BIO4 Clinical Case Study: Cervical Spine

Clinical and Radiographic Outcomes of BIO4 Bone Matrix in Patients Undergoing 1 or 2-Level Anterior Cervical Discectomy and Fusion Surgery

The goal of this study is to investigate the efficacy of BIO4 bone matrix in patients undergoing 1 or 2-level Anterior Cervical Discectomy and Fusion (ACDF) spine surgery. Specifically, the study aims to collect the data for ACDF model utilizing BIO4 with Bio AVS Cervical Allograft (with graft window).

Study Overview

• Status: Completed
• Conditions: Degenerative Disc Disease; Spondylolisthesis; Trauma (Including Fractures)
• Intervention / Treatment: Biological: 1 or 2-Level ACDF utilizing BIO4 with Bio AVS Cervical Allograft (with graft window).; Device: Aviator Anterior Cervical Plating System

Detailed Description

This is a prospective study with the intent to investigate the efficacy of BIO4 bone matrix in patients undergoing 1 or 2-level Anterior Cervical Discectomy and Fusion (ACDF) spine surgery. At the time a patient is scheduled for surgery, the patient's chart will be evaluated for inclusion/exclusion criteria. If a patient meets the criteria for the study, the study will be explained to the patient and consent obtained.

Investigators will utilize the BIO4 on label as a 361 HCT/P (human cell, tissue and cellular and tissue-based product) for homologous use for the repair, replacement or reconstruction of bone defects. Interbody fusion (1 or 2-level fusion) in conjunction with an allograft (hct/p) interbody spacer (anterior approach in the cervical spine with hardware) will be utilized.

Investigators will also use the Aviator Anterior Cervical Plating System for anterior intervertebral screw fixation of the cervical spine at levels C2-T1. The Aviator Anterior Cervical Plating System is intended for use as an aid in cervical spinal fusion and is intended for unilateral fixation. The Aviator plates are intended to be used with the Aviator bone screws.

Study Outcomes:

• Radiological assessment (cervical spine x-ray and if needed, computed tomography (CT) at 1 year follow up)of fusion as the primary endpoint
• Arthrodesis rates assessed using CT (1 year follow up, if needed) and Anterior-Posterior (AP), lateral and dynamic flexion-extension cervical spine x-rays pre-operative (pre-op), post-operatively (post-op) 2~4 weeks (10~34 days post op), 3 months (83~97 days post-op), 6 months (173~187 days post-op) and 1 year post-op (351~379 days post op, primary data point outcome)
• Revision rates
• Outcome scores: Visual Analog Scale (VAS) and Neck Disability Index (NDI) pre-op, post-op 2~ 4weeks, 3 months, 6 months and 1 year.

The null hypothesis is that in ACDF model, the clinical and radiographic outcomes of utilizing BIO4 bone matrix with Bio AVS Cervical Allograft are equivalent to historical high level published data of similar product (Data reported in Meta-analysis ACDF obtained from FDA disc arthroplasty trials).

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78731
      • Seton Spine and Scoliosis Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Age>18 years
2. Scheduled 1 or 2-level ACDF spine surgery
3. The capacity to provide informed consent.

4. Subject has one or more of the following diagnoses:

   1. Degenerative Disc Disease (as defined by neck pain of discogenic origin with degeneration of the disc confirmed by patient history and radiographic studies)
   2. Trauma (including fractures)
   3. Tumors
   4. Deformities or curvatures (including kyphosis, lordosis, or scoliosis)
   5. Pseudoarthrosis
   6. Failed previous fusion
   7. Decompression of the spinal cord following total or partial cervical vertebrectomy
   8. Spondylolisthesis
   9. Spinal stenosis

Exclusion Criteria Patients with any of the following conditions will be excluded, or if enrolled and found to be ineligible and do not fit the inclusion criteria, will be withdrawn from the study.

1. Patients with current or recent history of malignancy or infectious disease.
2. The inability to provide informed consent.
3. Subject has marked local inflammation
4. Subject has any mental or neuromuscular disorder which would create an unacceptable risk of fixation failure or complications in postoperative care.
5. Subject has a bone stock compromised by disease, infection or prior implantation which cannot provide adequate support and/or fixation to the devices.
6. Subject has bone abnormalities preventing safe screw fixation.
7. Subject has any open wounds.
8. Subject has rapid joint disease, bone absorption, osteopenia, osteomalacia, and/or osteoporosis. Osteoporosis or osteopenia are relative contraindications, since this condition may limit the degree of obtainable correction and/or the amount of mechanical fixation.
9. Subject has a documented or suspected metal sensitivity.
10. Subject is pregnant.
11. Subject has anatomical structures or physiological performance that would interfere with implant utilization.
12. Subject has inadequate tissue coverage over the operative site.
13. Subject has other medical or surgical conditions which would preclude the potential benefit of surgery, such as congenital abnormalities, immunosuppressive disease, elevation of sedimentation rate unexplained by other diseases, elevation of white blood count (WBC), or marked left shift in the WBC differential count.
14. Note: The Aviator Anterior Cervical Plating System is not approved or intended for screw attachment to the posterior elements (pedicles) of the cervical, thoracic, or lumbar spine. The surgeon must consider the levels of implantation, patient weight, patient activity level, and other patient conditions which may impact on the performance of the system.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: BIO4 treatment; Patients undergoing 1 or 2-level Anterior Cervical Discectomy and Fusion (ACDF) spine surgery utilizing BIO4 with Bio AVS Cervical Allograft (with graft window).

Biological: 1 or 2-Level ACDF utilizing BIO4 with Bio AVS Cervical Allograft (with graft window).; The study will utilize the BIO4 on label as a 361 HCT/P (human cell, tissue and cellular and tissue-based product) for homologous use for the repair, replacement or reconstruction of bone defects. Interbody fusion (1 or 2-level fusion) in conjunction with an allograft (hct/p) interbody spacer (anterior approach in the cervical spine with hardware). Investigators will also use the Aviator Anterior Cervical Plating System for anterior intervertebral screw fixation of the cervical spine at levels C2-T1. The Aviator Anterior Cervical Plating System is intended for use as an aid in cervical spinal fusion and is intended for unilateral fixation. The Aviator plates are intended to be used with the Aviator bone screws.; Device: Aviator Anterior Cervical Plating System; The study will utilize the BIO4 on label as a 361 HCT/P (human cell, tissue and cellular and tissue-based product) for homologous use for the repair, replacement or reconstruction of bone defects. Interbody fusion (1 or 2-level fusion) in conjunction with an allograft (hct/p) interbody spacer (anterior approach in the cervical spine with hardware). Investigators will also use the Aviator Anterior Cervical Plating System for anterior intervertebral screw fixation of the cervical spine at levels C2-T1. The Aviator Anterior Cervical Plating System is intended for use as an aid in cervical spinal fusion and is intended for unilateral fixation. The Aviator plates are intended to be used with the Aviator bone screws.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiological Assessment : Fusion Status	This will be used to monitor the fusion status at 1 year post-op. The fusion states was reported as the number of patients who fused. If fused, then we say "Yes". We counted the number of patients who fused. If all 20 patients fused then we said there were 20 "yes".	Post-op 1 year
Arthrodesis Rates	Anterior-Posterior (AP), lateral and dynamic flexion-extension cervical spine x-rays will be used to access arthrodesis rates at different time intervals. We counted the number of patients who developed arthrodesis. The arthrodesis rate was calculated as the number of patients who developed arthrodesis.	Post-op 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Revision Rates (if Any)	As needed, any post-operative surgical revision rates will be accessed. The revision rate was described as the number of patients who had to undergo revision post index surgery	Post-op 2~4 weeks
Revision Rates (if Any)	As needed, any post-operative surgical revision rates will be accessed. The revision rate was described as the number of patients who had to undergo revision post index surgery	Post-op 3 months
Revision Rates (if Any)	As needed, any post-operative surgical revision rates will be accessed. The revision rate was described as the number of patients who had to undergo revision post index surgery	Post-op 6 months
Revision Rates (if Any)	As needed, any post-operative surgical revision rates will be accessed. The revision rate was described as the number of patients who had to undergo revision post index surgery	Post-op 1 year
VAS	Patient reported VAS will be collected at different time intervals. The revision rate was described as the number of patients who had to undergo revision post index surgery. VAS: 0-10 (0=better, 10=worst)	Pre-op
VAS	Patient reported VAS will be collected at different time intervals. VAS: 0-10 (0=better, 10=worst)	Post-op 2 ~ 4 weeks
VAS	Patient reported VAS will be collected at different time intervals. VAS: 0-10 (0=better, 10=worst)	Post-op 3 months
VAS	Patient reported VAS will be collected at different time intervals. VAS: 0-10 (0=better, 10=worst)	Post-op 6 months
VAS	Patient reported VAS will be collected at different time intervals. VAS: 0-10 (0=better, 10=worst)	Post-op 1 year
NDI	Patient reported NDI will be collected at different time intervals. NDI: 0-100 (0=better, 100=worst)	Pre-op
NDI	Patient reported NDI will be collected at different time intervals NDI: 0-100 (0=better, 100=worst)	Post-op 2~4 weeks
NDI	Patient reported NDI will be collected at different time intervals. NDI: 0-100 (0=better, 100=worst)	Post-op 3 months
NDI	Patient reported NDI will be collected at different time intervals. NDI: 0-100 (0=better, 100=worst)	Post-op 6 months
NDI	Patient reported NDI will be collected at different time intervals. NSI: 0-100 (0=better, 100=worst)	Post-op 1 year
Arthrodesis Rates	Anterior-Posterior (AP), lateral and dynamic flexion-extension cervical spine x-rays will be used to access arthrodesis rates at different time intervals. The arthrodesis rate was calculated as the number of patients who developed arthrodesis.	Pre-op
Arthrodesis Rates	Anterior-Posterior (AP), lateral and dynamic flexion-extension cervical spine x-rays will be used to access arthrodesis rates at different time intervals. The arthrodesis rate was calculated as the number of patients who developed arthrodesis.	Post-op 2~4 weeks
Arthrodesis Rates	Anterior-Posterior (AP), lateral and dynamic flexion-extension cervical spine x-rays will be used to access arthrodesis rates at different time intervals. The arthrodesis rate was calculated as the number of patients who developed arthrodesis.	Post-op 3 months
Arthrodesis Rates	Anterior-Posterior (AP), lateral and dynamic flexion-extension cervical spine x-rays will be used to access arthrodesis rates at different time intervals. The arthrodesis rate was calculated as the number of patients who developed arthrodesis.	Post-op 6 months

Collaborators and Investigators

• Sponsor: Seton Healthcare Family
• Investigators: Principal Investigator: Eeric Truumees, MD, Seton Spine and Scoliosis Center

Publications and helpful links

General Publications

• Roberts TT, Rosenbaum AJ. Bone grafts, bone substitutes and orthobiologics: the bridge between basic science and clinical advancements in fracture healing. Organogenesis. 2012 Oct-Dec;8(4):114-24. doi: 10.4161/org.23306. Epub 2012 Oct 1.
• • Osiris Therapeutics-Data on File
• • Bourke HE, Sandison A, Hughes SPF and Reichert ILH. Vascular Endothelial Growth Factor (VEGF) in Human Periosteum- Normal Expression and Response to Fracture, "Journal of Bone and Joint Surgery, British Volume (2003)
• Epstein NE. An analysis of noninstrumented posterolateral lumbar fusions performed in predominantly geriatric patients using lamina autograft and beta tricalcium phosphate. Spine J. 2008 Nov-Dec;8(6):882-7. doi: 10.1016/j.spinee.2007.11.005. Epub 2008 Feb 14.
• Epstein NE. Beta tricalcium phosphate: observation of use in 100 posterolateral lumbar instrumented fusions. Spine J. 2009 Aug;9(8):630-8. doi: 10.1016/j.spinee.2009.04.007. Epub 2009 Jun 4.
• Eastlack RK, Garfin SR, Brown CR, Meyer SC. Osteocel Plus cellular allograft in anterior cervical discectomy and fusion: evaluation of clinical and radiographic outcomes from a prospective multicenter study. Spine (Phila Pa 1976). 2014 Oct 15;39(22):E1331-7. doi: 10.1097/BRS.0000000000000557.

Study record dates

Study Major Dates

• Study Start (Actual): April 6, 2017
• Primary Completion (Actual): January 30, 2020
• Study Completion (Actual): January 30, 2020

Study Registration Dates

• First Submitted: February 27, 2017
• First Submitted That Met QC Criteria: March 6, 2017
• First Posted (Actual): March 10, 2017

Study Record Updates

• Last Update Posted (Actual): January 14, 2022
• Last Update Submitted That Met QC Criteria: December 16, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Tumor; Total cervical vertebrectomy; Partial cervical vertebrectomy; Failed previous fusion; Spinal stenosis; Decompression of the spinal cord; Pseudoarthrosis; Curvatures; Deformities
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Spinal Diseases; Bone Diseases; Spondylolysis; Spondylosis; Intervertebral Disc Degeneration; Spondylolisthesis
• Other Study ID Numbers: CR-16-109

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes