Investigation of the Two Level Simplify® Cervical Artificial Disc

Study Overview
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Brief Summary
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This study is intended to demonstrate that the Simplify® Cervical Artificial Disc (Simplify® Disc) is at least as safe and effective as conventional anterior cervical discectomy and fusion (ACDF) when used to treat two contiguous discs from C3 to C7 following discectomy at two contiguous levels for intractable radiculopathy (arm pain and/or a neurological deficit) with neck pain or myelopathy due to abnormalities localized to the levels of the two contiguous disc spaces in subjects who are unresponsive to conservative management.

Detailed Description
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The objective of this clinical study is to evaluate the safety and effectiveness of the two-level Simplify® Disc compared to conventional two-level ACDF in skeletally mature patients for reconstruction of two contiguous discs from C3 to C7 following discectomy at two contiguous levels for intractable radiculopathy (arm pain and/or a neurological deficit) with neck pain or myelopathy due to abnormalities localized to the levels of the two contiguous disc spaces that are unresponsive to conservative management.

Official Title
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Clinical Study Protocol for the Investigation Of The Two Level Simplify® Cervical Artificial Disc

Conditions
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Cervical Degenerative Disc Disorder

Intervention / Treatment
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* Device: Simplify Disc


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has cervical degenerative disc disease at two (2) adjacent cervical levels (from C3 C7) requiring surgical treatment and involving intractable radiculopathy, myelopathy, or both; Has a herniated disc and/or osteophyte formation at each level to be treated that is producing symptomatic nerve root and/or spinal cord compression. The condition is documented by patient history (e.g., neck pain with arm pain, functional deficit and/or neurological deficit), and the requirement for surgical treatment is evidenced by radiographic studies (e.g., CT, MRI, x-rays, etc.); Has been unresponsive to non-operative treatment for at least six weeks or has the presence of progressive symptoms or signs of nerve root/spinal cord compression in the face of continued non-operative management; Has no previous surgical intervention at the involved levels or any subsequent planned/staged surgical procedure at the involved or adjacent level(s); Must be at least 18 years of age and be skeletally mature at the time of surgery; Has a preoperative Neck Disability Index (NDI) ≥ 30; Has a preoperative neck pain score > 8 based on the preoperative Neck and Arm Pain Questionnaire; If a female of childbearing potential, patient is non-pregnant, non-nursing, and agrees not to become pregnant during the study period; Is willing to comply with the study plan and sign the Patient Informed Consent Form. Exclusion Criteria: Has a cervical spinal condition other than symptomatic cervical DDD requiring surgical treatment at the involved levels; Has documented or diagnosed cervical instability relative to adjacent segments at either level, defined by dynamic (flexion/extension) radiographs showing: Sagittal plane translation > 3.5 mm, or Sagittal plane angulation > 20°; Has more than two cervical levels requiring surgical treatment; Has a fused level (or artificial disc replacement) adjacent to the levels to be treated; Has severe pathology of the facet joints of the involved vertebral bodies; Has had previous surgical intervention at either one or both of the involved levels or at adjacent levels; Axial neck pain only (no radicular or myelopathy symptoms); Has been previously diagnosed with osteopenia or osteomalacia; Has any of the following that may be associated with a diagnosis of osteoporosis (if Yes to any of the below risk factors, a DEXA Scan will be required to determine eligibility): Postmenopausal non-black female over 60 years of age who weighs less than 140 pounds; Postmenopausal female who has sustained a non-traumatic hip, spine, or wrist fracture; Male over the age of 70; Male over the age of 60 who has sustained a non-traumatic hip or spine fracture. If the level of bone mineral density is a T score of -1.5 or lower (i.e., -1.6, 1.7, etc.), then the patient is excluded from the study Has presence of spinal metastases; Has overt or active bacterial infection, either local or systemic; Has insulin-dependent diabetes; Has chronic or acute renal failure or prior history of renal disease; Known PEEK, ceramic, titanium allergy; Is mentally incompetent (if questionable, obtain psychiatric consult); Is a prisoner; Is pregnant; Is currently an alcohol and/or drug abuser or currently undergoing treatment for alcohol and/or drug abuse; Is involved with current or pending litigation regarding a spinal condition; Has received drugs that may interfere with bone metabolism within two weeks prior to the planned date of spinal surgery (e.g., steroids or methotrexate), excluding routine perioperative anti-inflammatory drugs; Has a history of an endocrine or metabolic disorder known to affect osteogenesis (e.g., Paget's Disease, renal osteodystrophy, Ehlers-Danlos Syndrome, or osteogenesis imperfecta); Has a condition that requires postoperative medications that interfere with the stability of the implant, such as steroids. (This does not include low-dose aspirin for prophylactic anticoagulation and routine perioperative anti-inflammatory drugs); Has received treatment with an investigational therapy within 28 days prior to implantation surgery or such treatment is planned during the 16 weeks following implantation.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simplify Disc<br>Simplify Disc at two levels of the cervical spine | Device: Simplify Disc<br>* Simplify Disc at two levels of the cervical spine<br>|
| No Intervention: Historical Control<br>This study will utilize a non-concurrent historical control with subject-level data on a parallel group design. The historical control group will be formed from the randomized ACDF arm of a previously completed two level cervical disc trial. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Clinical Success (CCS) Rate of the Simplify® Disc | Individual success is defined as at least a 15 point improvement in Neck Disability Index (NDI) Score at 24 months compared with baseline, maintenance or improvement in neurologic status at 24 months compared with baseline, no additional surgical procedure at the index level within 24 months, and the absence of a serious adverse event classified as implant-associated or implant/surgical procedure-associated within 24 months. NDI scale is reported in a range from 0 - 100, with 0 consistent with best ability to function and 100 with worst ability to function. | 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurological Status | Neurological success was defined as maintenance or improvement in neurologic status at Month 24 as compared to baseline, as determined by the independent Clinical Events Committee (CEC). The CEC reviews neurological exams of motor, sensory, reflex, and myelopathic gait to make an adjudication determination. | Baseline, 24mos | 
| Number of Subjects With 15-point Improvement in NDI at 3 Months (Time to Recovery) | Time to recovery is defined as time to first 15-point improvement in NDI NDI scale is reported in a range from 0 - 100, with 0 consistent with best ability to function and 100 with worst ability to function. | Baseline, 3mos | 
| Neck Pain Intensity Questionnaire | Changes of at least 2 points on a 10-point scale will be regarded as clinically significant (0=no pain; 10=worst pain) | Baseline, 24mos. | 
| Arm Pain Intensity Questionnaire | Changes of at least 2 points on a 10-point scale will be regarded as clinically significant (0=no pain; 10=worst pain) | Baseline, 24mos. | 
| Patient Questionnaires- Treatment Satisfaction Survey | Question 1 - I am satisfied with the results of my surgery was compared between groups at Month 24. Answer options ranged from definitely true to definitely false. | Baseline, 24mos. | 
| SF-36v2 Health Survey Physical Component Score (PCS) Maintenance or Improvement | The PCS is a sub-score of the SF-36. The SF-36 is a multipurpose survey with 36 questions. The questions were combined, scored, and weighted to create two scores that provide glimpses into mental and physical functioning and overall health-related quality-of-life. Higher scores indicate better outcomes. Scores range from 0-50. Maintenance or improvement was defined as PCS(Postop) - PCS(Preop) ≥0. | Baseline, 24mos | 
| SF-36 Mental Component Score (MCS) Maintenance or Improvement | The MCS is a sub-score of the SF-36. The SF-36 is a multipurpose survey with 36 questions. The questions were combined, scored, and weighted to create two scores that provide glimpses into mental and physical functioning and overall health-related quality-of-life. Higher scores indicate better outcomes. Scores range from 0-50. Maintenance or improvement was defined as MCS(Postop) - MCS(Preop) ≥0. | Baseline, 24mos. | 
| Dysphagia Handicap Index (DHI) | Dysphagia Handicap Index (DHI scale) for the investigational Simplify® Disc at 24 months compared to baseline. A higher score is indicative of a less desirable outcome. It is scored 0-100. Data was not collected on DHI in the historical ACDF control group. Only Simplify Disc subjects are reported. This was pre-specified in the study design. | Baseline, 24mos. | 
| Physician's Perception of Results | Results at 24 months for the investigational Simplify® Disc and at 24 months for the control ACDF will also be categorized by the physician according to their perception of the results. Available responses include excellent, good, fair, and poor. Maintenance or improvement was defined as either maintenance of the assigned preoperative grade or any shift to a more favorable grade postoperatively (e.g. poor to fair, fair to good). | Baseline, 24mos. | 
| Change in Average Disc Height (Superior Index Level) | Average disc height (superior index level) at 24 months was compared to the baseline measurement and the change was calculated. Measurements were scored by an independent core lab. Average disc height is calculated as the simple average of the anterior and posterior disc heights. Data was not collected on disc height in the historical ACDF control group. Only Simplify Disc subjects are reported. This was pre-specified in the study design. | Baseline, 24mos. | 
| Change in Average Disc Height (Inferior Index Level) | Average disc height (inferior index level) at 24 months was compared to the baseline measurement and the change was calculated. Measurements were scored by an independent core lab. Average disc height is calculated as the simple average of the anterior and posterior disc heights. Data was not collected on disc height in the historical ACDF control group. Only Simplify Disc subjects are reported. This was pre-specified in the study design. | Baseline, 24M | 
| Superior Adjacent Level Disc Degeneration (ALDD) | Outcome reports the number and percentage of subjects with adjacent level disc degeneration (ALDD) above the index level based on X-ray images. Degeneration was graded as none (no degenerative changes), doubtful (Minimal osteophytosis only), minimal (Definite osteophytosis with some sclerosis of anterior part of vertebral plates), moderate (Marked osteophytosis and sclerosis of vertebral plates with slight narrowing of disk space), severe (Large osteophytes, marked sclerosis of vertebral plates, and marked narrowing of disk space), indeterminate, or unable to assess. Data was not collected on ALDD in the historical ACDF control group. Only Simplify Disc subjects are reported. This was pre-specified in the study design. | Baseline, 24mos. | 
| Inferior Adjacent Level Disc Degeneration (ALDD) | Outcome reports the number and percentage of subjects with adjacent level disc degeneration (ALDD) below the index level based on X-ray images. Degeneration was graded as none (no degenerative changes), doubtful (Minimal osteophytosis only), minimal (Definite osteophytosis with some sclerosis of anterior part of vertebral plates), moderate (Marked osteophytosis and sclerosis of vertebral plates with slight narrowing of disk space), severe (Large osteophytes, marked sclerosis of vertebral plates, and marked narrowing of disk space), indeterminate, or unable to assess. Data was not collected on ALDD in the historical ACDF control group. Only Simplify Disc subjects are reported. This was pre-specified in the study design. | Baseline, 24mos. | 
| Facet Degeneration (Superior Index Level) | Facet degeneration was assessed using MRI for the investigational Simplify Disc at 24 months compared to baseline. Degeneration was graded as none (normal facet joint space), mild (narrowing of the facet joint space and / or small osteophytes and / or mild hypertrophy of the articular process), moderate (narrowing of the facet joint space and/or moderate osteophytes and/or moderate hypertrophy of the articular process and / or mild subarticular bone erosions), severe (Narrowing of the facet joint space and/or large osteophytes and/or severe hypertrophy of the articular process and/or severe subarticular bone erosions and/or subchondral cysts), indeterminate, or unable to assess. Facet degeneration was not assessed in the ACDF historical control group, as there is no 24 month MRI. This was pre-specified in the study design. | Baseline, 24mos. | 
| Facet Degeneration (Inferior Index Level) | Facet degeneration was assessed using MRI for the investigational Simplify Disc at 24 months compared to baseline. Degeneration was graded as none (normal facet joint space), mild (narrowing of the facet joint space and / or small osteophytes and / or mild hypertrophy of the articular process), moderate (narrowing of the facet joint space and/or moderate osteophytes and/or moderate hypertrophy of the articular process and / or mild subarticular bone erosions), severe (Narrowing of the facet joint space and/or large osteophytes and/or severe hypertrophy of the articular process and/or severe subarticular bone erosions and/or subchondral cysts), indeterminate, or unable to assess. Facet degeneration was not assessed in the ACDF historical control group, as there is no 24 month MRI. This was pre-specified in the study design. | Baseline, 24mos. |