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

Study Overview
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Brief Summary
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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..

Detailed Description
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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.

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

Conditions
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Intervertebral Disk Degeneration

Intervention / Treatment
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* Device: P-15 Synthetic osteoconductive bone substitute
* Other: Autologous bone


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bone graft substitute<br>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<br>* Safety and efficacy of synthetic bone substitute used for fusion in spinal surgery<br>* Other names: i-Factor;|
| Active Comparator: Autologous Bone<br>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<br>* Local autologous bone will be harvested, milled and placed into the cavity of the structural allograft ring<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiologic Fusion | 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. | 12 months | 
| Change in of the Overall Neck Disability Index (NDI) Score From Baseline. | 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. | 12 months | 
| Neurologic Success | 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. | 12 months | 
| Complications | Any AE within 12 months of surgery. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Pain at Neck Visual Analog Scale (VAS). | 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. | Baseline and 12 months | 
| Mean Change at Pain at Arm and Shoulder Visual Analog Scale (VAS). | 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. | Baseline and 12 months | 
| Success Rates Measured by Aggregated Modified Odom's Criteria | 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%). | 12 months | 
| Mean Change in the Short Form 36 v2 (SF-36v2) Physical Composite Score (PCS). | 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). | Baseline and 12 months | 
| Mean Change in the Short Form 36 v2 (SF-36v2) Mental Health Composite Score (MCS). | 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). | Baseline and 12 months | 
| Kyphosis | Kyphosis is evaluated in degrees. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Degenerative disc disease, P-15 Bone Putty, Bone graft, Cervical discectomy, Cervical spine