Trial Outcomes & Findings for An Assessment of P-15 Bone Putty in Anterior Cervical Fusion With Instrumentation (NCT NCT00310440)

Last Updated: 2020-03-12

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

319 participants

Primary outcome timeframe

12 months

Results posted on

2020-03-12

Participant Flow

Participant milestones

Participant milestones
Measure	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). P-15 Synthetic osteoconductive bone substitute: Safety and efficacy of synthetic bone substitute used for fusion in spinal surgery	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. Autologous bone: Local autologous bone will be harvested, milled and placed into the cavity of the structural allograft ring
Overall Study STARTED	165	154
Overall Study COMPLETED	139	141
Overall Study NOT COMPLETED	26	13

Reasons for withdrawal

Reasons for withdrawal
Measure	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). P-15 Synthetic osteoconductive bone substitute: Safety and efficacy of synthetic bone substitute used for fusion in spinal surgery	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. Autologous bone: Local autologous bone will be harvested, milled and placed into the cavity of the structural allograft ring
Overall Study Lost to Follow-up	17	8
Overall Study Withdrawal by Subject	2	1
Overall Study Missed 12 Month Visit	7	4

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bone Graft Substitute n=165 Participants 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	Autologous Bone n=154 Participants 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 n=319 Participants Total of all reporting groups
Age, Continuous	47.7 years STANDARD_DEVIATION 9.7 • n=5 Participants	45.7 years STANDARD_DEVIATION 9.4 • n=7 Participants	46.8 years STANDARD_DEVIATION 9.6 • n=5 Participants
Sex: Female, Male Female	95 Participants n=5 Participants	97 Participants n=7 Participants	192 Participants n=5 Participants
Sex: Female, Male Male	70 Participants n=5 Participants	57 Participants n=7 Participants	127 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	157 Participants n=5 Participants	150 Participants n=7 Participants	307 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) White	151 Participants n=5 Participants	144 Participants n=7 Participants	295 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment Canada	29 participants n=5 Participants	26 participants n=7 Participants	55 participants n=5 Participants
Region of Enrollment United States	136 participants n=5 Participants	128 participants n=7 Participants	264 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

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

Outcome measures

Outcome measures
Measure	Bone Graft Substitute n=145 Participants 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	Autologous Bone n=141 Participants 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
Radiologic Fusion Fused	129 participants	121 participants
Radiologic Fusion No Evidence of Fusion	16 participants	20 participants

PRIMARY outcome

Timeframe: 12 months

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Bone Graft Substitute n=161 Participants 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	Autologous Bone n=152 Participants 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
Change in of the Overall Neck Disability Index (NDI) Score From Baseline.	28.75 units on a scale Interval 25.81 to 31.69	27.40 units on a scale Interval 24.35 to 30.45

PRIMARY outcome

Timeframe: 12 months

Population: The total number of observed subjects.

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.

Outcome measures

Outcome measures
Measure	Bone Graft Substitute n=143 Participants 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	Autologous Bone n=143 Participants 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
Neurologic Success Yes	134 participants	133 participants
Neurologic Success No	9 participants	10 participants

PRIMARY outcome

Timeframe: 12 months

Population: All enrolled subjects.

Any AE within 12 months of surgery.

Outcome measures

Outcome measures
Measure	Bone Graft Substitute n=165 Participants 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	Autologous Bone n=154 Participants 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
Complications Yes	138 participants	127 participants
Complications No	27 participants	27 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Bone Graft Substitute n=161 Participants 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	Autologous Bone n=152 Participants 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
Mean Change in Pain at Neck Visual Analog Scale (VAS).	4.45 cm Interval 4.0 to 4.9	4.39 cm Interval 3.96 to 4.82

SECONDARY outcome

Timeframe: Baseline and 12 months

Outcome measures

Outcome measures
Measure	Bone Graft Substitute n=161 Participants 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	Autologous Bone n=152 Participants 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
Mean Change at Pain at Arm and Shoulder Visual Analog Scale (VAS).	4.89 cm Interval 4.44 to 5.34	4.85 cm Interval 4.4 to 5.3

SECONDARY outcome

Timeframe: 12 months

Population: 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.

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%).

Outcome measures

Outcome measures
Measure	Bone Graft Substitute n=129 Participants 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	Autologous Bone n=129 Participants 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
Success Rates Measured by Aggregated Modified Odom's Criteria Excellent: Improvement GE 80% Deterioration LT 10%	80 participants	80 participants
Success Rates Measured by Aggregated Modified Odom's Criteria Good: Improvement GE 70% Deterioration LT 15%	25 participants	25 participants
Success Rates Measured by Aggregated Modified Odom's Criteria Fair: Improvement GE 50% Deterioration LT 20%	16 participants	15 participants
Success Rates Measured by Aggregated Modified Odom's Criteria Poor: Improvement LT 50% Deterioration GT 20%	8 participants	9 participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Bone Graft Substitute n=161 Participants 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	Autologous Bone n=152 Participants 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
Mean Change in the Short Form 36 v2 (SF-36v2) Physical Composite Score (PCS).	10.02 units on a scale Interval 8.39 to 11.66	9.95 units on a scale Interval 8.25 to 11.65

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Bone Graft Substitute n=161 Participants 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	Autologous Bone n=152 Participants 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
Mean Change in the Short Form 36 v2 (SF-36v2) Mental Health Composite Score (MCS).	8.33 score on a scale Interval 6.66 to 10.01	8.21 score on a scale Interval 6.48 to 9.95

SECONDARY outcome

Timeframe: 12 months

Population: 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.

Kyphosis is evaluated in degrees.

Outcome measures

Outcome measures
Measure	Bone Graft Substitute n=113 Participants 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	Autologous Bone n=116 Participants 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
Kyphosis	3.0 degrees Standard Deviation 5.0	3.8 degrees Standard Deviation 4.9

Adverse Events

Bone Graft Substitute

Serious events: 45 serious events

Other events: 136 other events

Deaths: 0 deaths

Autologous Bone

Serious events: 35 serious events

Other events: 128 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Lead Clinical Research Associate

Nor Consult, LLC

Phone: 2066076861

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Bone Graft Substitute n=165 participants at risk 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	Autologous Bone n=154 participants at risk 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
Musculoskeletal and connective tissue disorders Pseudarthrosis	2.4% 4/165 • Number of events 4 • Adverse events were collected at all visits between baseline and 24 months.	2.6% 4/154 • Number of events 4 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Back pain	1.8% 3/165 • Number of events 3 • Adverse events were collected at all visits between baseline and 24 months.	1.9% 3/154 • Number of events 3 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	1.2% 2/165 • Number of events 2 • Adverse events were collected at all visits between baseline and 24 months.	1.9% 3/154 • Number of events 3 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	1.8% 3/165 • Number of events 3 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	1.3% 2/154 • Number of events 2 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.8% 3/165 • Number of events 3 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Pain in extremity	1.8% 3/165 • Number of events 3 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Cervical spinal stenosis	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Neck pain	1.2% 2/165 • Number of events 2 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Osteoarthritis	1.2% 2/165 • Number of events 2 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Arthralgia	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Plantar fasciitis	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.61% 1/165 • Number of events 2 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Tenosynovitis stenosans	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Trigger finger	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Nervous system disorders Radiculopathy	5.5% 9/165 • Number of events 10 • Adverse events were collected at all visits between baseline and 24 months.	5.2% 8/154 • Number of events 9 • Adverse events were collected at all visits between baseline and 24 months.
Nervous system disorders Carpal tunnel syndrome	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	1.9% 3/154 • Number of events 4 • Adverse events were collected at all visits between baseline and 24 months.
Nervous system disorders Complex regional pain syndrome	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Nervous system disorders Convulsion	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Nervous system disorders Lumbar radiculopathy	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Nervous system disorders Myelopathy	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Nervous system disorders Radiculitis	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Nervous system disorders Radiculitis cervical	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Nervous system disorders Thoracic outlet syndrome	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Nervous system disorders Transient ischaemic attack	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Surgical and medical procedures Surgery	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	1.9% 3/154 • Number of events 3 • Adverse events were collected at all visits between baseline and 24 months.
Surgical and medical procedures Shoulder operation	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	1.3% 2/154 • Number of events 2 • Adverse events were collected at all visits between baseline and 24 months.
Surgical and medical procedures Limb operation	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Surgical and medical procedures Thyroidectomy	1.2% 2/165 • Number of events 2 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Surgical and medical procedures Arthroscopic surgery	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Surgical and medical procedures Elbow operation	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Surgical and medical procedures Gastrointestinal surgery	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Surgical and medical procedures Hernia repair	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Surgical and medical procedures Hip arthroplasty	0.61% 1/165 • Number of events 2 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Surgical and medical procedures Hysterectomy	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Surgical and medical procedures Knee arthroplasty	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Surgical and medical procedures Nasal septal operation	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Surgical and medical procedures Rotator cuff repair	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Surgical and medical procedures Shoulder arthroplasty	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Surgical and medical procedures Uterine operation	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Infections and infestations Infection	1.2% 2/165 • Number of events 2 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Infections and infestations Bronchitis	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Infections and infestations Diverticulitis	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Infections and infestations Meningitis viral	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Infections and infestations Tooth abscess	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Infections and infestations Urinary tract infection	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Respiratory, thoracic and mediastinal disorders Nasal polyps	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Respiratory, thoracic and mediastinal disorders Pharyngeal haematoma	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Injury, poisoning and procedural complications Overdose	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Injury, poisoning and procedural complications Radial nerve injury	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukaemia	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukaemia stage 0	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) T-cell lymphoma	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Gastrointestinal disorders Oesophageal rupture	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Gastrointestinal disorders Retroperitoneal fibrosis	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
General disorders Hernia	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
General disorders Implant site effusion	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Skin and subcutaneous tissue disorders Dermal cyst	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Skin and subcutaneous tissue disorders Ingrowing nail	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.
Cardiac disorders Pericarditis	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Investigations Blood urine present	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.
Renal and urinary disorders Nephrolithiasis	0.00% 0/165 • Adverse events were collected at all visits between baseline and 24 months.	0.65% 1/154 • Number of events 2 • Adverse events were collected at all visits between baseline and 24 months.
Reproductive system and breast disorders Breast mass	0.61% 1/165 • Number of events 1 • Adverse events were collected at all visits between baseline and 24 months.	0.00% 0/154 • Adverse events were collected at all visits between baseline and 24 months.

Measure	Bone Graft Substitute n=165 participants at risk 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	Autologous Bone n=154 participants at risk 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
Musculoskeletal and connective tissue disorders Neck pain	40.6% 67/165 • Number of events 90 • Adverse events were collected at all visits between baseline and 24 months.	47.4% 73/154 • Number of events 100 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Pain in extremity	18.8% 31/165 • Number of events 36 • Adverse events were collected at all visits between baseline and 24 months.	14.9% 23/154 • Number of events 30 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Back pain	16.4% 27/165 • Number of events 27 • Adverse events were collected at all visits between baseline and 24 months.	16.2% 25/154 • Number of events 28 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	13.9% 23/165 • Number of events 26 • Adverse events were collected at all visits between baseline and 24 months.	13.6% 21/154 • Number of events 23 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Muscle spasms	9.1% 15/165 • Number of events 15 • Adverse events were collected at all visits between baseline and 24 months.	14.3% 22/154 • Number of events 25 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Pseudarthrosis	10.3% 17/165 • Number of events 20 • Adverse events were collected at all visits between baseline and 24 months.	11.7% 18/154 • Number of events 23 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Arthralgia	6.7% 11/165 • Number of events 11 • Adverse events were collected at all visits between baseline and 24 months.	6.5% 10/154 • Number of events 10 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	7.9% 13/165 • Number of events 15 • Adverse events were collected at all visits between baseline and 24 months.	5.2% 8/154 • Number of events 9 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Myalgia	5.5% 9/165 • Number of events 10 • Adverse events were collected at all visits between baseline and 24 months.	5.2% 8/154 • Number of events 8 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	3.0% 5/165 • Number of events 5 • Adverse events were collected at all visits between baseline and 24 months.	7.1% 11/154 • Number of events 12 • Adverse events were collected at all visits between baseline and 24 months.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	3.6% 6/165 • Number of events 9 • Adverse events were collected at all visits between baseline and 24 months.	6.5% 10/154 • Number of events 12 • Adverse events were collected at all visits between baseline and 24 months.
Nervous system disorders Radiculopathy	29.1% 48/165 • Number of events 75 • Adverse events were collected at all visits between baseline and 24 months.	35.7% 55/154 • Number of events 74 • Adverse events were collected at all visits between baseline and 24 months.
Nervous system disorders Headache	10.3% 17/165 • Number of events 18 • Adverse events were collected at all visits between baseline and 24 months.	14.9% 23/154 • Number of events 29 • Adverse events were collected at all visits between baseline and 24 months.
Nervous system disorders Hypoaesthesia	8.5% 14/165 • Number of events 16 • Adverse events were collected at all visits between baseline and 24 months.	13.0% 20/154 • Number of events 27 • Adverse events were collected at all visits between baseline and 24 months.
Nervous system disorders Carpal tunnel syndrome	7.3% 12/165 • Number of events 12 • Adverse events were collected at all visits between baseline and 24 months.	5.8% 9/154 • Number of events 11 • Adverse events were collected at all visits between baseline and 24 months.
Nervous system disorders Paraesthesia	4.2% 7/165 • Number of events 8 • Adverse events were collected at all visits between baseline and 24 months.	7.8% 12/154 • Number of events 14 • Adverse events were collected at all visits between baseline and 24 months.
Gastrointestinal disorders Dysphagia	18.8% 31/165 • Number of events 32 • Adverse events were collected at all visits between baseline and 24 months.	19.5% 30/154 • Number of events 31 • Adverse events were collected at all visits between baseline and 24 months.