Lumbar Fusion With 3D-Printed Porous Titanium Interbody Cages - A Single-Blinded Randomized Controlled Trial Evaluating Nexxt Matrixx(TM) Versus PEEK Cages
Phase: NA
Conditions: Lumbar Degenerative Disc Disease, Lumbar Spinal Stenosis, Lumbar Spondylolisthesis, Lumbar Spinal Deformity, Lumbar Spondylosis
Sponsor: Ohio State University

 
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Lumbar Fusion with 3D-Printed Porous Titanium Interbody Cages –  
A Single-Blinded Randomized Controlled Trial Evaluating Nexxt MatrixxTM Versus 
PEEK Cages 
 
NCT03647501 
 
07/09/2021 
 
 
 
 
 
 
 
 
 
V2 
 
 
 
 
 
 
 
SPONSOR 
 
 
 
 
 
 
 
 
 
 
 

 
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SIGNATURE PAGE 
 
 
 
TITLE:  Lumbar Fusion with 3D-Printed Porous Titanium Interbody Cages –  
A Single-Blinded Randomized Controlled Trial Evaluating Nexxt MatrixxTM Versus PEEK 
Cages 
 
 
Protocol Number:  
Date:  
 
The signatures of the investigator and representative of the sponsor below constitute their 
approval of this protocol and provide the necessary assurances that this Clinical Trial will 
be conducted according to Good Clinical Practices and to all stipulations, clinically and 
administratively, as stated in the protocol, including all statements as to confidentiality. 
It is agreed that the protocol contains all necessary information required to conduct the 
Clinical Trial as outlined in the protocol.  
It is agreed that all participants in this study will provide written informed consent and/or 
a HIPAA Authorization and agree to the Clinical Trial procedures as approved by the 
Institutional Review Board, as applicable. 
 
SPONSOR: 
 
__________________________________ 
Print Name 
 
__________________________________ 
 
______________________ 
Signature 
 
 
 
 
 
Date 
 
PRINCIPAL INVESTIGATOR: 
 
__________________________________ 
Print Name 
 
__________________________________ 
 
______________________ 
Signature 
 
 
 
 
 
Date 

 
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TABLE OF CONTENTS 
 
 
 
1  
INVESTIGATIONAL PLAN .................................................................................. 4 
1.1  
Purpose ................................................................................................... 4 
2  
INTRODUCTION .................................................................................................. 4 
2.1  
Background .............................................................................................. 4 
2.2  
Device Description ................................................................................... 6 
3  
TRIAL DESIGN .................................................................................................... 7 
3.1  
Design ..................................................................................................... 7 
3.2  
Inclusion Criteria ...................................................................................... 7 
3.3  
Exclusion Criteria ..................................................................................... 8 
4  
STUDY PROCEDURE ......................................................................................... 9 
4.1  
Screening Assessments ........................................................................... 9 
4.1.1  Informed Consent .................................................................................... 9 
4.1.2  Medical History and Demographic Data ................................................ 9 
4.1.3  Pregnancy Screening .............................................................................. 9 
4.1.4  Clinical Assessments ............................................................................ 10 
4.2 
Randomization ....................................................................................... 10 
4.3 
Perioperative and Postoperative Management ....................................... 10 
4.4 
Schedule of Events ................................................................................ 11 
4.5  
Follow-Up Assessments ......................................................................... 11 
4.6 
Independent Radiographic Assessment ................................................. 12 
4.7  
Success Criteria ..................................................................................... 13 
4.7.1  Primary Measure of Effectiveness ....................................................... 13 
4.7.2 Secondary Measure of Effectiveness .................................................. 13 
4.8  
Subject Withdrawal ................................................................................ 13 
5  
COMPLICATIONS ............................................................................................. 14 
5.1  
Definitions .............................................................................................. 14 
6  
STATISTICAL ANALYSIS PLAN ...................................................................... 14 
7  
REFERENCES ................................................................................................... 15 
APPENDIX 1 ................................................................................................................. 17 
Case Report Forms (CRFs) ............................................................................... 17 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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1  
INVESTIGATIONAL PLAN 
 
1.1  
Purpose 
The purpose of this randomized controlled trial is to assess and compare 
radiographic and clinical outcomes in patients who are to undergo combined 
interbody/posterolateral lumbar fusion procedures, supplemented with pedicle 
screw instrumentation, using one of the following interbody cages; the Nexxt Spine 
Nexxt MatrixxTM 3D-printed titanium cage or the HonourTM poly-ether-ether-ketone 
cage.  
 
2  
INTRODUCTION 
 
2.1  
Background 
 
In 2012, over 727,000 spinal fusion and non-fusion procedures were performed in 
the US (Millennium Research Group (MRG), 2013). This included treatment for 
various conditions such as DDD, spinal stenosis, spondylosis, spondylolisthesis, 
spinal deformities, tumors, and traumatic spinal injuries. Over time, intervertebral 
discs wear down and lose water and then disc height. The degeneration of these 
discs can impact the spine in several ways, including spinal canal stenosis, 
spondylolisthesis, and osteophyte and bony growth formation. These changes can 
impinge on the spinal cord and nerve roots, causing chronic pain. Consequently, 
as the older population in the US expands, demand for treatments that address 
back and extremity pain will rise accordingly. The correlation between age and the 
incidence of DDD has been well-documented; for example, one study concluded 
that there was a direct relationship between age and the macroscopic grade of 
degeneration caused by DDD (Quint and Wilke, 2008).  Increasing rates of obesity 
in the US will also likely contribute to growth in spinal fusion and non-fusion 
volumes because obesity represents a risk factor for DDD (Hangai M, et al., 2008).  
 
The premise behind fusion surgery for lower back pain (LBP) and leg pain is that 
a degenerated and mobile lumbar segment acts as a pain generator. 
Consequently, if motion is prohibited through a fusion, it is expected that the patient 
will experience improvement in both pain and disability, which will increase their 
ability to function. Currently, there is no way to be certain which structure or 
structures actually are causing the pain, but the main interest has been focused 
on the facet joints, discs, or a combination of both (Fritzell P et al., 2002). 
 
Lumbar spine fusion rates can vary according to the surgical technique.  Although 
many studies on spinal fusion have been conducted and reported, the 
heterogeneity of the study designs and data handling make it difficult to identify 

 
Page 5 of 17 
 
which approach yields the highest fusion rate. Traditional posterolateral inter 
transverse process fusion (PLF) still remains a good procedure with acceptable 
fusion rates for most degenerative conditions. For solid fusion, PLF can be 
combined with interbody fusion (IF) to circumferentially stabilize the relevant 
segment, even though it is unclear whether this improves the rate of fusion (Lee et 
al, 2011).  
 
A bone graft or bone graft substitute is required to produce the fusion and can be 
implanted on its own, in the posterolateral gutters, or contained with an interbody 
device using either a posterior or anterior approach. Spinal fusion procedures are 
the largest source of bone graft product use. The current gold standard is autograft 
bone, wherein tissue is harvested from the patient, usually from the iliac crest or 
locally, and is then placed over the fusion surfaces. Autograft is the gold standard 
because it possesses all of the characteristics necessary for new bone growth—
namely, osteoconductivity, osteogenicity, and osteoinductivity. Osteoconductivity 
refers to the situation in which the graft supports the attachment of new osteoblasts 
and osteoprogenitor cells, providing an interconnected structure through which 
new cells can migrate and new vessels can form.  Osteogenicity refers to the 
situation when the osteoblasts that are at the site of new bone formation are able 
to produce minerals to calcify the collagen matrix that forms the substrate for new 
bone. Osteoinductivity refers to the ability of a graft to induce nondifferentiated 
stem cells or osteoprogenitor cells to differentiate into osteoblasts (Laurencin C. et 
al., 2006). 
 
The mechanical and structural properties of an interbody device are used to 
support osteogenesis across the interbody space and contribute to the success of 
a spinal fusion procedure. One of the most popular synthetic implant materials is 
poly-ether-ether-ketone (PEEK).  PEEK is used as a spacer between vertebrae 
while providing surfaces allowing for bone formation. While macroscale properties 
such as implant shape contribute to the growth of a fusion mass, microscale 
properties such as implant topography likely play a much larger role through 
facilitating osteoblastic differentiation, osteoid synthesis, and mineralization.  
 
Recent studies have shown that PEEK does not integrate well with the surrounding 
bone and instead may form a fibrous connective interface (Kurtz and Devine, 2007; 
Anjarwalla et al., 2006). Recently, the relative failure of osseo-integration observed 
with PEEK implants has been demonstrated to be associated with the reduced 
ability of cells on the implant surface to generate an environment rich in angiogenic 
factors. In contrast, implants fabricated from titanium result in good bone-to‐
implant contact and are osseo-integrated into the surrounding bone. Osteoblasts 

 
Page 6 of 17 
 
on rough titanium substrates have been shown to produce angiogenic factors 
including significantly higher VEGF-A and FGF‐2 levels on smooth and rough 
titanium alloys than on PEEK, an effect significantly more robust on rough titanium 
alloy (Olivares‐Navarrete et al., 2013).  
 
 
2.2  
Device Description 
 
Subjects enrolled in this study will have either the Nexxt Spine Nexxt MatrixxTM 3D-
printed titanium cage or the HonourTM PEEK cage implanted at each level of 1 or 
2-level lumbar arthrodesis procedures. All constructs will be supplemented with a 
pedicle screw system (Depuy Synthes Expedium) cleared for lumbar spinal fusion.  
 
Nexxt MatrixxTM interbody fusion cages are manufactured with detailed 
specifications utilizing modern 3-D printing technology to replicate the cellular 
structure of cancellous bone. 3-D printing technology allows for the creation of a 
complex lattice geometry that cannot be created by traditional orthopedic 
manufacturing processes. First, a uniform 3-D architecture with a consistent 70% 
porosity provides an optimal biomechanical and biological environment for 
promotion of osseous tissue regeneration throughout implant walls. Second, an 
interconnected array of 300-700μm pores creates ideal an environment for natural 
influx of proteins, hormones, growth factors and mesenchymal stem cells to 
promote osteoinduction. 
 
In a review article by Karageorgiou and colleagues (2005), a noted minimum pore 
size of 100 μm was reported to be more conducive to bone ingrowth than pore 
sizes less than 75 μm. However, the authors recommended pore sizes greater 
than 300 μm as other studies have shown a better osteogenic response. In a 
transcortical rabbit study, titanium alloy (Ti6Al4V) implants with 100, 200, and 300 
μm pores were compared; the larger pore sizes resulted in a higher percentage of 
bone within the pores and a higher percentage of that bone to be lamellar (Götz 
HE et al., 2004). Another study used a 3D-printed Ti6Al4V scaffold implanted over 
the transverse process of goats to study the effects of pore size and porosity on 
osseointegration (Li JP et al., 2007). Five groups of implants having a pore size 
and porosity ranging from 160μm/39% to 680μm/68% were evaluated. While the 
small sample size prevented an evaluation of statistical significance, data trends 
led to the conclusion that the larger pores and porosity allow for greater amounts 
of newly formed bone. Taken together, these studies support the varied porosity 
selection of 300-700μm pore size of the Nexxt Matrixx™ System implants.  
 

 
Page 7 of 17 
 
An additional parameter evaluated is the surface finish (Götz HE et al., 2004). One 
set of the 200μm implants were surface-blasted using an aluminum oxide such 
that a roughness average (Ra) of 7.25μm resulted. The effect of this roughness 
was an increase in the bone-implant contact overall on the surface and within the 
pores. However, a later study (Nakada H. et al, 2007) compared osseointegration 
when alumina and a multiphase calcium phosphate (MCD) were used as the blast 
media. Blasted Ti6Al4V cylinders were implanted into rabbit tibiae and were then 
evaluated two and four weeks after implantation. The histologic results showed the 
MCD to illicit a greater volume of new bone formation. The MCD used in this study 
is the same as the calcium phosphate blast media used in the manufacture of the 
Nexxt Matrixx™ System implants.  
 
The Nexxt Matrixx™ System implants have a roughened surface with a Ra 
measurement ranging from 5.0 to 11.8 that is attained via a calcium phosphate 
surface-blasting process. As stated above, this surface was selected specifically 
due to its capacity for osseointegration. 
 
3  
TRIAL DESIGN 
 
3.1  
Design 
 
The randomized controlled trial will prospectively evaluate the safety and efficacy 
of the Nexxt MatrixxTM System titanium implant supplemented with a pedicle screw 
system as compared to a representative PEEK cage currently used in routine 
fashion for lumbar interbody fusion procedures. This study will capture clinical and 
radiographic outcomes on patients up to 2 years post operatively. Both cages will 
be used in conjunction with milled local autograft bone generated as part of the 
spinal fusion procedure (no iliac crest autograft will be utilized). 
This single centered study will enroll up to 70 subjects (n = 35 per group), with 
subjects followed for a minimum of 12 months post-surgery.  All subjects enrolled 
in the study will be recruited from a pool of subjects eligible for combined 
interbody/posterolateral lumbar fusion surgery. The inclusion/exclusion criteria are 
listed below.   
 
3.2  
Inclusion Criteria 
 
Subjects will be considered for inclusion in this trial if they satisfy the following 
criteria. 
 

 
Page 8 of 17 
 
1. Subject is scheduled to undergo combined interbody and posterolateral spinal 
fusion surgery using either the Nexxt MatrixxTM 3D-printed titanium cage or 
HonourTM PEEK cage in conjunction with local autograft bone, and 
supplementation with a pedicle screw system. 
2. Subject must be over the age of 18 years old. 
3. Subject has been unresponsive to conservative care for a minimum of 6 
months. 
4. The subject must in the investigator’s opinion, be psychosocially, mentally, 
and physically able to fully comply with this protocol including the required 
follow-up visits, the filling out of required forms, and have the ability to 
understand and give written informed consent. 
 
3.3  
Exclusion Criteria 
 
Subjects will be excluded from this trial if they satisfy any of the following criteria: 
 
1. Subjects with previous lumbar arthrodesis surgery. 
2. Subjects requiring additional bone grafting materials other than local autograft 
bone. 
3. Subject has inadequate tissue coverage over the operative site. 
4. Subject has an open wound local to the operative area, or rapid joint disease, 
bone absorption, or osteoporosis. 
5. Subject has a condition requiring medications that may interfere with bone or 
soft 
tissue 
healing 
(i.e., 
oral 
or 
parenteral 
glucocorticoids, 
immunosuppressives, methotrexate, etc.). 
6. Subject has an active local or systemic infection. 
7. Subject has a metal sensitivity/foreign body sensitivity. 
8. Subject is morbidly obese, defined as a body mass index (BMI) greater than 
40. 
9. Subject has any medical condition or extenuating circumstance that, in the 
opinion of the investigator, would preclude participation in the study. 
10. Subject is currently involved in another investigational drug or device study that 
could confound study data. 
11. Subject has a history (present or past) of substance abuse (recreational drugs, 
prescription drugs or alcohol) that in the investigator’s opinion may interfere 
with protocol assessments and/or with the subject’s ability to complete the 
protocol required follow-up.  
12. Subjects who are pregnant or plan to become pregnant in the next 12 months 
or who are lactating. 

 
Page 9 of 17 
 
13. Subject is involved in or planning to engage in litigation or receiving Worker’s 
Compensation related to neck or back pain. 
14. Subject is a prisoner. 
 
4  
STUDY PROCEDURE 
 
4.1  
Screening Assessments 
4.1.1  Informed Consent 
Subjects will be provided with an informed consent and will be given ample 
opportunity to review the consent and ask questions. The signed informed consent 
will be obtained before any study specific procedures, that are not part of the 
investigator’s standard of care begin. A copy of the informed consent will be given 
to the subject. All subjects who meet all of the entry criteria will be considered for 
inclusion in this trial. Any subject meeting any of the exclusion criteria will be 
excluded from the trial. 
All subjects who have agreed to participate in this study, have signed the informed 
consent and who meet the inclusion/exclusion criteria will be considered enrolled 
and assigned a subject ID number. Once a Subject ID number has been issued, it 
cannot be reassigned or used for another subject. 
4.1.2  Medical History and Demographic Data  
Within 60 days prior to the surgery date, the following information will be collected: 
• Demographic data 
• Medical history, including a complete history of spinal disorder(s) (non-
operative or operative treatments performed) 
• Physical examination (including height, weight) 
• X-Rays 
• Current pain medications and other drug therapies. 
• Neurological status - All subjects’ neurological status will be assessed and 
recorded as intact or not intact, based upon the investigator’s motor, 
sensory and reflex evaluations. 
 
4.1.3  Pregnancy Screening 
A pregnancy test will be performed and negative results shall be kept on file for all 
female subjects unless infertile or post-menopausal to ensure subjects are not 
enrolled into the study who are pregnant. 

 
Page 10 of 17 
 
4.1.4  Clinical Assessments 
Subject study data will be collected preoperatively, intra-operatively and 
postoperatively at 3, 6, 12, and when available 24 months.  The following data will 
be recorded on the Case Report Forms (CRFs) and in addition, electronic data 
entry will be employed via an Internet connection when possible using the 
Research Electronic Data Capture (REDCap) program. 
 
Oswestry Disability Index version 2.1a (ODI v2.1a):  Pre-operatively the subject 
will complete the Oswestry Disability Index for a baseline low back pain and 
function assessment.  The questionnaire is a combined pain and function index 
which will be used to assess the subject’s back pain and how that pain affects the 
subject’s ability to manage in everyday life.  The questionnaire is divided into ten 
sections designed to assess limitations of various activities of daily living. Each 
section contains six statements and each statement describes a greater degree of 
difficulty in that activity than the preceding statement. The subject marks the one 
statement in each section, which describes his/her limitations most accurately. 
Each section is scored on a 0-5 scale, 5 representing the greatest disability. The 
scores for all sections are added together, giving a possible score of 50.  The total 
is doubled and expressed as a percentage. If a subject marks two statements, the 
highest scoring statement is recorded as a true indication of his disability. If a 
section is not completed because it is inapplicable, the final score is adjusted to 
obtain a percentage.  
 
Back and Radicular Leg Pain:  Preoperatively all subjects will assess their back 
and/or radicular leg pain in one or both legs using a visual analog scale (VAS) from 
0 - 10 with 10 being considered most painful.  
 
4.2 
Randomization 
 
All subjects will be randomized in the trial to receive either the Nexxt Spine Nexxt 
MatrixxTM 3D-printed titanium cage or the HonourTM PEEK cage supplemented 
with a pedicle screw system and milled local autograft bone. Subject randomization 
will be stratified according to smoking status. Subjects will be blinded to their group 
status for the duration of the study assessments and procedures (12 months post-
operatively).  
 
4.3 
Perioperative and Postoperative Management 
 
Surgeons will perform combined interbody and posterolateral lumbar fusion 
utilizing either Nexxt MatrixxTM or PEEK cages supplemented with a pedicle screw 
system cleared for fusion and milled local autograft bone (per customary protocol).  

 
Page 11 of 17 
 
Data will be collected during and immediately after the surgery according to the 
parameters described by the Nexxt MatrixxTM IF/PLF CRFs.  This includes: 
diagnosis, duration of surgery, blood loss, OR time, length of hospital stay, 
instrumentation used, type of procedure, and surgical level(s).  In addition, all intra-
operative complications (e.g. excessive blood loss, hematoma, vascular injury, 
etc.) will be reported and recorded as a complication on the CRF. 
Intra-operative (after hardware installation is completed) or immediate post-
operative x-rays will be obtained. Postoperative care will follow the standard of 
care at each institution for subjects who undergo fusion procedures. 
 
Postoperative care is extremely important.  The subject should be warned that 
noncompliance with postoperative instructions could lead to breakage of the 
pedicle screw system and/or possible migration requiring revision surgery to 
remove the pedicle screw system.  
 
4.4 
Schedule of Events 
 
 
 
Screening/
Enrollment  
(-60 days of 
procedure) 
Procedure 
3 months  
(± 7 days) 
6 months  
(± 14 days) 
12 months 
(± 30 days) 
24 months 
(± 60 days) 
Informed consent 
X 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Concomitant medications review 
X 
X 
X 
X 
X 
X** 
Randomization 
 
X 
 
 
 
 
Oswestry Disability Index v2.1a 
X 
 
X 
X 
X 
X** 
Visual Analog Scale (VAS) back and 
leg 
X 
 
X 
X 
X 
X** 
Radiographic X-rays (AP/ Lateral with 
Flexion and Extension) 
X 
 
X 
X 
X 
X** 
CT Scan 
 
 
 
X* 
 
 
AE/ SAE review 
X 
X 
X 
X 
X 
X** 
*A CT scan post-op is standard of care in clinical practice to document fusion. The CT scan will be done at 6 
months post-op rather than the usual 12 months. Cost will be covered by study sponsor. **Optional time point (when 
available). 
 
 
 
4.5  
Follow-Up Assessments 
 
Subjects will be asked to return postoperatively at 3 months (± 1 week), 6 months 
(± 2 weeks), and 12 months (± 1 month) for a clinical and radiographic exam. An 
additional visit at 24 months may be scheduled at the request of either the 
physician or the subject. The following data will be recorded on the Case Report 

 
Page 12 of 17 
 
Forms (CRFs) and in addition, electronic data entry will be employed via an 
Internet connection when possible using REDCap.  
 
Clinical assessment: The investigator will carry out a clinical examination at the 3, 
6, 12, and when available, 24-month visits to assess: 
• subject compliance with postoperative care instructions, 
• ability to return to work and normal activity, and 
• any procedure related or device related adverse events since discharge 
from the hospital  
• review of medication usage 
• progress towards fusion consolidation 
• Neurological status - All subjects’ neurological status will be assessed 
and recorded as intact or not intact, based upon the investigator’s motor, 
sensory and reflex evaluations. 
Subject self-assessment (Patient completed forms):    
• Each subject will be asked to complete a follow-up Oswestry Disability 
Index (ODI) form and a Back and Leg Pain VAS form at each follow-up 
visit. 
Radiographic assessment: Each subject will undergo AP, lateral and 
flexion/extension radiographs at the 3, 6, 12, and when available, 24-month visits 
as well as a CT scan at 6 months to assess: 
• integrity of the device and graft, with observation for events such as rod, 
hook, screw and/or spacer (if applicable) migration or subsidence, 
hardware fracture, and progress towards fusion consolidation  
Findings from any additional imaging studies deemed necessary by the 
investigator will be recorded and reported with study results. 
 
4.6 
Independent Radiographic Assessment 
 
An independent radiographic analysis will be performed to evaluate all images and 
assess subjects’ radiographic status. The independent radiographer will receive 
deidentified disks and will not have access to any personally identifiable 
information.  The following quantitative and qualitative assessments will be 
performed.  
 
Fusion Determination 

 
Page 13 of 17 
 
 
Fusion will be assessed by an independent radiographer when data collection is 
complete. X-rays at each visit and a lumbar CT at 6 months will be evaluated for 
fusion determination.  Interbody fusion will be graded by the method of Brantigan 
and Steffee as modified to describe the Fraser definition of locked pseudoarthrosis 
(BSF scale) (Santos et al., 2003). The grading system is as follows:   
• BSF-1: Radiographical pseudarthrosis 
• BSF-2: Radiogaphical locked pseudarthrosis 
• BSF-3: Radiographical fusion 
Radiographic Success: Radiographic success is defined by radiographical fusion 
(BSF-3) presenting bone bridges within at least half of the fusion area with at least 
the density originally achieved at surgery.  
Radiographic Failure: Radiographic failure is defined by radiographical 
pseudarthrosis (BSF-1 or -2) 
X-rays will be uploaded into the REDCap as a JPEG image at each subject visit. 
 
4.7  
Success Criteria 
4.7.1  Primary Measure of Effectiveness  
A subject will be considered a success if fusion is a Grade BSF-3 at 6 months. 
The primary outcome measure of effectiveness will be determined by the fusion 
rate at 6 months post-operatively in subjects implanted with either titanium cage 
as compared to the PEEK cage. 
4.7.2 Secondary Measure of Effectiveness 
Secondary measures of effectiveness will be determined by evidence and timing 
of fusion observed in X-rays post-operatively (3, 6, 12, and when available, 24 
months). 
 
4.8  
Subject Withdrawal 
 
It is recognized that the subject’s participation in this trial is entirely voluntary, and 
that she/he may refuse to participate and may withdraw from participation at any 
time without jeopardy to any future medical care.  It is also recognized that the 
investigator, at his/her discretion, may withdraw a subject from this study based 
upon his/her professional judgment. 
 
Other Conditions for Withdrawal: 

 
Page 14 of 17 
 
 
Any subject who develops a severe concurrent medical illness during the trial 
should be withdrawn.  This type of illness is defined as any illness that would hinder 
the subject’s ability to return for scheduled follow-up appointments.  Such a 
withdrawal will not be counted for the purposes of determining success or failure. 
 
5  
COMPLICATIONS 
 
In addition to the standard operating procedures for reporting complications per 
hospital/physician protocol, all clinical events, including both observed or 
volunteered problems, complaints, symptoms, physical signs or disease which 
either occur during the study, having been absent at baseline, or, if present at 
baseline, appear to worsen during the clinical outcomes collection study are to be 
recorded as complications in the subject’s medical record and on the appropriate 
case report form. 
 
Complications reported in the literature as most commonly associated with 
interbody and posterolateral lumbar fusion procedures include, but are not limited 
to, infection, nerve damage, blood clots, blood loss, and bowel and bladder 
problems, along with complications associated with anesthesia. A potential risk 
inherent to spinal fusion is failure of the vertebral bone and graft to properly fuse, 
a condition that may require additional surgery.   
 
5.1  
Definitions 
 
A complication is any written, electronic, or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, 
effectiveness, performance, or any indication of the failure of a medical product to 
meet a user or customer’s expectations. The complication may be the possible 
failure of a device or tissue product, labeling, or packaging to meet any of its 
specifications after it is released for distribution. 
 
6  
STATISTICAL ANALYSIS PLAN  
 
Statistical analyses will be performed as deemed appropriate to evaluate fusion 
outcomes across the groups. 
 
An interim analysis may be performed once, at minimum, half of the subject accrual 
is met. In the case early findings show a statistical difference between the two 
studied cages, enrollment will cease as investigators are unlikely to maintain 
clinical equipoise to continue to randomize patients. Similarly, if the interim 

 
Page 15 of 17 
 
analysis suggests it is unlikely the study will achieve statistical significance, the 
investigators may choose to close the trial early for futility. Currently enrolled 
subjects will be followed throughout the remainder of the study, up to 12 months 
post-surgery.  
 
 
7  
REFERENCES 
 
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APPENDIX 1 
 
 
 
Case Report Forms (CRFs)