Degenerative Disc Disease
Conditions
Keywords
Degenerative, Disc
Brief summary
The purpose of this study is to learn whether an investigational device called the Activ-L Artificial Disc is safe and effective in the treatment of degenerative disc disease of the lower (lumbar) spine.
Detailed description
The objective of this clinical study is to evaluate the safety and effectiveness of the Activ-L Artificial Disc for treatment of single-level degenerative disc disease of the lumbar spine in patients who have been unresponsive to at least six months of prior conservative care. The hypothesis of the study is that the Activ-L Disc is non-inferior to the control (the Charité® Artificial Disc \[DePuy Spine\] or ProDisc-L® Total Disc Replacement \[Synthes Spine\]) with respect to the rate of individual subject success at 24 months. Individual subject success is a composite of effectiveness and safety.
Interventions
DEVICEActiv-L Artificial Disc
Implantation at one level of the lumbar spine, either L4/L5 or L5/S1.
DEVICEProDisc-L Total Disc Replacement or Charité Artificial Disc
Implantation at one level of the lumbar spine, either L4/L5 or L5/S1.
Sponsors
Aesculap Implant Systems
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 18 - 60, skeletally mature * Symptomatic DDD with objective evidence of lumbar DDD, with any of the following characteristics by MRI scan: * instability as defined by ≥ 3mm translation or ≥ 5° angulation. * osteophyte formation of facet joints or vertebral endplates. * decreased disc height of \>2mm 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. * Single level symptomatic disease at L4/L5 or L5/S1. * six months of unsuccessful conservative treatment * ODI score ≥ 40/100. * Surgical candidate for an anterior approach to the lumbar spine. * Back pain at the operative level only, with or without leg pain. * Back pain VAS score greater than the higher of the two VAS leg pain scores. * VAS back pain score ≥ 40/100 mm. * Willing to return for follow-up visits and sign an Informed Consent and HIPAA Authorization.
Exclusion criteria
* Previous surgery at any lumbar level, except IDET (Intradiscal Electrothermal Annuloplasty), percutaneous nucleoplasty, or microdiscectomy. * Chronic radiculopathy, i.e., 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. * endplate dimensions smaller than 34.5 mm in medial-lateral and/or 27 mm in the anterior-posterior direction * Evidence of significant, symptomatic disc degeneration at another lumbar level. * Preoperative remaining disc height \< 3mm * Myelopathy. * Previous compression or burst fracture at the affected level. * Sequestered herniated nucleus pulposus with migration. * Mid-sagittal stenosis of \<8mm (by MRI). * Degenerative or lytic spondylolisthesis \> 3mm. * Spondylolysis. * Isthmic spondylolisthesis. * Lumbar scoliosis (\> 11 degrees of sagittal plane deformity). * Spinal tumor. * Active systemic infection or infection at the site of surgery. * Facet ankylosis or severe facet degeneration. * Continuing steroid use or prior use for more than 2 months. * History of allergies to any of the device components. * Pregnancy or planning to become pregnant within the next 2 years. * Morbid obesity (BMI \>35). * Investigational drug or device use within 30 days. * Osteoporosis or osteopenia * Metabolic bone disease. * Leg pain with migrated sequestrum fragment. * History of rheumatoid arthritis, lupus, or other autoimmune disorder. * Ankylosing spondylitis. * History of HIV/AIDS or hepatitis that precludes surgery. * History of deep vein thrombosis, symptoms of arterial insufficiency, or thromboembolytic disease. * 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. * Life expectancy \<5 years. * Chemotherapy within past 5 years or any cancer other than non-melanoma skin cancer treated with curative intent within the past 5 years. * Prior nephrectomy. * Abdominal adhesions, endometriosis, inflammatory bowel disease, Crohn's disease, diverticulitis, ulcerative colitis or other abdominal pathology that would preclude abdominal surgical approach. * Insulin-dependent diabetes. * 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. * History of Pelvic Inflammatory Disease. * Peritonitis. * Currently in active spinal litigation as a result of medical negligence. * Prisoner. * Psychiatric or cognitive impairment that would interfere with the subject's ability to comply with the study requirements, e.g., Alzheimer's disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absence of Serious Device Related Adverse Events | 24 months | Percent of subjects demonstrating no device related SAE's at 24 months as per the Clinical Events Committee (CEC) |
| Neurological Success | 24 months | Percent of patients demonstrating maintenance or improvement in combined motor and sensory evaluations at 24 months compared to baseline |
| Overall Success at 24 Months Relative to Baseline | 24 months | Measured by absence of treatment failure; absence or serious device related AE; maintenance or improvement of ROM at index level; maintenance or improvement of neurological status; improvement in ODI score. |
| Device Success | 24 months | Percent of subjects demonstrating no Subsequent Surgical Interventions (SSI's) at the index level (L4-L5 or L5-S1) at 24 months. |
| ODI Success | 24 months | Percent of subjects demonstrating an improvement of greater than or equal to 15 points at 24 months compared to baseline |
| Range of Motion (ROM) Success | 24 months | Percent of subjects demonstrating maintenance or improvement in ROM at 24 months compared to baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ODI Success Using Two Measures of Success | 24 months | Number of subjects demonstrating improvement in two measures of ODI success at 24 months compared to baseline |
| Improvement in SF-36 Scores | 24 months | Number of subjects demonstrating a greater than or equal to 15% improvement in mental (MCS) and physical (PCS) component summary scores at 24 months compared to baseline |
| VAS Success for Back and Leg Pain at Rest | 24 months | Number of patients demonstrating improvement in back and leg pain at 24 months compared to baseline |
Countries
United States
Participant flow
Recruitment details
Subjects were screened and enrolled at 19 US health care center sites
Participants by arm
| Arm | Count |
|---|---|
| Investigational Implantation of the Activ-L Artificial Disc at one level of the lumbar spine, either L4/L5 or L5/S1 | 264 |
| Control Implantation of either the ProDisc Total Disc Replacement or the Charité Artificial Disc at one level of the lumbar spine, either L4/L5 or L5/S1. | 112 |
| Total | 376 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 12 | 9 |
| Overall Study | Non-Randomized Training Subjects | 46 | 6 |
| Overall Study | Physician Decision | 8 | 3 |
| Overall Study | Withdrawal by Subject | 6 | 5 |
Baseline characteristics
| Characteristic | Investigational | Control | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 264 Participants | 112 Participants | 376 Participants |
| Age, Continuous | 39.1 years STANDARD_DEVIATION 8.6 | 40.0 years STANDARD_DEVIATION 8.6 | 39.6 years STANDARD_DEVIATION 8.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 29 Participants | 12 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 235 Participants | 100 Participants | 335 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Normal Neurological Status Motor | 97 participants | 40 participants | 137 participants |
| Normal Neurological Status Reflexes | 91 participants | 42 participants | 133 participants |
| Normal Neurological Status Sensory | 78 participants | 33 participants | 111 participants |
| Oswestry Disability Index (ODI) Scores for Low Back Pain | 57.1 units on a scale STANDARD_DEVIATION 13.9 | 58.6 units on a scale STANDARD_DEVIATION 14.1 | 57.9 units on a scale STANDARD_DEVIATION 13.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants | 5 Participants | 23 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) White | 233 Participants | 106 Participants | 339 Participants |
| Rotational Range of Motion Flexion/Extension | 6.6 degrees STANDARD_DEVIATION 5.1 | 6.6 degrees STANDARD_DEVIATION 4.6 | 6.6 degrees STANDARD_DEVIATION 4.8 |
| Rotational Range of Motion Lateral Bending AP | 1.0 degrees STANDARD_DEVIATION 2 | 1.0 degrees STANDARD_DEVIATION 1.8 | 1.0 degrees STANDARD_DEVIATION 1.9 |
| Sex: Female, Male Female | 124 Participants | 56 Participants | 180 Participants |
| Sex: Female, Male Male | 140 Participants | 56 Participants | 196 Participants |
| Short-Form (36) Health Questionnaire (SF-36) Scores SF-36 MCS | 39.1 units on a scale STANDARD_DEVIATION 13.9 | 39.6 units on a scale STANDARD_DEVIATION 14.9 | 39.4 units on a scale STANDARD_DEVIATION 14.4 |
| Short-Form (36) Health Questionnaire (SF-36) Scores SF-36 PCS | 29.9 units on a scale STANDARD_DEVIATION 6.2 | 28.4 units on a scale STANDARD_DEVIATION 6.2 | 29.2 units on a scale STANDARD_DEVIATION 6.2 |
| Translational Range of Motion | 0.5 millimeters STANDARD_DEVIATION 0.7 | 0.6 millimeters STANDARD_DEVIATION 0.6 | 0.6 millimeters STANDARD_DEVIATION 0.6 |
| Visual Analog Scale (VAS) Ratings for Back and Leg Pain VAS Back Pain | 79.0 units on a scale STANDARD_DEVIATION 14.9 | 79.1 units on a scale STANDARD_DEVIATION 14.8 | 79.1 units on a scale STANDARD_DEVIATION 14.8 |
| Visual Analog Scale (VAS) Ratings for Back and Leg Pain VAS Left Leg Pain | 29.6 units on a scale STANDARD_DEVIATION 29.4 | 30.7 units on a scale STANDARD_DEVIATION 29.5 | 30.4 units on a scale STANDARD_DEVIATION 29.6 |
| Visual Analog Scale (VAS) Ratings for Back and Leg Pain VAS Right Leg Pain | 28.7 units on a scale STANDARD_DEVIATION 29.8 | 32.9 units on a scale STANDARD_DEVIATION 29.6 | 30.6 units on a scale STANDARD_DEVIATION 30 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 197 / 218 | 100 / 106 |
| serious Total, serious adverse events | 86 / 218 | 57 / 106 |
Outcome results
Primary
Absence of Serious Device Related Adverse Events
Percent of subjects demonstrating no device related SAE's at 24 months as per the Clinical Events Committee (CEC)
Time frame: 24 months
Population: Intent to treat population; missing data imputed as failures
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Investigational | Absence of Serious Device Related Adverse Events | 76.6 percentage of participants |
| Control | Absence of Serious Device Related Adverse Events | 70.8 percentage of participants |
Primary
Device Success
Percent of subjects demonstrating no Subsequent Surgical Interventions (SSI's) at the index level (L4-L5 or L5-S1) at 24 months.
Time frame: 24 months
Population: Intent to treat population; missing data imputed as failures
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Investigational | Device Success | 84.4 percentage of participants |
| Control | Device Success | 84.9 percentage of participants |
Primary
Neurological Success
Percent of patients demonstrating maintenance or improvement in combined motor and sensory evaluations at 24 months compared to baseline
Time frame: 24 months
Population: Intent to treat population; missing data imputed as failures
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Investigational | Neurological Success | 80.3 percentage of participants |
| Control | Neurological Success | 76.4 percentage of participants |
Primary
ODI Success
Percent of subjects demonstrating an improvement of greater than or equal to 15 points at 24 months compared to baseline
Time frame: 24 months
Population: Intent to treat population; missing data imputed as failures
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Investigational | ODI Success | 75.2 percentage of participants |
| Control | ODI Success | 66.0 percentage of participants |
Primary
Overall Success at 24 Months Relative to Baseline
Measured by absence of treatment failure; absence or serious device related AE; maintenance or improvement of ROM at index level; maintenance or improvement of neurological status; improvement in ODI score.
Time frame: 24 months
Population: Intent to treat population; missing data imputed as failures
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Investigational | Overall Success at 24 Months Relative to Baseline | Including ROM success component | 42.2 percentage of participants |
| Investigational | Overall Success at 24 Months Relative to Baseline | Without ROM success component | 61.9 percentage of participants |
| Control | Overall Success at 24 Months Relative to Baseline | Including ROM success component | 28.3 percentage of participants |
| Control | Overall Success at 24 Months Relative to Baseline | Without ROM success component | 52.8 percentage of participants |
p-value: <0.05t-test, 1 sided
Primary
Range of Motion (ROM) Success
Percent of subjects demonstrating maintenance or improvement in ROM at 24 months compared to baseline
Time frame: 24 months
Population: Intent to treat population; missing data imputed as failures
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Investigational | Range of Motion (ROM) Success | 58.7 percentage of participants |
| Control | Range of Motion (ROM) Success | 42.5 percentage of participants |
Secondary
Improvement in SF-36 Scores
Number of subjects demonstrating a greater than or equal to 15% improvement in mental (MCS) and physical (PCS) component summary scores at 24 months compared to baseline
Time frame: 24 months
Population: Intent to treat population; observational data (i.e. missing data not imputed as failures)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Investigational | Improvement in SF-36 Scores | SF-36 MCS | 101 participants |
| Investigational | Improvement in SF-36 Scores | SF-36 PCS | 156 participants |
| Control | Improvement in SF-36 Scores | SF-36 MCS | 48 participants |
| Control | Improvement in SF-36 Scores | SF-36 PCS | 69 participants |
Secondary
ODI Success Using Two Measures of Success
Number of subjects demonstrating improvement in two measures of ODI success at 24 months compared to baseline
Time frame: 24 months
Population: Intent to treat population; observational data (i.e. missing data not imputed as failures)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Investigational | ODI Success Using Two Measures of Success | Greater than or equal to 15 points of improvement | 164 participants |
| Investigational | ODI Success Using Two Measures of Success | Greater than or equal to 15% improvement | 170 participants |
| Control | ODI Success Using Two Measures of Success | Greater than or equal to 15 points of improvement | 70 participants |
| Control | ODI Success Using Two Measures of Success | Greater than or equal to 15% improvement | 77 participants |
Secondary
VAS Success for Back and Leg Pain at Rest
Number of patients demonstrating improvement in back and leg pain at 24 months compared to baseline
Time frame: 24 months
Population: Intent to treat population; observed data (i.e. missing data not imputed as failures)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Investigational | VAS Success for Back and Leg Pain at Rest | VAS Rating for Left Leg Pain | 72 participants |
| Investigational | VAS Success for Back and Leg Pain at Rest | VAS Rating for Right Leg Pain | 73 participants |
| Investigational | VAS Success for Back and Leg Pain at Rest | VAS Rating for Back Pain | 162 participants |
| Control | VAS Success for Back and Leg Pain at Rest | VAS Rating for Back Pain | 72 participants |
| Control | VAS Success for Back and Leg Pain at Rest | VAS Rating for Left Leg Pain | 35 participants |
| Control | VAS Success for Back and Leg Pain at Rest | VAS Rating for Right Leg Pain | 36 participants |