An Assessment of P-15 Bone Putty in Anterior Cervical Fusion With Instrumentation

• Sponsor: CeraPedics, Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00310440
• Collaborator: (none)
• Enrollment: 319
• Locations: 12
• Arms: 2
• Duration (Months): 160.7
• Patients Per Site: 26.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The aim of this trial is to evaluate if P-15 bone putty (investigational device) is not inferior in effectiveness and safety to local autologous bone (control device) when applied in instrumented anterior cervical discectomy and fusion (ACDF) with use of a structural allograft ring in patients with degenerative cervical disc disease..

Condition or Disease	Intervention/Treatment	Phase
Intervertebral Disk Degeneration	Device: P-15 Synthetic osteoconductive bone substitute; Other: Autologous bone	N/A

Detailed Description

Anterior Cervical Discectomy and Fusion (ACDF) is a common surgical treatment option for symptomatic degenerative cervical disk disease in patients who fail conservative treatment. i-FACTOR bone graft is a unique anorganic bone mineral (ABM) and small peptide, P-15™. P-15 is a synthetic fifteen amino acid polypeptide that mimics the cell-binding domain of Type I human collagen and is responsible for osteogenic cell attachment via alpha2-beta1 integrins.

This is randomized, controlled, multi-center, prospective FDA IDE study conducted to assess the safety and effectiveness of i-FACTOR bone graft (Cerapedics, Inc. Westminster, CO) in patients treated with single level ACDF. Patients received i-FACTOR bone graft or local autologous bone inside a structural allograft.

Study Design

• Study Type: Interventional
• Actual Enrollment: 319 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: An Assessment of P-15 Bone Putty in Anterior Cervical Fusion With Instrumentation
• Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 23, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bone graft substitute Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with P-15 synthetic osteoconductive bone substitute (investigational device).	Device: P-15 Synthetic osteoconductive bone substitute; Safety and efficacy of synthetic bone substitute used for fusion in spinal surgery; Other Names: i-Factor
Active Comparator: Autologous Bone Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with local autologous bone.	Other: Autologous bone; Local autologous bone will be harvested, milled and placed into the cavity of the structural allograft ring

Outcome Measures

Primary Outcome Measures

1. Radiologic Fusion [12 months]

   Successful fusion was based on roentgenographic examination showing: evidence of bridging trabecular bone between the involved motion segments, translational motion <3mm, and angular motion <5 degrees. If there was a lack of evidence of fusion on 12 month plain x-ray examination, a CT-scan was performed and final determination of the fusion status was made using the CT reading. The criteria for fusion on CT scans were: trabecular bone formation patterns within the intervertebral disc space and bridging bone formation that crosses the interspace.

2. Change in of the Overall Neck Disability Index (NDI) Score From Baseline. [12 months]

   The NDI consists of ten items addressing functional activities (personal care, lifting, reading, work, driving, sleeping, recreational activities), pain intensity, concentration and headache. For each item, there are six potential responses, describing increasing degrees of disability (no disability = 0 to total disability = 5). An overall NDI score, out of 100, is calculated by adding up the scores for each item and multiplying by two. A higher NDI score indicates greater disability.

3. Neurologic Success [12 months]

   The neurological endpoint is a binary variable. Neurologic success was assessed in the motor, sensory and reflex domains specific for the cervical spine as follows: maintenance or improvement of motor function in the elbow flexors (i.e. biceps muscle), elbow extensors (i.e. triceps muscle) and wrist extensors of both arms; maintenance or improvement of sensory function of both arms; maintenance or improvement of reflexes of both arms as measured at biceps tendon, triceps tendon and brachioradialis (supinator) reflex AND absence of Babinski reflex (if not present prior to surgery). Worsening of neurological status (neurological failure) was defined as a permanent decline in the subject's neurological status based on adjudication of accumulated neurological data by an independent blinded evaluator.

4. Complications [12 months]

   Any AE within 12 months of surgery.

Secondary Outcome Measures

1. Mean Change in Pain at Neck Visual Analog Scale (VAS). [Baseline and 12 months]

   The pain VAS is a continuous scale upon which the subject indicates their pain level ranging from "No pain at all" (0) to "Worst imaginable pain" (10). The change in pain is calculated by subtracting the 12 month score from the baseline score.

2. Mean Change at Pain at Arm and Shoulder Visual Analog Scale (VAS). [Baseline and 12 months]

   The pain VAS is a continuous scale upon which the subject indicates their pain level ranging from "No pain at all" (0) to "Worst imaginable pain" (10). The change in pain is calculated by subtracting the 12 month score from the baseline score.

3. Success Rates Measured by Aggregated Modified Odom's Criteria [12 months]

   Subjects selected one of four categories: Excellent (Improvement Greater than or Equal to 80%, Deterioration Less than 10%), Good (Improvement Greater than or Equal to 70%, Deterioration Less than 15%), Fair (Improvement Greater than or Equal to 50%, Deterioration Less than 20%) or Poor (Improvement Less than 50%, Deterioration Greater than 20%).

4. Mean Change in the Short Form 36 v2 (SF-36v2) Physical Composite Score (PCS). [Baseline and 12 months]

   The SF-36 v2 (Medical Outcomes Trust, Boston, MA) is a multipurpose, patient-reported short-form health survey with 36 questions available in several languages. It yields two composite scores: one for physical health (Physical Composite Score - PCS) and one for mental health (Mental Composite Score - MCS) that are comprised of eight domains. The following domains make up the PCS: physical functioning, role-physical, bodily pain, general health. The PCS ranges from a score of 0 (lowest possible level of functioning) to a score of 100 (highest possible level of functioning).

5. Mean Change in the Short Form 36 v2 (SF-36v2) Mental Health Composite Score (MCS). [Baseline and 12 months]

   The SF-36 v2 (Medical Outcomes Trust, Boston, MA) is a multipurpose, patient-reported short-form health survey with 36 questions available in several languages. It yields two composite scores: one for physical health (Physical Composite Score - PCS) and one for mental health (Mental Composite Score - MCS) that are comprised of eight domains. The following domains make up the MCS: vitality, social functioning, role-emotional, mental health. The MCS ranges from a score of 0 (lowest possible level of functioning) to a score of 100 (highest possible level of functioning).

6. Kyphosis [12 months]

   Kyphosis is evaluated in degrees.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age between 18 and 65

• Radiographically determined discogenic origin to include at least one of the following characteristics: degenerated/dark disc on MRI, decreased disc height compared to adjacent levels on radiographic film, CT, or MRI and disc herniation on CT or MRI

• Radicular symptoms by history and physical exam to include at least the following characteristics: Arm/shoulder pain, decreased flexes, decreased strength and abnormal sensation

• Pain level arm/shoulder >4 on 0-10 VAS

• Pain level neck >4 on 0-10 VAS

• Neck disability Index >30

• Involved discs between C3 and C7

• Undergoing anterior cervical fusion at a single level

• Failed to gain adequate relief from non-operative treatment

• Able and willing to give consent to participate in study

• Understand and read English at elementary level

Exclusion Criteria:

Systemic infection such as AIDS, HIV, and active hepatitis; Significant metabolic disease that in the surgeon's opinion might compromise bone growth such as osteoporosis or osteomalacia; Taking medication for the prevention of osteoporosis; Circulatory, cardiac, or pulmonary problems that could cause excessive surgical risk; Active malignancy; Nondiscogenic source of symptoms (e.g., tumor, etc.); Multiple level symptomatic degenerative disc disease; Previous cervical fusion; Previous cervical decompression at the same level; Acute cervical trauma or instability (i.e., subluxation > 3 mm on flexion/extension radiographic film); Undergoing treatment for tumor or bony traumatic injury to the cervical spine; Rheumatoid disease of the cervical spine; Myelopathy; Pregnant or planning to become pregnant in the next 2 years; Posterior cervical spine procedure scheduled; More than one level to be operated; Has a history of substance abuse (recreational drugs, alcohol); Is a prisoner; Is currently involved in a study of another investigational product for similar purpose; Has a disease process that would preclude accurate evaluation (e.g., neuromuscular disease, significant psychiatric disease).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Neurological Surgery UCSF Spine Center	San Francisco	California	United States	94143
2	Spine Education Research Institute	Thornton	Colorado	United States	80229
3	Sarasota Memorial Hospital	Sarasota	Florida	United States	34233
4	Orthopaedics Northeast/Midwest Spine Group	Fort Wayne	Indiana	United States	46825
5	Indiana Spine Group	Indianapolis	Indiana	United States	46260
6	Indianapolis Neurosurgical Group	Indianapolis	Indiana	United States	46260
7	Kansas University Medical Center	Kansas City	Kansas	United States	66160-0001
8	New England Neurosurgical Associates, LLC	Springfield	Massachusetts	United States	01104
9	Cleveland Clinic	Cleveland	Ohio	United States	44195
10	University of Utah Orthopaedic Center	Salt Lake City	Utah	United States	84108
11	Foothills Medical Center	Calgary	Alberta	Canada	T2N 2T9
12	Montreal Neurological Institute	Montreal	Quebec	Canada	H3A 2B4

Sponsors and Collaborators

• CeraPedics, Inc

Investigators

• Principal Investigator: Michael Janssen, MD / DO, Spine Education Research Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: CeraPedics, Inc
• ClinicalTrials.gov Identifier: NCT00310440
• Other Study ID Numbers: 1003
• First Posted: Apr 4, 2006
• Last Update Posted: Mar 12, 2020
• Last Verified: Mar 1, 2020

• Keywords provided by CeraPedics, Inc: Degenerative disc disease; P-15 Bone Putty; Bone graft; Cervical discectomy; Cervical spine
• Additional relevant MeSH terms: Intervertebral Disc Degeneration

Study Results

Participant Flow

Arm/Group Title	Bone Graft Substitute	Autologous Bone
Arm/Group Description	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with P-15 synthetic osteoconductive bone substitute (investigational device). P-15 Synthetic osteoconductive bone substitute: Safety and efficacy of synthetic bone substitute used for fusion in spinal surgery	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with local autologous bone. Autologous bone: Local autologous bone will be harvested, milled and placed into the cavity of the structural allograft ring
Period Title: Overall Study
STARTED	165	154
COMPLETED	139	141
NOT COMPLETED	26	13

Baseline Characteristics

Arm/Group Title	Bone Graft Substitute	Autologous Bone	Total
Arm/Group Description	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with P-15 synthetic osteoconductive bone substitute (investigational device). P-15 Synthetic osteoconductive bone substitute: Safety and efficacy of synthetic bone substitute used for fusion in spinal surgery	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with local autologous bone. Autologous bone: Local autologous bone will be harvested, milled and placed into the cavity of the structural allograft ring	Total of all reporting groups
Overall Participants	165	154	319
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.7 (9.7)	45.7 (9.4)	46.8 (9.6)
Sex: Female, Male (Count of Participants)
Female	95 57.6%	97 63%	192 60.2%
Male	70 42.4%	57 37%	127 39.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 4.2%	4 2.6%	11 3.4%
Not Hispanic or Latino	157 95.2%	150 97.4%	307 96.2%
Unknown or Not Reported	1 0.6%	0 0%	1 0.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.6%	0 0%	1 0.3%
Asian	4 2.4%	1 0.6%	5 1.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	5 3%	6 3.9%	11 3.4%
White	151 91.5%	144 93.5%	295 92.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	4 2.4%	3 1.9%	7 2.2%
Region of Enrollment (participants) [Number]
Canada	29 17.6%	26 16.9%	55 17.2%
United States	136 82.4%	128 83.1%	264 82.8%

Outcome Measures

1. Primary Outcome

Title	Radiologic Fusion
Description	Successful fusion was based on roentgenographic examination showing: evidence of bridging trabecular bone between the involved motion segments, translational motion <3mm, and angular motion <5 degrees. If there was a lack of evidence of fusion on 12 month plain x-ray examination, a CT-scan was performed and final determination of the fusion status was made using the CT reading. The criteria for fusion on CT scans were: trabecular bone formation patterns within the intervertebral disc space and bridging bone formation that crosses the interspace.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

All participants that have radiological data at 12 months including imputed data.

Arm/Group Title	Bone Graft Substitute	Autologous Bone
Arm/Group Description	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with P-15 synthetic osteoconductive bone substitute (investigational device). P-15 Synthetic osteoconductive bone substitute: Safety and efficacy of synthetic bone substitute used for fusion in spinal surgery	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with local autologous bone. Autologous bone: Local autologous bone will be harvested, milled and placed into the cavity of the structural allograft ring
Measure Participants	145	141
Fused	129 78.2%	121 78.6%
No Evidence of Fusion	16 9.7%	20 13%

2. Primary Outcome

Title	Change in of the Overall Neck Disability Index (NDI) Score From Baseline.
Description	The NDI consists of ten items addressing functional activities (personal care, lifting, reading, work, driving, sleeping, recreational activities), pain intensity, concentration and headache. For each item, there are six potential responses, describing increasing degrees of disability (no disability = 0 to total disability = 5). An overall NDI score, out of 100, is calculated by adding up the scores for each item and multiplying by two. A higher NDI score indicates greater disability.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Per protocol (PP) subjects were included in this analysis. Six subjects that had major protocol deviations with the potential to impact the primary endpoint results were not included in the PP population.

Arm/Group Title	Bone Graft Substitute	Autologous Bone
Arm/Group Description	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with P-15 synthetic osteoconductive bone substitute (investigational device). P-15 Synthetic osteoconductive bone substitute: Safety and efficacy of synthetic bone substitute used for fusion in spinal surgery	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with local autologous bone. Autologous bone: Local autologous bone will be harvested, milled and placed into the cavity of the structural allograft ring
Measure Participants	161	152
Least Squares Mean (95% Confidence Interval) [units on a scale]	28.75	27.40

3. Primary Outcome

Title	Neurologic Success
Description	The neurological endpoint is a binary variable. Neurologic success was assessed in the motor, sensory and reflex domains specific for the cervical spine as follows: maintenance or improvement of motor function in the elbow flexors (i.e. biceps muscle), elbow extensors (i.e. triceps muscle) and wrist extensors of both arms; maintenance or improvement of sensory function of both arms; maintenance or improvement of reflexes of both arms as measured at biceps tendon, triceps tendon and brachioradialis (supinator) reflex AND absence of Babinski reflex (if not present prior to surgery). Worsening of neurological status (neurological failure) was defined as a permanent decline in the subject's neurological status based on adjudication of accumulated neurological data by an independent blinded evaluator.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

The total number of observed subjects.

Arm/Group Title	Bone Graft Substitute	Autologous Bone
Arm/Group Description	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with P-15 synthetic osteoconductive bone substitute (investigational device). P-15 Synthetic osteoconductive bone substitute: Safety and efficacy of synthetic bone substitute used for fusion in spinal surgery	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with local autologous bone. Autologous bone: Local autologous bone will be harvested, milled and placed into the cavity of the structural allograft ring
Measure Participants	143	143
Yes	134 81.2%	133 86.4%
No	9 5.5%	10 6.5%

4. Primary Outcome

Title	Complications
Description	Any AE within 12 months of surgery.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

All enrolled subjects.

Arm/Group Title	Bone Graft Substitute	Autologous Bone
Arm/Group Description	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with P-15 synthetic osteoconductive bone substitute (investigational device). P-15 Synthetic osteoconductive bone substitute: Safety and efficacy of synthetic bone substitute used for fusion in spinal surgery	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with local autologous bone. Autologous bone: Local autologous bone will be harvested, milled and placed into the cavity of the structural allograft ring
Measure Participants	165	154
Yes	138 83.6%	127 82.5%
No	27 16.4%	27 17.5%

5. Secondary Outcome

Title	Mean Change in Pain at Neck Visual Analog Scale (VAS).
Description	The pain VAS is a continuous scale upon which the subject indicates their pain level ranging from "No pain at all" (0) to "Worst imaginable pain" (10). The change in pain is calculated by subtracting the 12 month score from the baseline score.
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Per protocol (PP) subjects were included in this analysis. Six subjects that had major protocol deviations with the potential to impact the primary endpoint results were not included in the PP population.

Arm/Group Title	Bone Graft Substitute	Autologous Bone
Arm/Group Description	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with P-15 synthetic osteoconductive bone substitute (investigational device). P-15 Synthetic osteoconductive bone substitute: Safety and efficacy of synthetic bone substitute used for fusion in spinal surgery	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with local autologous bone. Autologous bone: Local autologous bone will be harvested, milled and placed into the cavity of the structural allograft ring
Measure Participants	161	152
Mean (95% Confidence Interval) [cm]	4.45	4.39

6. Secondary Outcome

Title	Mean Change at Pain at Arm and Shoulder Visual Analog Scale (VAS).
Description	The pain VAS is a continuous scale upon which the subject indicates their pain level ranging from "No pain at all" (0) to "Worst imaginable pain" (10). The change in pain is calculated by subtracting the 12 month score from the baseline score.
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Per protocol (PP) subjects were included in this analysis. Six subjects that had major protocol deviations with the potential to impact the primary endpoint results were not included in the PP population.

Arm/Group Title	Bone Graft Substitute	Autologous Bone
Arm/Group Description	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with P-15 synthetic osteoconductive bone substitute (investigational device). P-15 Synthetic osteoconductive bone substitute: Safety and efficacy of synthetic bone substitute used for fusion in spinal surgery	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with local autologous bone. Autologous bone: Local autologous bone will be harvested, milled and placed into the cavity of the structural allograft ring
Measure Participants	161	152
Mean (95% Confidence Interval) [cm]	4.89	4.85

7. Secondary Outcome

Title	Success Rates Measured by Aggregated Modified Odom's Criteria
Description	Subjects selected one of four categories: Excellent (Improvement Greater than or Equal to 80%, Deterioration Less than 10%), Good (Improvement Greater than or Equal to 70%, Deterioration Less than 15%), Fair (Improvement Greater than or Equal to 50%, Deterioration Less than 20%) or Poor (Improvement Less than 50%, Deterioration Greater than 20%).
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Per protocol (PP) subjects that had data available at the 12 month visit were included in this analysis. Six subjects that had major protocol deviations with the potential to impact the primary endpoint results were not included in the PP population.

Arm/Group Title	Bone Graft Substitute	Autologous Bone
Arm/Group Description	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with P-15 synthetic osteoconductive bone substitute (investigational device). P-15 Synthetic osteoconductive bone substitute: Safety and efficacy of synthetic bone substitute used for fusion in spinal surgery	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with local autologous bone. Autologous bone: Local autologous bone will be harvested, milled and placed into the cavity of the structural allograft ring
Measure Participants	129	129
Excellent: Improvement GE 80% Deterioration LT 10%	80 48.5%	80 51.9%
Good: Improvement GE 70% Deterioration LT 15%	25 15.2%	25 16.2%
Fair: Improvement GE 50% Deterioration LT 20%	16 9.7%	15 9.7%
Poor: Improvement LT 50% Deterioration GT 20%	8 4.8%	9 5.8%

8. Secondary Outcome

Title	Mean Change in the Short Form 36 v2 (SF-36v2) Physical Composite Score (PCS).
Description	The SF-36 v2 (Medical Outcomes Trust, Boston, MA) is a multipurpose, patient-reported short-form health survey with 36 questions available in several languages. It yields two composite scores: one for physical health (Physical Composite Score - PCS) and one for mental health (Mental Composite Score - MCS) that are comprised of eight domains. The following domains make up the PCS: physical functioning, role-physical, bodily pain, general health. The PCS ranges from a score of 0 (lowest possible level of functioning) to a score of 100 (highest possible level of functioning).
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Per protocol (PP) subjects were included in this analysis. Six subjects that had major protocol deviations with the potential to impact the primary endpoint results were not included in the PP population.

Arm/Group Title	Bone Graft Substitute	Autologous Bone
Arm/Group Description	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with P-15 synthetic osteoconductive bone substitute (investigational device). P-15 Synthetic osteoconductive bone substitute: Safety and efficacy of synthetic bone substitute used for fusion in spinal surgery	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with local autologous bone. Autologous bone: Local autologous bone will be harvested, milled and placed into the cavity of the structural allograft ring
Measure Participants	161	152
Least Squares Mean (95% Confidence Interval) [units on a scale]	10.02	9.95

9. Secondary Outcome

Title	Mean Change in the Short Form 36 v2 (SF-36v2) Mental Health Composite Score (MCS).
Description	The SF-36 v2 (Medical Outcomes Trust, Boston, MA) is a multipurpose, patient-reported short-form health survey with 36 questions available in several languages. It yields two composite scores: one for physical health (Physical Composite Score - PCS) and one for mental health (Mental Composite Score - MCS) that are comprised of eight domains. The following domains make up the MCS: vitality, social functioning, role-emotional, mental health. The MCS ranges from a score of 0 (lowest possible level of functioning) to a score of 100 (highest possible level of functioning).
Time Frame	Baseline and 12 months

Outcome Measure Data

Analysis Population Description

Per protocol (PP) subjects were included in this analysis. Six subjects that had major protocol deviations with the potential to impact the primary endpoint results were not included in the PP population.

Arm/Group Title	Bone Graft Substitute	Autologous Bone
Arm/Group Description	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with P-15 synthetic osteoconductive bone substitute (investigational device). P-15 Synthetic osteoconductive bone substitute: Safety and efficacy of synthetic bone substitute used for fusion in spinal surgery	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with local autologous bone. Autologous bone: Local autologous bone will be harvested, milled and placed into the cavity of the structural allograft ring
Measure Participants	161	152
Least Squares Mean (95% Confidence Interval) [score on a scale]	8.33	8.21

10. Secondary Outcome

Title	Kyphosis
Description	Kyphosis is evaluated in degrees.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Per protocol (PP) subjects who had images available at 12 months were included in this analysis. Six subjects that had major protocol deviations with the potential to impact the primary endpoint results were not included in the PP population.

Arm/Group Title	Bone Graft Substitute	Autologous Bone
Arm/Group Description	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with P-15 synthetic osteoconductive bone substitute (investigational device). P-15 Synthetic osteoconductive bone substitute: Safety and efficacy of synthetic bone substitute used for fusion in spinal surgery	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with local autologous bone. Autologous bone: Local autologous bone will be harvested, milled and placed into the cavity of the structural allograft ring
Measure Participants	113	116
Mean (Standard Deviation) [degrees]	3.0 (5.0)	3.8 (4.9)

Adverse Events

Time Frame	Adverse events were collected at all visits between baseline and 24 months.
Arm/Group Title	Bone Graft Substitute		Autologous Bone
Arm/Group Description	Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with P-15 synthetic osteoconductive bone substitute (investigational device). P-15 Synthetic osteoconductive bone substitute: Safety and efficacy of synthetic bone substitute used for fusion in spinal surgery		Subjects will receive anterior cervical discectomy with fusion and instrumentation (anterior plate). Structural allograft ring will be used. The cavity of the ring will be filled with local autologous bone. Autologous bone: Local autologous bone will be harvested, milled and placed into the cavity of the structural allograft ring
All Cause Mortality
	Bone Graft Substitute		Autologous Bone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Bone Graft Substitute		Autologous Bone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/165 (27.3%)		35/154 (22.7%)
Cardiac disorders
Pericarditis	1/165 (0.6%)	1	0/154 (0%)	0
Gastrointestinal disorders
Oesophageal rupture	1/165 (0.6%)	1	0/154 (0%)	0
Retroperitoneal fibrosis	0/165 (0%)	0	1/154 (0.6%)	1
General disorders
Hernia	0/165 (0%)	0	1/154 (0.6%)	1
Implant site effusion	0/165 (0%)	0	1/154 (0.6%)	1
Infections and infestations
Infection	2/165 (1.2%)	2	0/154 (0%)	0
Bronchitis	0/165 (0%)	0	1/154 (0.6%)	1
Diverticulitis	1/165 (0.6%)	1	0/154 (0%)	0
Meningitis viral	1/165 (0.6%)	1	0/154 (0%)	0
Tooth abscess	0/165 (0%)	0	1/154 (0.6%)	1
Urinary tract infection	0/165 (0%)	0	1/154 (0.6%)	1
Injury, poisoning and procedural complications
Humerus fracture	0/165 (0%)	0	1/154 (0.6%)	1
Overdose	1/165 (0.6%)	1	0/154 (0%)	0
Radial nerve injury	1/165 (0.6%)	1	0/154 (0%)	0
Investigations
Blood urine present	1/165 (0.6%)	1	0/154 (0%)	0
Musculoskeletal and connective tissue disorders
Pseudarthrosis	4/165 (2.4%)	4	4/154 (2.6%)	4
Back pain	3/165 (1.8%)	3	3/154 (1.9%)	3
Intervertebral disc protrusion	2/165 (1.2%)	2	3/154 (1.9%)	3
Rotator cuff syndrome	3/165 (1.8%)	3	1/154 (0.6%)	1
Lumbar spinal stenosis	1/165 (0.6%)	1	2/154 (1.3%)	2
Musculoskeletal pain	3/165 (1.8%)	3	0/154 (0%)	0
Pain in extremity	3/165 (1.8%)	3	0/154 (0%)	0
Cervical spinal stenosis	1/165 (0.6%)	1	1/154 (0.6%)	1
Intervertebral disc degeneration	1/165 (0.6%)	1	1/154 (0.6%)	1
Neck pain	2/165 (1.2%)	2	0/154 (0%)	0
Osteoarthritis	2/165 (1.2%)	2	0/154 (0%)	0
Arthralgia	1/165 (0.6%)	1	0/154 (0%)	0
Plantar fasciitis	0/165 (0%)	0	1/154 (0.6%)	1
Rheumatoid arthritis	1/165 (0.6%)	2	0/154 (0%)	0
Spinal osteoarthritis	1/165 (0.6%)	1	0/154 (0%)	0
Tenosynovitis stenosans	1/165 (0.6%)	1	0/154 (0%)	0
Trigger finger	0/165 (0%)	0	1/154 (0.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic lymphocytic leukaemia	0/165 (0%)	0	1/154 (0.6%)	1
Chronic lymphocytic leukaemia stage 0	0/165 (0%)	0	1/154 (0.6%)	1
Renal cancer	1/165 (0.6%)	1	0/154 (0%)	0
T-cell lymphoma	1/165 (0.6%)	1	0/154 (0%)	0
Nervous system disorders
Radiculopathy	9/165 (5.5%)	10	8/154 (5.2%)	9
Carpal tunnel syndrome	0/165 (0%)	0	3/154 (1.9%)	4
Complex regional pain syndrome	1/165 (0.6%)	1	0/154 (0%)	0
Convulsion	0/165 (0%)	0	1/154 (0.6%)	1
Lumbar radiculopathy	0/165 (0%)	0	1/154 (0.6%)	1
Myelopathy	1/165 (0.6%)	1	0/154 (0%)	0
Radiculitis	0/165 (0%)	0	1/154 (0.6%)	1
Radiculitis cervical	1/165 (0.6%)	1	0/154 (0%)	0
Thoracic outlet syndrome	0/165 (0%)	0	1/154 (0.6%)	1
Transient ischaemic attack	0/165 (0%)	0	1/154 (0.6%)	1
Renal and urinary disorders
Nephrolithiasis	0/165 (0%)	0	1/154 (0.6%)	2
Reproductive system and breast disorders
Breast mass	1/165 (0.6%)	1	0/154 (0%)	0
Respiratory, thoracic and mediastinal disorders
Nasal polyps	1/165 (0.6%)	1	0/154 (0%)	0
Pharyngeal haematoma	0/165 (0%)	0	1/154 (0.6%)	1
Pulmonary mass	1/165 (0.6%)	1	0/154 (0%)	0
Sleep apnoea syndrome	0/165 (0%)	0	1/154 (0.6%)	1
Skin and subcutaneous tissue disorders
Dermal cyst	1/165 (0.6%)	1	0/154 (0%)	0
Ingrowing nail	0/165 (0%)	0	1/154 (0.6%)	1
Surgical and medical procedures
Surgery	1/165 (0.6%)	1	3/154 (1.9%)	3
Shoulder operation	1/165 (0.6%)	1	2/154 (1.3%)	2
Limb operation	1/165 (0.6%)	1	1/154 (0.6%)	1
Thyroidectomy	2/165 (1.2%)	2	0/154 (0%)	0
Arthroscopic surgery	0/165 (0%)	0	1/154 (0.6%)	1
Elbow operation	0/165 (0%)	0	1/154 (0.6%)	1
Gastrointestinal surgery	1/165 (0.6%)	1	0/154 (0%)	0
Hernia repair	0/165 (0%)	0	1/154 (0.6%)	1
Hip arthroplasty	1/165 (0.6%)	2	0/154 (0%)	0
Hysterectomy	1/165 (0.6%)	1	0/154 (0%)	0
Knee arthroplasty	0/165 (0%)	0	1/154 (0.6%)	1
Nasal septal operation	1/165 (0.6%)	1	0/154 (0%)	0
Rotator cuff repair	1/165 (0.6%)	1	0/154 (0%)	0
Shoulder arthroplasty	0/165 (0%)	0	1/154 (0.6%)	1
Uterine operation	1/165 (0.6%)	1	0/154 (0%)	0
Other (Not Including Serious) Adverse Events
	Bone Graft Substitute		Autologous Bone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	136/165 (82.4%)		128/154 (83.1%)
Gastrointestinal disorders
Dysphagia	31/165 (18.8%)	32	30/154 (19.5%)	31
Musculoskeletal and connective tissue disorders
Neck pain	67/165 (40.6%)	90	73/154 (47.4%)	100
Pain in extremity	31/165 (18.8%)	36	23/154 (14.9%)	30
Back pain	27/165 (16.4%)	27	25/154 (16.2%)	28
Musculoskeletal pain	23/165 (13.9%)	26	21/154 (13.6%)	23
Muscle spasms	15/165 (9.1%)	15	22/154 (14.3%)	25
Pseudarthrosis	17/165 (10.3%)	20	18/154 (11.7%)	23
Arthralgia	11/165 (6.7%)	11	10/154 (6.5%)	10
Musculoskeletal stiffness	13/165 (7.9%)	15	8/154 (5.2%)	9
Myalgia	9/165 (5.5%)	10	8/154 (5.2%)	8
Intervertebral disc protrusion	5/165 (3%)	5	11/154 (7.1%)	12
Musculoskeletal discomfort	6/165 (3.6%)	9	10/154 (6.5%)	12
Nervous system disorders
Radiculopathy	48/165 (29.1%)	75	55/154 (35.7%)	74
Headache	17/165 (10.3%)	18	23/154 (14.9%)	29
Hypoaesthesia	14/165 (8.5%)	16	20/154 (13%)	27
Carpal tunnel syndrome	12/165 (7.3%)	12	9/154 (5.8%)	11
Paraesthesia	7/165 (4.2%)	8	12/154 (7.8%)	14

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.