rhBMP-2 Versus Vivigen, a Novel Cellular Allograft, in Lumbar Fusion Procedures: a Prospective Randomized Controlled Study
Phase: PHASE4
Conditions: Lumbar Spine Degeneration
Sponsor: Virtua Health, Inc.

MAR 8, 2018 
IRB Application for Population Health and Quality Research Study 
Title of Study: rhBMP-2 versus Vivigen, a novel cellular allograft, in lumbar fusion procedures: a 
prospective randomized controlled study  
 
Background and Statement of Context 
Instrumented lumbar fusion procedures with bone graft are one of the most common procedures 
performed today. There are numerous bone graft options, including iliac crest bone graft, local 
autograft, allograft, extenders, and rhBMP [1].  Several studies have demonstrated the efficacy and 
complications associated with these bone graft options [2-6]. Iliac crest autograft, long considered the 
gold standard of bone graft, is associated with donor site morbidity, longer operative times, and limited 
availability [7]. Recombinant human bone morphonogenetic protein-2 (Infuse) has revolutionized 
lumbar fusion surgery. Initially approved for a single level ALIF, Infuse has been utilized in many off-label 
applications.  Further studies of Infuse demonstrated multiple adverse effects, such as osteolysis, 
ectopic bone formation, retrograde ejaculation, and potentially carcinogenesis [8].  The premium cost 
and adverse effects of Infuse has led researchers to develop other options. A novel bone graft option is 
the cellular allograft, a cryopreserved mixture of viable bone cells, demineralized bone matrix, and 
cancellous bone chips. This product is purported to be osteogenic, osteoinductive, and osteoconductive. 
There is a paucity of literature evaluating these cellular allograft bone graft options in lumbar spine 
surgery. This study is aimed at comparing the overall efficacy (clinical and radiographic) of Vivigen, a 
novel cellular allograft product, and rhBMP-2 when utilized in lumbar fusion procedures. 
Study Questions/Objectives and Hypothesis 
The purpose of this study is to compare the overall efficacy (clinical outcome and radiographic fusion) of 
Vivigen (cellular allograft product) and rhBMP-2 in patients who undergo a single level lumbar 
instrumented fusion. Specifically, when compared to their control group counterparts treated to rhBMP-
2, we hypothesize that the intervention group administered Vivigen would, following surgery, 
experience: 
1. 
Comparable mean postoperative leg/back pain score, where the pain scores are obtained using 
the numeric rating scale of 0-no pain, to 10-worst pain possible 
2. 
Comparable inpatient length of stay (LOS) 
3. 
Comparable postoperative Oswestry Disability Index (ODI) score (0-no disability, to 100-
maximum disability possible), two weeks, 6 weeks, 3 months, 6 months, and 1 year 
postoperatively 
4.  
Comparable fusion rates, evaluated via CT scan I year postoperatively 
 Study Benefits to Virtua 

MAR 8, 2018 
Virtua could stand to gain some significant cost savings if the more cost-effective Vivigen is shown to be 
a clinically equivalent bone graft option that can replace the more expensive rhBMP-2. 
        
Study Methodology 
Patients who meet all of the following inclusion criteria may be eligible to participate in the study if: 
1. 
Age 18 or older; 
2. 
Diagnosed with lumbar degenerative/isthmic spondylolisthesis, degenerative disc disease with 
axial low back pain and neurologic symptoms, failed conservative treatment and eligible for a 
single level lumbar instrumented fusion; 
3. 
Willing to provide informed consent, participate in study, and comply with study protocol. 
Patients who meet any of the following criteria may not be eligible to participate:  
1. 
Pregnant or contemplating pregnancy prior to surgery; 
2. 
Serious spinal conditions (e.g. spinal cord compression, cauda equina syndrome, spinal infection, 
spinal tumor, spinal fracture, inflammatory or systemic spinal arthritis); 
3. 
Surgery involving more than 2 vertebral levels; 
4. 
Worker’s compensation or personal injury related to lumbar spine (treatment outcomes may be 
affected by patient’s personal interests; could also run into potential issues with 
reimbursement). 
5. 
Lactating women 
6. 
Patients who have a known or suspected allergy to Gentamicin Sulfate, Meropenem, 
Vancomycin, Dimethyl Sulfoxide (DMSO), and Human Serum Albumin 
7. 
Immune compromised patients 
During the preoperative office visit, the surgeon will inform patients that appear to meet study eligibility 
criteria, about the study, and discuss the differences between the two bone graft options, including their 
potential risks and benefits. The surgeon will make clear to the patient that consenting to be a part of 
the study means that the patient has agreed to be randomly assigned to one of the two bone graft 
groups.  
Patients who are deemed eligible to participate in the study and are willing to participate will be asked 
by a trained study physician assistant (PA) to complete the research informed consent. This document 
will be summarized verbally by the PA and potential participants will be given the opportunity to ask 
questions about the protocol or their involvement prior to providing consent. Those who agree to 

MAR 8, 2018 
participate and provide research informed consent will be enrolled in the study, and given a copy of the 
research informed consent document. The patient’s informed consent would be added to the patient’s 
chart. 
A computer generated randomization scheme will be employed and the randomization outcomes will be 
sealed in envelopes. On the day of surgery, in the operating room, the circulating nurse will pick an 
envelope from the randomized stack, unseal the envelope, and based on the outcome (even or odd), 
assign the patient to one of the two bone graft groups. While the study intervention group (even) will 
receive 5cc Vivigen and local autograft, the control group (odd) will receive small kit rhBMP-2 with local 
autograft. Anesthesiologists will use their usual pre-operative and intra-operative techniques for all 
study participants.  
The surgical team, including the surgeons, will be blinded to the treatment options until 
decompression/instrumentation have been completed. The patients and all staff, including hospital 
nursing staff, case management, and physical therapists, will be blinded as to which bone graft 
treatment the patient received. 
The primary outcome in this study will be the mean Oswestry Disability Index (ODI) score. The ODI is one 
of the most commonly utilized condition-specific measures of disability used in the management of 
spinal disorders [9]. The ODI Version 2.0 is what the Virtua Memorial Spine Center currently uses to 
examine patient disability preoperatively, as well as two weeks, 6 weeks, 3 months, 6 months, and 1 
year postoperatively. The ODI has 10 sections of six statements with the first statement corresponding 
to a score of 0 indicating no disability and the last statement corresponding to a score of 5 indicating 
maximum possible disability. The final score which is calculated as: [total score/(5 x number of questions 
answered)] x 100%, could range from 0% to 100% [9].   
Adopting a standard deviation of 10, which is one of the most commonly used standard deviations in 
ODI studies [9], and looking to detect a mean difference of 8 in ODI scores to indicate superiority of one 
bone graft option over the other, it is estimated that for a statistical power of 80% and significance level 
of 0.05, a minimum of 26 participants will be required in each study group for a total of 52 study 
participants. To minimize the possibility of dropouts or incomplete data impacting the analysis, a 
minimum of 30 participants will be enrolled in each study group, for a total of 60 study participants.  
Secondary outcome measures in this study include the mean scores from the 36-Item Short Form Survey 
Instrument (SF-36) [10]; the mean leg/back pain scores from the numeric rating scale of 0-no pain, to 
10-worst pain possible; mean LOS; incidence of ORAEs, and fusion rates examined via CT scan 1 year 
postoperatively by an independent radiologist.  
Means will be compared between the two study groups using one-tailed 2-sample t tests, proportions 
will be compared using chi-square tests, and logistic regression will be used to analyze for confounding 
effects. All statistical analyses will be conducted in Minitab 16 Statistical Software.    
 

MAR 8, 2018 
Protection of Human Subjects 
Throughout the study, the principal investigators (Virtua Memorial spine surgeons and PAs), will be the 
only ones with access to the data collection database.  Following the completion of the study, all 
personal health information collected, including name, gender, age, significant medical comorbidities, 
and postoperative complications, will be de-identified as soon as possible prior to data analysis and any 
subsequent publications or research submissions. Patient would be told participation is purely voluntary 
with no monetary reimbursement and minimal risk of being assigned to one of the two pain 
management groups. 
 
References 
1. Rihn JA, Kirkpatrick K, Albert, TJ. Graft Options in Posterolateral and Posterior Interbody Lumbar 
Fusion. Spine 2010; 35(17):1629-39. 
2. 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 
2006; 31(22):2534-9. 
3. Epstein NE. A Preliminary Study of the Efficacy of Beta Tricalcium Phosphate as a Bone Expander 
for Instrumented Posterolateral Lumbar Fusions. Journal of Spinal Disorders & Techniques 2006; 
19(6):424-9. 
4. Glassman SD, Carreon LY, Djurasovic M, Campbell MJ, Puno RM, Johnson JR, Dimar JR. RhBMP-2 
Versus Iliac Crest Bone Graft for Lumbar Spine Fusion: A Randomized, Controlled Trial in Patients 
Over Sixty Years of Age. Spine 2008; 33(26):2843-9. 
5. Dimar II JR, Glassman SD, Burkus JK, Pryor PW, Hardacker JW, Carreon LY. Two-year fusion and 
clinical outcomes in 224 patients treated with a single-level instrumented posterolateral fusion 
with iliac crest bone graft. The Spine Journal 2009; 9(11):916-8. 
6. Vaccaro AR, Patel T, Fischgrund J, Anderson DG, Truumees E, Herkowitz HN, Phillips F; Hilibrand 
A, Albert TJ; Wetzel T, McCulloch JA. A Pilot Study Evaluating the Safety and Efficacy of OP-1 
Putty (rhBMP-7) as a Replacement for Iliac Crest Autograft in Posterolateral Lumbar Arthrodesis 
for Degenerative Spondylolisthesis. Spine 2004; 29(17):1885-92. 
7. Vaccaro AR, Whang PG, Patel T, Phillips FM, Anderson DG, Albert TJ, Hilibrand AS, Brower RS, 
Kurd MF, Appannagari A, Patel M, Fischgrund JS. The safety and efficacy of OP-1 (rhBMP-7) as a 
replacement for iliac crest autograft for posterolateral lumbar arthrodesis: minimum 4-year 
follow-up of a pilot study. The Spine Journal 2008; 8(3):457-65. 
8. Carragee EJ, Ghanayem AJ, Weiner BK, Rothman DJ, Bono CM. A challenge to integrity in spine 
publications: years of living dangerously with the promotion of bone growth factors. The Spine 
Journal 2011; 11(6):463-8. 
9. Fairbank JCT, Pynsent PB. The Oswestry Disability Index. Spine 2000; 25(22):2940-53. 

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10. RAND 
Corporation. 
36-Item 
Short 
Form 
Survey 
Instrument 
(SF-36). 
http://www.rand.org/content/dam/rand/www/external/health/surveys_tools/mos/mos_core_
36item_survey.pdf 

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APPENDIX 3. The Oswestry Disability Index Questionnaire