
trial which does not necessarily have a causal relationship with this intervention.  An AE can, therefore, be any 
unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of the one of the devices, whether or not the event is considered causally related to the 
use of the device.  Any worsening of a pre-existing condition or illness is considered an AE.  Laboratory 
abnormalities and changes in vital signs are considered to be AEs only if they result in discontinuation from the 
study, necessitate therapeutic medical intervention that could impact the study’s surgical outcomes, and/or if the 
Investigator considers them to be AEs. 
 
9.1.2 
Serious Adverse Event 
Any AE that results in one or more of the following is considered a Serious Adverse Event (SAE): death, life 
threatening situation, inpatient hospitalization, persistent or significant disability/incapacity, and other medically 
important events.  Definitions of SAEs are: 
Death: the subject dies during participation in the study. 
Life threatening situation: the subject is at risk of death at the time of the event, but does not refer to the 
hypothetical risk of death if the AE were more severe or were to progress.   
Inpatient hospitalization: a subject requires hospitalization or prolongation of an existing hospitalization, 
including medical or surgical intervention to prevent permanent impairment to a body structure or body 
function during participation in a clinical study. 
Persistent or significant disability/incapacity: any AE having an outcome that is associated with a 
substantial disruption of the ability to carry out normal life functions.  This includes the inability to work, but is 
not intended to include transient interruptions of daily activities.   
Other medically important events: important medical events that may not result in death, be life-
threatening, or require hospitalization (including emergency room visits) but may be considered a serious AE 
when, based upon medical judgment, they may jeopardize the subject. 
Reports of all Serious Adverse Events (SAEs), as classified by the Investigator, will be reviewed on a periodic 
basis by the Medical Monitor.   
9.1.3 
Subsequent Surgical Interventions 
The cause for subsequent surgical interventions should be listed as a serious adverse event. 
Subsequent surgical interventions are classified as follows: 
Revision: a procedure that adjusts or in any way modifies the original implant configuration. A revision may 
also include adjusting the position of the original configuration. 
Removal: a procedure where all of the original system configuration are removed with or without replacement.  
Supplemental Fixation: a procedure in which additional instrumentation not under study in the protocol is 
implanted. 
Reoperation: any surgical procedure at the involved level that does not require removal, modification, or 
addition of any components to the system.  

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9.2 
Adverse Event Reporting 
Any AE that occurs during the subject’s participation in the study will be recorded on the Adverse Event case 
report form.  Pre-existing medical conditions or symptoms occurring prior to the initiation of the study will not be 
reported as AEs but a worsening 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 subject’s complaint for any of 
these symptoms results in an unscheduled visit or when a subject presents with 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.  Relevant source documentation 
must be available to confirm the occurrence of an AE and must be provided to the sponsor upon request. 
9.2.1 
Serious Adverse Event Reporting 
Independent of the relationship to the study device or procedure, the site must report SAEs to the Sponsor 
immediately upon becoming aware of the events and subsequently submit the appropriate CRFs within 10 working 
days.  SAEs will be investigated and reported to the FDA if they fall within the appropriate guidelines for Medical 
Device Reporting (MDR). The site must also report SAEs to the reviewing Institutional Review Board (IRB) 
according to IRB requirements.   
The site must confirm the SAE in appropriate source documents and provide detailed information pertaining to 
the event to the sponsor and reviewing IRB if requested. 
9.3 
Adverse Event Severity 
The Investigator will be asked to characterize the severity of each AE as mild, moderate or severe.  The 
assessment is subjective and the Investigator will use medical judgment to compare the reported AE to similar 
types of events observed in clinical practice.  Guidelines for AE severity assessment are as follows: 
Mild:  The AE is transient and easily tolerated by the subject. No medical treatment required. 
Moderate:  The AE causes the subject discomfort and interrupts the subject’s usual activities. Medical 
treatment required to alleviate or lessen the impact of this untoward condition. 
Severe:  The AE causes considerable interference with the subject’s usual activities may be incapacitating 
and may require hospitalization.  See Section 9.1.3 Serious Adverse Events. 
9.4 
Adverse Event Association 
The relationship of all AEs to the device, the procedure or general surgery will be classified by the Investigator as 
not related, possibly related, probably related or definitely related. 
Not related: The AE is due to an underlying or concurrent illness or effect of another device, drug or 
intervention and is not related to the study device, procedure or general surgery. 
Possibly related: The causal and/or temporal relationship to the study device, procedure or general surgery, 
is equally or less likely than other plausible explanations. 
Probably related: The causal and/or temporal relationship to the study device, procedure or general surgery, 
is likely or significantly more likely than other plausible explanations. 
Definitely related: A clinical event that can only be attributed to the device, procedure or general surgery. 
9.5 
Potential Risks and Anticipated Adverse Events 
9.5.1 
General Surgery Risks 
General surgical risks are but may not be limited to: 
• 
Airway obstruction  
• 
Anaphylaxis 

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• 
Anesthesia related 
• 
Atelectasis 
• 
Blood clots, including pulmonary emboli 
• 
Cardiac arrest 
• 
Cardiac, other 
• 
CVA 
• 
Death 
• 
Decompensation  
• 
Deep vein thrombosis 
• 
Epidural fibrosis 
• 
Epidural hematoma or bleeding 
• 
Excessive blood loss 
• 
Hemorrhage, possibly requiring blood 
transfusion 
• 
Infection, deep wound 
• 
Infection, superficial wound 
• 
Infection, urinary tract 
• 
Infection, other 
• 
Myocardial infarction 
• 
Phlebitis 
• 
Pleural effusion 
• 
Pneumonia 
• 
Pneumothorax 
• 
Poor tissue healing 
• 
Retained sponge 
• 
Septicemia 
• 
Suture abscess 
• 
Transfusion reaction 
• 
Vascular or blood vessel injury 
• 
Wound dehiscence 
9.5.2 
Posterior Fusion Surgery Risks 
Posterior Fusion surgical risks are but may not be limited to: 
• 
Allergic reaction to the implant/retractor 
materials 
• 
Bowel and bladder dysfunction 
• 
Disc height loss 
• 
Dural tear, with or without CSF leak 
• 
Dysesthesia or numbness 
• 
Erosion due to implant 
• 
Failure to relieve symptoms including 
unresolved pain 
• 
Foreign body reaction 
• 
Kyphosis or hyperextension 
• 
Loss of spine flexibility 
• 
Muscle and tissue injury or damage 
• 
Nerve injury 
• 
Nerve root injury 
• 
Osteolysis 
• 
Pain, new onset 
• 
Pain, unresolved 
• 
Paralysis 
• 
Pseudoarthrosis 
• 
Sexual dysfunction 
• 
Spinal cord damage 
• 
Spinal degradation 
• 
Spinous process fracture 
• 
Surgical intervention at incorrect level 
• 
Thigh pain 
• 
Tingling 
• 
Vertebral body fracture 
• 
Weakness 
9.5.3 
K2M Device Risks 
Risks specific to the VESUVIUS Demineralized Fibers and EVEREST system are but may not be limited to: 
• 
Bone graft migration 
• 
Bone graft subsidence 
• 
Device instability 
• 
Device malposition 
• 
Device migration 
• 
Device subsidence 
• 
Disengagement – from bone 
• 
Disengagement – screw/rod interface 
• 
Foreign body reaction 
• 
Hook/rod interface disengagement 
• 
Material degradation 
• 
Prominent implants 
• 
Rod breakage 
• 
Screw back-out 
• 
Screw breakage 
• 
Screw/rod interface slide 
• 
Set screw loosening 
 
 
 
 
 

 
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10 SITE REGULATORY REQUIREMENTS 
10.1 Institutional Review Board (IRB) Approval 
Prior to enrolling subjects in the study, site IRB approval must be obtained according to 21 CFR Part 56.  IRB 
approval must be maintained by the site throughout the study.  The IRB approval letter(s) must be maintained 
in the study files at all times. 
10.2 Study Specific Informed Consent 
A study specific sample informed consent will be provided to each site prior to the IRB process.  The sample 
informed consent should be used as a template for creating the IRB specific informed consent.  Prior to 
submission of the proposed informed consent to the reviewing IRB, the Sponsor must review the informed 
consent for completeness according to the protocol and according to 21 CFR Part 50.  Potential study subjects 
should be offered informed consent according to the process outlined in Section 8.1, Patient Screening and 
Enrollment.   
Patients must not be offered informed consent until written proof of IRB approval is attained.  The patient should 
be given the opportunity to take home a copy of the informed consent to review and discuss with family members 
or acquaintances prior to signing.  Potential study subjects must also be given the opportunity to discuss the 
procedure, risks, benefits, alternative treatments and study requirements prior to signing the informed consent.  
Patients should be informed that they are free to refuse participation in this study and refusal will not affect their 
medical treatment.  If patients elect to participate, it should be made clear that they may withdraw from the study 
for any reason and at any time without prejudicing further care. 
A copy of the signed and dated IRB approved informed consent should be given to all subjects. 
10.3 Regulatory Documents 
Prior to patient enrollment, the following documents must be provided to the Sponsor and be on file at the site: 
• 
Curriculum vitae and copy of medical license for Principal and Sub-Investigators 
• 
IRB approval letter and IRB roster  
• 
IRB approved Informed Consent Form 
• 
Signed Clinical Research Agreement 
• 
Signed Investigators agreement for Principal and Sub-Investigators, as required 
• 
Finalized budget agreement 
• 
Financial disclosures for the Principal and Sub-Investigators 
• 
Site Initiation documentation 

 
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11 SITE VISIT/MONITORING PROCEDURES 
Monitoring of the study will be a continuous process conducted in accordance with 21 CFR 812.46 and 
applicable Sponsor procedures.  Monitoring will be performed by qualified clinical research personnel, or 
designees, of K2M.   
11.1 Site Qualification Visit 
Prior to selecting an Investigator for participation in the study a Qualification visit will be performed.  The purpose 
of the visit is to confirm that the Investigator/investigative site has adequate staff, including a designated Study 
Coordinator, and facilities to perform the study according to the requirements of the protocol. 
11.2 Study Initiation Visit 
Prior to enrolling subjects at a study site, a Site Initiation Visit will be performed. The purpose of the visit is to 
confirm that the site continues to be qualified for participation and to review the Investigator/site responsibilities 
and requirements for the study.  Site training will be performed and will include: 
• 
Review of the clinical protocol and data collection process 
• 
Monitoring requirements 
• 
IRB requirements 
• 
Informed Consent process 
• 
Review of site records 
11.3 Periodic Monitoring Visits  
Periodic site monitoring visits will be performed during the study by a designated study monitor assigned by the 
Sponsor.  The purposes of the visits are to confirm compliance to the protocol, review regulatory documents, 
accurate and complete records are being maintained and to compare source documents to completed CRFs 
for completeness and consistency.  The initial monitoring visit to a site will be scheduled soon after the first 2 to 
5 patients are enrolled in the study and may occur prior to the first surgery.  The frequency of subsequent visits 
will be dependent upon the rate of enrollment and site performance on previous monitoring visits.  If possible, 
monitoring visits will be performed at least quarterly.  Specific assessments during a monitoring visit include: 
• 
Continued site acceptability 
• 
Compliance to the protocol 
• 
IRB approval status 
• 
Use of the approved informed consent 
• 
Adequacy of source documents 
• 
Complete and accurate CRFs 
• 
Reporting of adverse events 
• 
Protocol deviations 
• 
Site records 
If it is determined during a monitoring visit that there are significant non-compliance issues at a site, including 
adherence to the protocol or applicable regulatory requirements, the issues will be discussed with the 
Investigator and Study Coordinator and the site will be instructed how to gain compliance.  If continued non-
compliance is detected on a subsequent monitoring visit, it may be necessary to terminate site participation in 
the study. 
11.4 Final Close-Out Visit 
At the completion of the last long-term follow-up visit at each site a final close-out visit will be performed.  The 
purpose of the visit will be to: 
• 
Reconcile all outstanding data queries 
• 
Review site records 
• 
Review the records retention requirements for the study 
• 
Review the final IRB requirements for the study 

 
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12 STATISTICAL METHODS 
12.1 Study Design 
Prospective, single arm, multi-center study with historical controls to evaluate radiographic and clinical outcome 
variables of the VESUVIUS Demineralized Fibers and the EVEREST Spinal System compared to literature 
reported outcomes for patients with spinal stenosis, spondylolisthesis, and/or degenerative disc disease treated 
using traditional autograft with posterior stabilization. Subjects undergoing fusion with the VESUVIUS 
Demineralized Fibers and the EVEREST Spinal System may also receive an interbody spacer (using the TLIF 
technique) based on the physician’s standard of care. 
12.2 Study Hypotheses  
The primary study endpoint is the rate of fusion at 24 months.  The primary hypothesis of this trial is that the 
fusion rate with the VESUVIUS Demineralized Fibers and the EVEREST Spinal System combination is non-
inferior to the fusion rate achieved and reported with the traditional fusion utilizing autograft and posterior 
stabilization.  
A PubMed literature review was conducted to assemble relevant publications utilizing results from posterior 
fusion surgeries incorporating osteobiologics. Searches included all peer-reviewed journals published between 
January 2000 and April 2013. Sample sizes, patient populations, evaluated variables, results, and recorded 
complications were assessed for each selected article. Only articles describing the use of autograft in 
comparable patient populations were incorporated into the results. The following table gives the fusion rates 
found during the literature review: 
 
Papers* 
Number of 
Cases 
Number of 
Fusions 
Fusion 
Rate 
Paper 11 
Paper 2A2 
Paper 2B 
Paper 33 
Paper 44 
Paper 5A5 
Paper 5B 
Paper 6A6 
Paper 6B 
Paper 7A7 
Paper 7B 
Paper 8A8 
Paper 8B 
81 
39 
35 
36 
45 
21 
22 
10 
10 
47 
48 
42 
42 
44 
34 
29 
15 
33 
19 
20 
10 
10 
44 
42 
31 
24 
54.3% 
87.2% 
82.9% 
41.7% 
73.3% 
90.5% 
90.9% 
100.0% 
100.0% 
93.6% 
87.5% 
73.8% 
57.1% 
Pooled 
478 
355 
74.3% 
  
 
 
* Refer to Appendix 2 for references 
A total of 355 successes in 478 subjects gives an overall fusion rate of 74.3%. The hypotheses to be tested for 
this primary endpoint are as follows: 
HO:  PK2M ≤ P0 - δ 
HA:  PK2M> P0 - δ 
  
where PK2M is the success rate of the VESUVIUS Demineralized Fibers and the EVEREST Spinal System 
combination, P0 is the literature success rate of 74.3% and δ is the non-inferiority margin of 10% against the 
historical success rate. 
 

 
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12.3 Sample Size 
A total sample size of 204 was selected for the study.   Assuming the actual fusion success rate of the 
VESUVIUS Demineralized Fibers and the EVEREST Spinal System combination is the same as the historical 
rate (74.3%) and using a one-sided 0.05 exact binomial test to evaluate the hypothesis in section 12.2 (H0: PK2M 
≤ 0.643), a sample size of 173 provides >80% power.  To account for 15% drop out, one will need a sample 
size of 172. However, the sample size was increased to 204 to account for safety considerations.  A sample 
size of 204 provides >80% power to see at least one serious adverse event that occurs in 0.8% of the population 
and 87% power to see a serious adverse event that occurs in 1.0% of the population.  Thus, a sample size of 
204 provides reasonable assurance that an uncommon serious adverse event would be seen in the study should 
one exist. 
   
Subject enrollment will be capped so that no single site contributes more than approximately 15% of the cases. 
12.4 Analysis Populations 
Analysis Populations are defined as follows: 
• 
The Intent-to-Treat (ITT) population includes all enrolled subjects. 
• 
The Per-Protocol population includes all enrolled subjects who have no major protocol violations 
(defined as not meeting inclusion/exclusion criteria or not being consented properly).   
 
The fusion analysis will be performed on the ITT population. Analysis of the per-protocol population will be 
confirmatory of the ITT analysis. The safety analysis will be performed on the ITT population.   
12.5 Analysis of Primary Endpoint 
The primary study endpoint will be evaluated by a one-sided exact test of the VESUVIUS Demineralized Fibers 
and the EVEREST Spinal System combination success rate against the literature success rate of 74.3% with a 
non-inferiority margin of 10% at a significance level of 0.05. If the lower bound to the exact one-sided 95% 
Confidence Interval of the VESUVIUS Demineralized Fibers and the EVEREST Spinal System combination 
success rate is greater than 64.3%, the primary endpoint will have been met.  
12.6 Safety Analyses 
Incidence rates of adverse events will be provided descriptively in tabular form for each study groups for the 
overall adverse event rate, serious adverse event rates, revision rates, removal rates, etc. at each follow-up 
interval. 
12.7 Supplementary Analysis 
Other ancillary variables such as demographics, baseline variables, surgical variables and post-op pain 
medication usage will be summarized by mean, standard deviation, median (if appropriate), and range for 
continuous measures, and frequency and percent for categorical measures.  Descriptive statistics and graphical 
methods such as bar graphs, box and whiskers plots, and star plots may be employed to compare subjects’ 
clinical outcomes to baseline values (pre-operative) and the prospective and historical study groups 
simultaneously for multiple variables.  
Descriptive statistics or graphical methods will also be used to explore the impact of any covariates of interest, 
e.g., presence or absence of anterior spacer on the prospectively collected outcome data. 
12.8 Methods to Minimize Bias 
This trial includes several well-validated patient-reported outcome measures (i.e., ODI, VAS, and SF-12v2).  
When providing follow-up self-reports of these outcomes, subjects will remain blinded to their previous 
responses on these instruments so as to not bias their current reports.  With respect to the SF-12v2, previously 
published validation studies have shown that the results of this instrument, particularly the physical functioning 
domains, are not substantially affected by non-specific study effects such as placebo.  When conducting follow-
up neurological examinations, every effort will be made to blind the investigators to the ratings provided at earlier 

 
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intervals. Investigational sites will be restricted from enrolling more than approximately 15% of the study cohort. 
Radiographic evaluations will be conducted by an independent central radiologist. 
We will evaluate the subjects from each site to assess poolability of the data.  Sites will be examined for 
adherence to the requirements of the protocol, baseline demographic and relevant clinical characteristics. 

 
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13 SITE RESPONSIBILITIES 
13.1 Investigator  
Principal Investigators selected by K2M to participate in this clinical study assume overall responsibility for the 
performance of the study at the site. 
Specifically, the Investigator will assume the overall responsibility for: 
• 
Obtaining IRB approval 
• 
Conducting the study according to the clinical protocol and applicable, federal, state and local 
regulations and the signed Clinical Research Agreement 
• 
Providing financial disclosure according to federal regulations 
• 
Proper execution of the approved informed consent 
• 
Protecting the rights, safety and welfare of study subjects 
• 
Appropriate source documents to verify study data 
• 
Reviewing and signing all CRFs for subjects enrolled in the study 
• 
Oversight and training of site staff given study related responsibilities 
13.2 Study Coordinator 
The Study Coordinator is designated by the Investigator to assume site management responsibilities.  
Specifically, the Study Coordinator is responsible for: 
• 
Managing the IRB submission and approval process 
• 
Managing study activities according to the clinical protocol and applicable, federal, state and local 
regulations and the signed Clinical Research Agreement 
• 
Ensuring proper execution of the approved informed consent 
• 
Protecting the rights, safety and welfare of study subjects 
• 
Maintaining appropriate source documents to verify study data 
• 
Ensuring that CRFs are complete, reviewed and signed by the Investigator at the completion of 
patient contacts and before scheduled monitoring visits  
• 
Management of additional staff members given study related responsibilities 
If the Investigator designates a replacement Study Coordinator at any time during the performance of the study, 
the Sponsor must be notified immediately.  A Sponsor designee will arrange to visit the site as soon after the 
notification as is feasible to ensure that the replacement Study Coordinator has the ability and is adequately 
trained to function in that capacity. 
 

 
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14 RECORDS AND REPORTS 
All Sponsor and site records may be subject to regulatory inspection and must be retained for a period of 2 
years following, a) the date the investigation is completed or terminated, or b) the records are no longer required 
to support a regulatory submission, whichever is longer.  The Sponsor will notify the site in regard to length of 
record retention at the completion of the study. 
14.1 Investigator/Site Records 
Investigator/site records must be maintained and updated as necessary.  Records will be reviewed during the 
site initiation visit and on subsequent monitoring visits to ensure adequacy and completeness of records.  
Investigator/site records include, but may not be limited to: 
• 
Original and all subsequent IRB approval letters 
• 
Original and all subsequent (if applicable) approved informed consents 
• 
IRB Roster 
• 
IRB updates/reports as required by reviewing IRB 
• 
Final protocol and subsequent (if applicable) protocol amendments 
• 
Other required reports 
• 
Relevant correspondence between the Investigator, IRB and K2M  
• 
Signed Clinical Research Agreement 
• 
Investigators Agreement for Principal and Sub-Investigators, as required 
• 
Financial Disclosure Documents 
• 
Copies of Curriculum Vitae for the Investigator and Sub-Investigators 
• 
Site Signature & Responsibility Log 
• 
Site Monitoring Log 
• 
Signed Informed Consents 
• 
Completed Case Report Forms 
14.2 Investigator/Site Reports 
The Investigator/site is responsible for the preparation and submission of reports to the Sponsor, IRB and 
applicable Regulatory agencies.  The following reports are required: 
Serious Adverse Events: Submitted to the Sponsor within 10 working days of first learning of the event 
and to the reviewing IRB as required 
Withdrawal of IRB approval: Sponsor must be notified within 5 working days   
IRB Updates/Reports: Submitted to the reviewing IRB as required 
Failure to Obtain Informed Consent: Submitted to the Sponsor and reviewing IRB within 5 working days 
after realizing the failure  
Final Report: Submitted as required to the reviewing IRB 
 
 

 
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14.3 Sponsor Records 
The Sponsor will maintain site specific study files including: 
• 
Copy of the original and all subsequent IRB approval letters 
• 
Copy of the original and all subsequent (if applicable) approved informed consents 
• 
IRB Roster 
• 
Copy of IRB updates/reports as required by reviewing IRB 
• 
Other required reports 
• 
Relevant correspondence between the Investigator, IRB and K2M 
• 
Signed Clinical Research Agreement 
• 
Investigators Agreement for Principal and Sub-Investigators, as required 
• 
Clinical Research Agreement and Investigators Agreement template, as applicable 
• 
Financial Disclosure Documents 
• 
Copies of Curriculum Vitae for the Investigator and Sub-Investigators 
• 
Copies of site approved recruitment and patient information documents 
• 
Site Initiation Report 
• 
Site Monitoring Reports 
• 
Completed Case Report Forms 
In addition, the Sponsor will maintain a Study Central File including, but not limited to: 
• 
Final protocol and subsequent (if applicable) protocol amendments 
• 
Investigator agreement template 
• 
Master recruitment and patient information documents (if applicable) 
• 
Composite listing of adverse events 
• 
Data and data analysis 
• 
Interim (if applicable) and final summary 
14.4 Sponsor Reports 
The Sponsor is responsible for the preparation and submission of reports to the site and applicable Regulatory 
agencies.  The following reports are required: 
Serious Adverse Events: Submitted to the FDA only if they meet the requirements for MDR reporting 
Final Report: Submitted to all sites upon completion of the study and final data analysis 
Reports not listed may be made by the Sponsor to Regulatory agencies and to the sites if additional notifications 
are necessary. 
 
 
 
 

 
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15 PUBLICATION POLICY 
Data resulting from the conduct of this study are considered confidential information.  Abstracts, book chapters, 
peer-reviewed manuscripts and other publications (all of which are “Publications”) resulting from the study can 
originate from the Sponsor or from Investigators participating in the study; provided, however, any Publications 
shall be governed by and in compliance with the terms of Section VIII of the Clinical Evaluation Research 
Agreement. 
 
 

 
Rev 1 March 3, 2015 
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APPENDIX 1 – Bone Marrow Aspiration & Hydration of VESUVIUS Demineralized 
Fibers 
NOTE:  VESUVIUS Fibers are packaged in quantities of 2, 5, 15, and 30 cc; use this to help estimate the volume of 
local bone used 
 
Bone marrow aspiration from the posterior or anterior iliac crest is performed as follows: 
1. Locate site for aspiration of bone marrow. 
2. Using sterile technique, prepare surgical site and anesthetize the area. 
3. With a scalpel, make incision in the skin above the area from which the bone marrow is to be 
aspirated. 
4. Hold needle with proximal end in palm and index finger against the shaft near the tip.  This position 
stabilizes the needle and enhances needle control. 
5. Introduce needle through prepared incision site. 
6. Use gentle, but firm pressure to advance the needle.  Rotate needle in alternating clockwise-
counterclockwise motion, or gently tap the needle handle with a mallet.  In general, decreased 
resistance is encountered upon entrance into the marrow cavity. 
7. Remove stylet by rotating upper section of handle and pulling stylet straight out. 
8. Screw the distal end of the included syringe into the proximal hub of the bone-marrow aspiration 
needle.  Ensure a firm fit, but do not over-tighten. 
9. Apply suction by withdrawing syringe plunger to draw bone marrow asparite (BMA) into the syringe.  
NOTE: If using a multi-fenestrated bone-marrow aspiration needle, withdraw no more than 10ml BMA 
from each harvest site.  If using a non-fenestrated bone-marrow aspiration needle, withdraw no more 
than 2ml BMA from each harvest site. 
10. VESUVIUS Demineralized Fibers graft material and BMA should be combined in a 3:2 volumetric 
ratio (approximately 15cc Fibers and 10ml BMA required for a one-level case).  Supplement the BMA 
with venous-line blood if BMA volumes are insufficient to achieve a 3:2 ratio.  NOTE:  A 1:1 ratio of 
Fibers:BMA tends to yield an overly wetted final graft construct.  This mixture is added to extend local 
bone for grafting. 
11. Disengage syringe containing the aspirated bone marrow and immediately transfer the aspirated 
bone marrow from the syringe onto the VESUVIUS Demineralized Fibers.  Dispose of the needle in 
accordance with applicable laws and regulations. 
 
Marrow aspiration from the vertebral body is performed as follows: 
1. Access the vertebral body via transpedicular technique. 
2. Use gentle, but firm pressure to advance the needle through the pedicle into the vertebral body.  
Rotate needle in alternating clockwise-counterclockwise motion, or gently tap the needle handle with 
a mallet.  In general, decreased resistance is encountered upon entrance into the marrow cavity. 
3. Remove stylet by rotating upper section of handle and pulling stylet straight out. 
4. Screw the distal end of the included syringe into the proximal hub of the bone-marrow aspiration 
needle.  Ensure a firm fit, but do not over-tighten. 
5. Apply suction by withdrawing syringe plunger to draw bone marrow aspirate (BMA) into the syringe.  
NOTE: If using a multi-fenestrated bone-marrow aspiration needle, withdraw up to 8ml BMA from 
each pedicle (16ml total from each vertebral body).  If using a non-fenestrated bone-marrow 
aspiration needle, eight discrete 2ml aspirations can be harvested from each vertebral level – four 

 
Rev 1 March 3, 2015 
CONFIDENTIAL 
Page 37 of 38 
from the right and four from the left pedicle, using a coaxial transpedicular technique.  Collect 
aspirates from each of four vertebral depths, one at the superficial depth just beyond the origin of the 
pedicle from the back of the vertebral body (30mm) and the others from the subsequent depths of 
35mm, 40mm, and 45mm of cannula insertion.  This technique will yield up to 16ml of bone-marrow 
aspirate from each vertebral body. 
6. VESUVIUS Demineralized Fibers graft material and BMA should be combined in a 3:2 volumetric 
ratio (approximately 15cc Fibers and 10ml BMA required for a one-level case).  Supplement the BMA 
with venous-line blood if BMA volumes are insufficient to achieve a 3:2 ratio.  NOTE:  A 1:1 ratio of 
Fibers:BMA tends to yield an overly wetted final graft construct.   This mixture is added to extend 
local bone for grafting. 
7. Disengage syringe containing the aspirated bone marrow and immediately transfer the aspirated 
bone marrow from the syringe onto the VESUVIUS Demineralized Fibers.  Dispose of the needle in 
accordance with applicable laws and regulations. 
 
 

 
Rev 1 March 3, 2015 
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APPENDIX 2 – SAP References 
 
1 Cammisa FP Jr, Lowery G, Garfin SR, Geisler FH, Klara PM, McGuire RA, Sassard WR, Stubbs H, Block 
JE. “Two-year fusion rate equivalency between Grafton DBM gel and autograft in posterolateral spine 
fusion: a prospective controlled trial employing a side-by-side comparison in the same patient.” Spine 
(Phila Pa 1976). 2004 Mar 15; 29(6):660-6. 
 
2 Chen WJ, Tsai TT, Chen LH, Niu CC, Lai PL, Fu TS, McCarthy K. “The fusion rate of calcium sulfate with 
local autograft bone compared with autologous iliac bone graft for instrumented short-segment spinal 
fusion.” Spine (Phila Pa 1976). 2005 Oct 15; 30(20):2293-7. 
 
 
3 Glassman SD, Dimar JR, Carreon LY, Campbell MJ, Puno RM, Johnson JR. “Initial fusion rates with 
recombinant human bone morphogenetic protein-2/compression resistant matrix and a 
hydroxyapatite and tricalcium phosphate/collagen carrier in posterolateral spinal fusion.” Spine (Phila 
Pa 1976). 2005 Aug 1; 30(15):1694-8. 
 
4 Dimar JR, Glassman SD, Burkus KJ, Carreon LY. “Clinical outcomes and fusion success at 2 years of 
single-level instrumented posterolateral fusions with recombinant human bone morphogenetic 
protein-2/compression resistant matrix versus iliac crest bone graft.” Spine (Phila Pa 1976). 2006 Oct 
15;31(22):2534-9; discussion 2540. 
 
5 Niu CC, Tsai TT, Fu TS, Lai PL, Chen LH, Chen WJ. “A comparison of posterolateral lumbar fusion 
comparing autograft, autogenous laminectomy bone with bone marrow aspirate, and calcium 
sulphate with bone marrow aspirate: a prospective randomized study.” Spine (Phila Pa 1976). 2009 
Dec 1;34(25):2715-9. doi: 10.1097/BRS.0b013e3181b47232. 
 
6 Taghavi CE, Lee KB, Keorochana G, Tzeng ST, Yoo JH, Wang JC. “Bone morphogenetic protein-2 and 
bone marrow aspirate with allograft as alternatives to autograft in instrumented revision posterolateral 
lumbar spinal fusion: a minimum two-year follow-up study.” Spine (Phila Pa 1976). 2010 May 
15;35(11):1144-50. doi: 10.1097/BRS.0b013e3181bb5203. 
 
7 Hoy K, Bünger C, Niederman B, Helmig P, Hansen ES, Li H, Andersen T.  “Transforaminal lumbar interbody 
fusion (TLIF) versus posterolateral instrumented fusion (PLF) in degenerative lumbar disorders:  a 
randomized clinical trial with 2-year follow-up.”  Eur Spine J, 2013 22:2022-2029. 
 
8 Kong S, Park JH, Roh SW.  “A prospective comparative study of radiological outcomes after instrumented 
posterolateral fusion mass using autologous local bone or a mixture of beta-tcp and autologous local 
bone in the same patient.”  Acta Neurochir.  2013 155:765-770.