Background
Methods/Design
Inclusion Criteria
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Age 18 - 60 years and skeletally mature
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Symptomatic degenerative disc disease with objective evidence of lumbar DDD, based on identification of any of the following characteristics by MRI scan:◦ instability as defined by ≥ 3 mm translation or ≥ 5° angulation.◦ osteophyte formation of facet joints or vertebral endplates.◦ decreased disc height of > 2 mm as compared to the adjacent level.◦ scarring/thickening of the ligamentum flavum, annulus fibrosis, or facet joint capsule.◦ herniated nucleus pulposus.◦ facet joint degeneration/changes.◦ vacuum phenomenon.
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Single level symptomatic disease at L4/L5 or L5/S1.
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Minimum of six months of unsuccessful conservative treatment, including but not limited to physical therapy and/or medication.
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Minimum Oswestry Disability Index score of 40/100.
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Subject is a surgical candidate for an anterior approach to the lumbar spine.
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Back pain at the operative level only, with or without leg pain.
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Back pain, as measured using a visual analog scale (VAS), greater than the higher of the two VAS leg pain scores.
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Minimum VAS back pain score of 40/100 mm.
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Subject willing and able to return for follow-up visits regularly and sign an Informed Consent and HIPAA Authorization.
Exclusion Criteria
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Previous surgery at any lumbar level, except IDET (Intradiscal Electrothermal Annuloplasty), percutaneous nucleoplasty, microdiscectomy, hemilaminectomy, or laminotomy
-
Chronic radiculopathy as defined by subject complaint of unremitting pain with a predominance of leg pain symptoms greater than back pain symptoms extending over a period of at least 1 year.
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Anatomic requirements incompatible with the available range of dimensions for the experimental or control devices, based on preoperative assessment using radiographic templates. Specifically, endplate dimensions smaller than 34.5 mm in medial-lateral and/or 27 mm in the anterior-posterior direction
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Subjects with evidence of significant, symptomatic disc degeneration at another lumbar level.
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Preoperative remaining disc height < 3 mm
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Myelopathy.
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Previous compression or burst fracture at the affected level.
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Sequestered herniated nucleus pulposus with migration.
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Mid-sagittal stenosis of < 8 mm (by MRI).
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Degenerative or lytic spondylolisthesis > 3 mm.
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Spondylolysis.
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Isthmic spondylolisthesis.
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Lumbar scoliosis (> 11° sagittal plane deformity).
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Spinal tumor.
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Active systemic infection or infection at the site of surgery.
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Facet ankylosis or severe facet degeneration.
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Continuing steroid use or prior use for more than 2 months.
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History of allergies to any of the device components including cobalt chromium alloy, titanium, ultra high molecular weight polyethylene, and calcium phosphate.
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Pregnancy or planning to become pregnant within the next 2 years.
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Morbid obesity (BMI > 35).
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Investigational drug or device use within 30 days.
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Osteoporosis or osteopenia, indicated by a lumbar spine DXA T-score less than or equal to -1.
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Metabolic bone disease.
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Leg pain with migrated sequestrum fragment.
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History of rheumatoid arthritis, lupus, or other autoimmune disorder.
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Ankylosing spondylitis.
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History of HIV/AIDS or hepatitis that precludes surgery.
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History of deep vein thrombosis, symptoms of arterial insufficiency, or thromboembolytic disease.
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Current or recent history of illicit drug or alcohol abuse, or dependence as defined as the continued use of alcohol despite the development of social, legal, or health problems.
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Life expectancy less than 5 years.
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Undergone chemotherapy within the past 5 years, or had any cancer other than non-melanoma skin cancer treated with curative intent within the past 5 years.
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Prior nephrectomy.
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Abdominal adhesions, endometriosis, inflammatory bowel disease, Crohn's disease, diverticulitis, ulcerative colitis or other abdominal pathology that would preclude the abdominal surgical approach.
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Insulin-dependent diabetes.
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Any degenerative muscular or neurological condition that would interfere with evaluation of outcomes, including but not limited to Parkinson's disease, ALS (amyotrophic lateral sclerosis), or multiple sclerosis.
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History of Pelvic Inflammatory Disease.
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Peritonitis.
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Subjects currently in active spinal litigation as a result of medical negligence.
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Subject is a prisoner.
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Psychiatric or cognitive impairment that, in the opinion of the investigator, would interfere with the subject's ability to comply with the study requirements, e.g., Alzheimer's disease.
Treatment Procedures and Evaluations
Activ-L Disc
Control Discs (ProDisc®-L Total Disc Replacement or Charité® Artificial Disc)
Base-line | Intra-OP | Discharge | Follow-up Period from Surgery Date (± Days) | ||||||
---|---|---|---|---|---|---|---|---|---|
6 wks
(± 14)
|
3 mon
(± 14)
|
6 mon
(± 30)
|
12 mon
(± 60)
|
24 mon
(± 60)
|
3-5 yrs
(± 60)
| ||||
Inclusion/Exclusion Determination |
X
| ||||||||
Osteoporosis/ osteopenia screen |
X
| ||||||||
Medical History/Physical Exam |
X
| ||||||||
Work Status |
X
|
X
|
X
|
X
|
X
|
X
|
X
| ||
Pain Medications |
X
|
X
|
X
|
X
| |||||
Antibiotics |
X
|
X**
|
X
| ||||||
Visual Analog Scale (VAS) Pain Assessment |
X
|
X
|
X
|
X
|
X
|
X
|
X
| ||
Neurological Assessment |
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
| |
DVT Prophylaxis |
X
| ||||||||
QOL SF-36 |
X
|
X
|
X
|
X
|
X
|
X
|
X
| ||
Oswestry Disability Index (ODI) |
X
|
X
|
X
|
X
|
X
|
X
|
X
| ||
Hospital Stay |
X
| ||||||||
Range of Motion |
X
|
X
|
X
|
X
|
X
| ||||
Subject Satisfaction |
X
|
X
|
X
| ||||||
Adverse Events |
X
|
X
|
X
|
X
|
X
|
X
|
X
|
X
| |
RADIOGRAPHIC EVENTS
| |||||||||
MRI scan |
X
| ||||||||
DXA Scan |
X (IR)
| ||||||||
X-rays, A/P -- Standing Neutral |
X
|
X
(Implant Position)
|
X
(Implant Position)
|
X
|
X
|
X
|
X
|
X
|
X
|
X-rays, A/P- Right/Left Bending |
X
|
X
|
X
|
X
|
X
|
X
|
X
| ||
X-rays, Lateral - Flexion-Extension |
X
|
X
|
X
|
X
|
X
|
X
|
X
| ||
X-Rays, Lateral Standing Neutral |
X
|
X
(Implant Position)
|
X
(Implant Position)
|
X
|
X
|
X
|
X
|
X
|
X
|
Surgical Technique
Intraoperative Data Collection
-
Procedure date, time
-
Prophylactic antibiotics
-
Implanted device model number and lot number
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Surgery information including duration, approach, and use of an access surgeon
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Vertebral level treated
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AP and lateral X-rays to verify device placement
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Estimated blood loss
-
Blood transfusion information (as needed)
-
Adverse Events
-
Any implant sizing difficulties
Primary Endpoints
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Improvement of at least 15 points in the Oswestry Disability Index score at 24 months compared to baseline.
-
Maintenance or improvement in neurological status at 24 months compared to baseline as measured by motor and sensory evaluations. A decrease of one grade in either evaluation will be considered a failure.
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Maintenance or improvement in motion at the index level, defined as:
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No device failures requiring revision, re-operation, removal, or supplemental fixation.
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Absence of serious device-related adverse events (AEs). For purposes of this study, serious device-related adverse events are defined as serious device-related adverse events as adjudicated by the Clinical Events Committee.
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A revision is a procedure that adjusts or in any way modifies or removes part of the original implant configuration, with or without replacement of a component. A revision may also include adjusting the position of the original configuration.
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A removal is a procedure where the entire original system configuration is removed with or without replacement.
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A re-operation is any surgical procedure at the involved level(s) that does not include removal, modification, or addition of any components to the system.
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A supplemental fixation is a spinal procedure in which additional instrumentation not under study in the protocol is implanted (e.g., supplemental placement of a rod/screw system or a plate/screw system). In addition, any subsequent procedures related to the index level should be reported. This would include posterior fusion, leaving or removing a motion retaining device in place, decompression, facet rhizotomy, etc at the same, adjacent or distant levels.
Powered Secondary Endpoints
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Back Pain, measured at rest using a visual analog scale (VAS); improvement of 20 mm or more on a 100 mm VAS scale at 24 months compared to baseline will be considered clinically significant.
-
Leg Pain, measured at rest using a visual analog scale (VAS). The success rate will be formally tested for superiority in the Activ-L group. A patient will be considered a responder if, at the 24 month visit they achieve at least a 20 mm VAS improvement in the leg with the maximum pain at baseline, with no worsening in the other leg.
Unpowered Secondary Endpoints
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The mean Oswestry Disability Index score, as well as the mean improvement, will be compared between groups across all study visits. The incidence of both 15% and 15 point improvements will also be compared.
-
Quality of Life, measured using the Short Form-36 Questionnaire (SF-36); improvement of 15% in the overall score at 24 months compared to baseline will be considered clinically significant.
-
Disc height (incidence of 3 mm change), as measured by standard lateral radiograph. Comparison of disc height to the 6-week height will also be performed to account for the expected degree of immediate post-operative "settling" of the prosthesis.
-
Incidence of subsidence of the device (> 3 mm) at the 24-month visit.
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Neurological status at 24 months compared to baseline.
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The mean operative time.
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Safety: The individual incidence rates of all adverse events through 24 months follow-up.
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Each subject will remain in the study for 5 years post treatment. It is expected to take 6 years to collect all required data for this study.
Power Analysis
Sample Size Group 1 | Sample Size Group 2 | Group 1 or Treatment | Group 2 or Control | Diff if H0 | Diff if H1 | |||
---|---|---|---|---|---|---|---|---|
Power | N1 | N2 | P1.1 | P2 | D0 | D1 | Target Alpha | Beta |
0.8000 | 178 | 89 | 0.6771 | 0.5000 | 0.0000 | 0.1771 | 0.0500 | 0.2000 |
0.8000 | 178 | 89 | 0.7227 | 0.5500 | 0.0000 | 0.1727 | 0.0500 | 0.2000 |
0.8000 | 178 | 89 | 0.7665 | 0.6000 | 0.0000 | 0.1665 | 0.0500 | 0.2000 |
0.8000 | 178 | 89 | 0.8086 | 0.6500 | 0.0000 | 0.1586 | 0.0500 | 0.2000 |
0.8000 | 178 | 89 | 0.8487 | 0.7000 | 0.0000 | 0.1487 | 0.0500 | 0.2000 |
0.8000 | 178 | 89 | 0.8865 | 0.7500 | 0.0000 | 0.1365 | 0.0500 | 0.2000 |
0.8000 | 178 | 89 | 0.9218 | 0.8000 | 0.0000 | 0.1218 | 0.0500 | 0.2000 |
Follow Up Evaluations
-
AP/Lateral, flexion/extension, and side bending standing x-rays
-
Work status
-
VAS Pain assessment (back, right and left leg)
-
Oswestry Disability Index score
-
Quality of life assessment (SF-36)
-
Neurological assessment
-
Adverse events
-
AP/Lateral, flexion/extension, and side bending standing x-rays
-
Work status
-
VAS Pain assessment (back, right and left leg)
-
Oswestry Disability Index score
-
Quality of life assessment (SF-36)
-
Neurological assessment
-
Range of Motion
-
Adverse events
-
AP and Lateral, flexion/extension and lateral bending X-rays
-
Work status
-
VAS Pain assessment (back, right and left leg)
-
Oswestry Disability Index score
-
Quality of life assessment (SF-36)
-
Neurological assessment
-
Pain medication status
-
Range of Motion
-
Subject satisfaction
-
Adverse events