Degenerative Disc Disease, Spondylolisthesis, Grade 1
Conditions
Brief summary
The purpose of this trial is to demonstrate the safety and effectiveness of the CarboClear Pedicle Screw System, for skeletally mature DDD patients undergoing one level spinal fusion in combination with interbody fusion device, and requiring immediate, rigid, posterior spinal stabilization of the lumbar and/or sacral spine.
Detailed description
A prospective, multi-center, confirmatory, single arm, study. Results of the study will be compared to data from the literature. The CarboClear Pedicle Screw System is designed for use with intervertebral body fusion device and with autogenous and/or allogenic bone graft comprised of cancellous and/or corticocancellous bone graft, using PLIF or TLIF. A total of 55 subjects will participate in the study, with up to 25 patients recruited at sites in Israel and at least 30 patients will be enrolled in US sites. Follow-ups: Radiographic (AP, lateral and flexion/extension X-Rays) and clinical evaluations. Follow-up sessions at 6 weeks, 3 months, 6 months, 12 months, and 24 months postoperatively, and then annually, until the last patient has completed 2-year follow-up.
Interventions
DEVICEImplantation of the CarboClear Pedicle Screw System
Sponsors
CarboFix Orthopedics Inc.
CarboFix Orthopedics Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 72 Years
Healthy volunteers
No
Inclusion criteria
1. Subject has degenerative disc disease (DDD) at one level, from L2 to S1 vertebrae, with up to Grade I spondylolisthesis. DDD is defined as back pain and/or radicular leg pain with degeneration of the disc confirmed by patient history, radiographic studies, and physical examination, with one or more of the following factors (as measured radiographically, either by CT, MRI or plain film, myelography, discography, etc.): * osteophyte formation of facet joints or vertebral endplates; * decreased disc height, on average by \> 2 mm; * scarring/thickening of ligamentum flavum, annulus fibrosis, or facet joint capsule; * herniated nucleus pulposus; * facet joint degeneration/changes; * vacuum phenomenon. 2. Subject is candidate for single level intervertebral fusion, with or without posterolateral fusion, with implantation of intervertebral body fusion device and supplemental fixation. 3. Subject age is between 21 - 72 years, and subject is skeletally mature. 4. Pre-operative low back and/or leg/s pain (debilitating pain that causes a significant disturbance of the routine daily physical activities) ≥ 40 mm on a 100 mm Visual Analogue Scale (VAS). 5. Pre-operative Oswestry Disability Index (ODI) score ≥ 40 percentage-point, indicating at least moderate disability (interpreted as moderate/severe disability). 6. Low back and/or leg/s pain is unresponsive to prior non-surgical management for a minimum of six months. Non-operative treatment includes pain medication, physical therapy and/or injections. 7. Patient must understand and sign the informed consent. 8. Patient is willing and able to meet the proposed follow-up schedule including return to follow-up visits and complete necessary study paperwork. 9. Patient is willing and able to follow the postoperative management program.
Exclusion criteria
1. Previous fusion or fusion attempts, including anterior fusion or posterolateral fusion, at the index level. 2. Previous fusion or fusion attempts at the adjacent levels. 3. Prior decompression procedures that include removal of soft and bone tissue at the index or adjacent levels. 4. Patient is not skeletally mature. 5. Degenerative spondylolisthesis greater than Grade I. 6. Spinal instability at the index level with ≥ 3 mm translation and/or ≥ 5 degrees angulation. Determination of instability will be assessed using flexion/extension lateral view radiographs. 7. Isthmic spondylolisthesis. 8. Radiographically confirmed moderate or severe spinal stenosis with associated neurogenic claudication. Radiographically confirmed moderate/severe stenosis is defined as reduction of ˃50% of central and/or foraminal canal diameter compared to the adjacent uninvolved levels. Neurogenic claudication is leg, groin or buttock pain and/or numbness that worsens with walking or erect posture and is relieved with flexion of the spine. 9. Systemic infection or infection at the site of surgery. 10. Metabolic bone disease, such as osteopenia, osteoporosis, and osteomalacia. A screening Questionnaire for osteoporosis, SCORE (Simple Calculated Osteoporosis Risk Estimation), will be used to screen patients who require a DEXA bone mineral density measurement. If DEXA is required, exclusion will be defined as measured T-score less than or equal to -2.5 (WHO definition). 11. History of Paget's disease or other bone pathologies, whether acquired or congenital, including renal osteodystrophy, untreated or uncontrolled hyperthyrodism, hypothyroidism, hyperparathyroidism, Ehrlers-Danlos-syndrome, osteogenesis imperfecta, achondroplasia, tuberculosis. 12. Personal and/or familial history NF2, and/or spinal tumor. 13. Ankylosing spondylitis. 14. Diffuse idiopathic skeletal hyperostosis (DISH) syndrome. 15. Active hepatitis (viral or serum) or HIV positive, renal failure, systemic lupus erythematosus, or any other significant medical conditions which would substantially increase the risk of surgery. 16. Immune deficiency disease. 17. Patient is receiving immunosuppressive or long-term steroid therapy. 18. Active malignancy or other significant medical comorbidities. 19. All concomitant diseases that can jeopardize the functioning and success of the patient. 20. Allergy to any component of the investigational device, including carbon fiber-reinforced polyetheretherketone (CFR-PEEK), titanium, and tantalum. 21. Pregnancy, or female subject interested in become pregnant during the duration of the study. 22. Current chemical dependency (e.g., drug and/or alcohol abuse, according to DSM-V definition), as well as those with a history of such abuse. 23. Uncontrolled depression, psychosis, or other symptoms of a mental disorder that, in the investigator's opinion, likely would make the subject unable to comply with the study procedures and could affect the study outcome. 24. Treatment with drugs that may interfere with bone metabolism, such as glucocorticosteroids, calcitonin, bisphosphonates, bone therapeutic doses of fluoride, bone therapeutic doses of vitamin D or vitamin D metabolites, and treatment by chemotherapy. 25. Morbid obesity (BMI ≥ 40). 26. Current smokers (including 3 months prior to surgery). 27. Scoliosis, Cobb angle greater than 11°. 28. Vertebral fractures. 29. Severe muscular, neural or vascular diseases that endanger the spinal column. 30. Missing bone structures, due to severely deformed anatomy or congenital anomalies, which make good anchorage of the implant impossible. 31. Paralysis. 32. Current use of other investigational drug or device. 33. The patient is involved in a worker's compensation case or spine-related litigation. 34. The patient is a prisoner.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Neurological Deterioration, Device Related Serious Adverse Events, Additional Surgical Intervention at Index Level. | Throughout the study until 24 months | 1. Worsening in neurological status (motor, sensory, reflex, straight leg raising, and tenderness assessments) and no new permanent neurological deficits present for at least 2 successive visits at or beyond 6 months (out to 24 months); 2. Device-related serious adverse events (SAEs) through 24 months; 3. Subsequent surgical interventions at the index level through 24 months. |
| Fusion: Evaluated Radiographically (by AP, Lateral and Flexion/Extension X-Rays) by Independent Radiographic Core Lab. | 24 months | Fusion was assessed at follow-up visits, starting at 6 months post operation. Fusion is defined as: 1. Angular motion ˂ 3º; AND 2. Translational motion ˂ 3 mm; AND 3. Presence of continuous bridging bone between the involved motion segment, i.e.: * Presence of interbody (between endplates) bridging bone and absence of radiolucency \> 50%; OR * Presence of right posterolateral bridging bone; OR * Presence of left posterolateral bridging bone. |
| Pain (Low Back and/or Leg/s): Assessed Based on Visual Analogue Scale (VAS) Patient Questionnaire | 24 months | Pain was assessed using the Visual Analogue Scale (VAS) preoperatively and at follow-up visits. The scale ranges from 0 mm (No Pain) to 100 mm (Severe Pain). Patients were instructed to draw a single line across the scale at the point that best described their level of pain. Pain improvement was evaluated at each location (i.e., low back, right leg, and left leg) and was defined as a reduction of at least 20 mm on a 100 mm VAS from baseline level at 24 months. Eligible patients experienced preoperative low back and/or leg pain (debilitating pain that significantly disrupted daily physical activities) with a VAS score of ≥40 mm. |
| Function: Assessed by Oswestry Disability Index (ODI) Patient Questionnaire | 24 months | The Oswestry Disability Index (ODI) is a patient-reported questionnaire administered preoperatively and at follow-up visits. The ODI consists of ten questions focusing on pain intensity, personal care, lifting, walking, sitting, standing, sleeping, sex life, social life, and traveling. Each question has six possible responses. The response scale ranges from 0 to 5 points, with a lower score indicating better function and lower pain (0 points for full functionality with no or minimal pain; 5 points for inability to perform the function due to pain). The total ODI score is calculated by summing the individual question scores and dividing the total by the maximum possible score (50 if all questions are answered), yielding a percentage. ODI scores range from 0% to 100%, with lower percentages indicating reduced pain and disability. The functional outcome measure was defined as an improvement of at least 15 points from baseline at 24 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subject's Overall Well-Being: Assessed by 12-Item Short Form Health Survey (SF-12) Patient Questionnaire | 24 months | Subject's overall well-being (quality of life) was assessed preoperatively and at follow-up visits, using the 12-Item Short Form Health Survey (SF-12), which is a multipurpose short-form quality of life instrument with 12 questions selected from the SF-36 Health Survey. SF-12 questionnaire is designed to measure general health status from the patient's point of view. Results are expressed in terms of two meta-scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). The PCS Score is a composite of the Physical Functioning, Role Functioning, Bodily Pain and General Health Scales within the SF-12 instrument. The MCS is a composite of the Vitality, Social Functioning, Role-Emotional and Mental Health Scales within the SF-12 instrument. The SF-12 is a normative based instrument. PCS and MCS are computed using the rating on 12 questions from 0 to 100, where a 0 score indicates the lowest level of health and 100 indicates the highest level. |
| Patient Satisfaction: Assessed Based on VAS Patient Questionnaire. | 24 months | Satisfaction was assessed at postoperative follow-up visits including at 24-month visit, using a 100 mm VAS (the anchor points are Completely Not Satisfied (0 mm) and Completely Satisfied (100 mm)). Pain was assessed using the Visual Analogue Scale (VAS) preoperatively and at follow-up visits. The scale ranges from 0 mm (No Pain) to 100 mm (Severe Pain). Patients were instructed to draw a single line across the scale at the point that best described their level of pain. Pain improvement was evaluated at each location (i.e., low back, right leg, and left leg) and was defined as a reduction of at least 20 mm on a 100 mm VAS from baseline level at 24 months. |
| Operation Time [Min] | During operation (skin-to-skin) | Operation time (skin-to-skin) was recorded for each subject. |
| Blood Loss During Operation [ml] | During operation (skin to skin) | The volume of blood loss during operation was recorded for each subject. |
Countries
Israel, United States
Participant flow
Recruitment details
The single arm study was approved for a total of 55 subjects, and was conducted at 5 US sites and 3 Israeli sites.
Pre-assignment details
A one arm study (no assignment to groups)
Participants by arm
| Arm | Count |
|---|---|
| CarboClear Pedicle Screw System (Single Arm Study) Patients with Degenerative Disc Disease (DDD) at one level (L2-S1), aged 21-71 years, who have failed to improve with conservative treatment with at least 6 months prior to enrolment.
Implantation of the CarboClear Pedicle Screw System and interbody spinal fusion using an FDA cleared PEEK interbody fusion device (PLIF or TLIF approach); and posterolateral spinal fusion at the physician's discretion | 57 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 2 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Protocol Violation | 4 |
Baseline characteristics
| Characteristic | CarboClear Pedicle Screw System (Single Arm Study) |
|---|---|
| Age, Customized Age | 55.16 years STANDARD_DEVIATION 12.9 |
| Function using Oswestry Disability Index (ODI) | 57.71 units on a scale STANDARD_DEVIATION 12.14 |
| Indications DDD | 1 Participants |
| Indications DDD + Mild Stenosis (< 50%) | 2 Participants |
| Indications DDD + Spondylolisthesis up to Grade I | 1 Participants |
| Indications DDD + Spondylolisthesis up to Grade I + Mild Stenosis (< 50%) | 53 Participants |
| Pain using Visual Analogue Scale (VAS) Left Leg Pain (VAS) | 56.32 units on a scale STANDARD_DEVIATION 37.45 |
| Pain using Visual Analogue Scale (VAS) Lower Back Pain (VAS) | 81.83 units on a scale STANDARD_DEVIATION 17.6 |
| Pain using Visual Analogue Scale (VAS) Right Leg Pain (VAS) | 61.80 units on a scale STANDARD_DEVIATION 34.97 |
| Race/Ethnicity, Customized African | 2 Participants |
| Race/Ethnicity, Customized Caucasian | 55 Participants |
| Region of Enrollment Israel | 26 participants |
| Region of Enrollment United States | 31 participants |
| Sex: Female, Male Female | 34 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 57 |
| other Total, other adverse events | 0 / 57 |
| serious Total, serious adverse events | 7 / 57 |
Outcome results
Primary
Function: Assessed by Oswestry Disability Index (ODI) Patient Questionnaire
The Oswestry Disability Index (ODI) is a patient-reported questionnaire administered preoperatively and at follow-up visits. The ODI consists of ten questions focusing on pain intensity, personal care, lifting, walking, sitting, standing, sleeping, sex life, social life, and traveling. Each question has six possible responses. The response scale ranges from 0 to 5 points, with a lower score indicating better function and lower pain (0 points for full functionality with no or minimal pain; 5 points for inability to perform the function due to pain). The total ODI score is calculated by summing the individual question scores and dividing the total by the maximum possible score (50 if all questions are answered), yielding a percentage. ODI scores range from 0% to 100%, with lower percentages indicating reduced pain and disability. The functional outcome measure was defined as an improvement of at least 15 points from baseline at 24 months.
Time frame: 24 months
Population: Function (ODI) data is available at 24 months for 45 patients who attended 24-month visit and for whom function assessment is available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CarboClear Pedicle Screw System (Single Arm Study) | Function: Assessed by Oswestry Disability Index (ODI) Patient Questionnaire | 34.39 score on a scale | Standard Deviation 21.43 |
Primary
Fusion: Evaluated Radiographically (by AP, Lateral and Flexion/Extension X-Rays) by Independent Radiographic Core Lab.
Fusion was assessed at follow-up visits, starting at 6 months post operation. Fusion is defined as: 1. Angular motion ˂ 3º; AND 2. Translational motion ˂ 3 mm; AND 3. Presence of continuous bridging bone between the involved motion segment, i.e.: * Presence of interbody (between endplates) bridging bone and absence of radiolucency \> 50%; OR * Presence of right posterolateral bridging bone; OR * Presence of left posterolateral bridging bone.
Time frame: 24 months
Population: 24-month radiographic data is available for 49 patients (for patients that attended the 24-month visit, or for non-attendees for whom data is available from earlier visits (e.g., where fusion was confirmed).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CarboClear Pedicle Screw System (Single Arm Study) | Fusion: Evaluated Radiographically (by AP, Lateral and Flexion/Extension X-Rays) by Independent Radiographic Core Lab. | 42 Participants |
Primary
Pain (Low Back and/or Leg/s): Assessed Based on Visual Analogue Scale (VAS) Patient Questionnaire
Pain was assessed using the Visual Analogue Scale (VAS) preoperatively and at follow-up visits. The scale ranges from 0 mm (No Pain) to 100 mm (Severe Pain). Patients were instructed to draw a single line across the scale at the point that best described their level of pain. Pain improvement was evaluated at each location (i.e., low back, right leg, and left leg) and was defined as a reduction of at least 20 mm on a 100 mm VAS from baseline level at 24 months. Eligible patients experienced preoperative low back and/or leg pain (debilitating pain that significantly disrupted daily physical activities) with a VAS score of ≥40 mm.
Time frame: 24 months
Population: VAS pain data is available at 24 months for 45 patients who attended 24-month visit and for whom VAS assessment is available.~Analysis is presented for patients with preoperative pain VAS score ≥40 (in accordance with the clinical investigational plan).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CarboClear Pedicle Screw System (Single Arm Study) | Pain (Low Back and/or Leg/s): Assessed Based on Visual Analogue Scale (VAS) Patient Questionnaire | Pain Improvement (VAS) - Right Leg | 58.11 score on a scale | Standard Deviation 35.46 |
| CarboClear Pedicle Screw System (Single Arm Study) | Pain (Low Back and/or Leg/s): Assessed Based on Visual Analogue Scale (VAS) Patient Questionnaire | Pain Improvement (VAS) - Left Leg | 59.06 score on a scale | Standard Deviation 32.99 |
| CarboClear Pedicle Screw System (Single Arm Study) | Pain (Low Back and/or Leg/s): Assessed Based on Visual Analogue Scale (VAS) Patient Questionnaire | Pain Improvement (VAS) - Low Back | 58.52 score on a scale | Standard Deviation 31.89 |
Primary
Safety: Neurological Deterioration, Device Related Serious Adverse Events, Additional Surgical Intervention at Index Level.
1. Worsening in neurological status (motor, sensory, reflex, straight leg raising, and tenderness assessments) and no new permanent neurological deficits present for at least 2 successive visits at or beyond 6 months (out to 24 months); 2. Device-related serious adverse events (SAEs) through 24 months; 3. Subsequent surgical interventions at the index level through 24 months.
Time frame: Throughout the study until 24 months
Population: All subjects that completed the study the study
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CarboClear Pedicle Screw System (Single Arm Study) | Safety: Neurological Deterioration, Device Related Serious Adverse Events, Additional Surgical Intervention at Index Level. | Neurological deterioration | 3 Participants |
| CarboClear Pedicle Screw System (Single Arm Study) | Safety: Neurological Deterioration, Device Related Serious Adverse Events, Additional Surgical Intervention at Index Level. | Subsequent surgical interventions at the index level | 4 Participants |
| CarboClear Pedicle Screw System (Single Arm Study) | Safety: Neurological Deterioration, Device Related Serious Adverse Events, Additional Surgical Intervention at Index Level. | Device related serious adverse events | 0 Participants |
Secondary
Blood Loss During Operation [ml]
The volume of blood loss during operation was recorded for each subject.
Time frame: During operation (skin to skin)
Population: All 55 patients that participated in the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CarboClear Pedicle Screw System (Single Arm Study) | Blood Loss During Operation [ml] | 212.64 milliliter | Standard Deviation 127.9 |
Secondary
Operation Time [Min]
Operation time (skin-to-skin) was recorded for each subject.
Time frame: During operation (skin-to-skin)
Population: All 55 patients that participated in the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CarboClear Pedicle Screw System (Single Arm Study) | Operation Time [Min] | 135.20 minutes | Standard Deviation 73.38 |
Secondary
Patient Satisfaction: Assessed Based on VAS Patient Questionnaire.
Satisfaction was assessed at postoperative follow-up visits including at 24-month visit, using a 100 mm VAS (the anchor points are Completely Not Satisfied (0 mm) and Completely Satisfied (100 mm)). Pain was assessed using the Visual Analogue Scale (VAS) preoperatively and at follow-up visits. The scale ranges from 0 mm (No Pain) to 100 mm (Severe Pain). Patients were instructed to draw a single line across the scale at the point that best described their level of pain. Pain improvement was evaluated at each location (i.e., low back, right leg, and left leg) and was defined as a reduction of at least 20 mm on a 100 mm VAS from baseline level at 24 months.
Time frame: 24 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CarboClear Pedicle Screw System (Single Arm Study) | Patient Satisfaction: Assessed Based on VAS Patient Questionnaire. | 81.19 score on a scale | Standard Deviation 32.2 |
Secondary
Subject's Overall Well-Being: Assessed by 12-Item Short Form Health Survey (SF-12) Patient Questionnaire
Subject's overall well-being (quality of life) was assessed preoperatively and at follow-up visits, using the 12-Item Short Form Health Survey (SF-12), which is a multipurpose short-form quality of life instrument with 12 questions selected from the SF-36 Health Survey. SF-12 questionnaire is designed to measure general health status from the patient's point of view. Results are expressed in terms of two meta-scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). The PCS Score is a composite of the Physical Functioning, Role Functioning, Bodily Pain and General Health Scales within the SF-12 instrument. The MCS is a composite of the Vitality, Social Functioning, Role-Emotional and Mental Health Scales within the SF-12 instrument. The SF-12 is a normative based instrument. PCS and MCS are computed using the rating on 12 questions from 0 to 100, where a 0 score indicates the lowest level of health and 100 indicates the highest level.
Time frame: 24 months
Population: Out of the patients attended the 24-month visit, 43 patients had SF-12 assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CarboClear Pedicle Screw System (Single Arm Study) | Subject's Overall Well-Being: Assessed by 12-Item Short Form Health Survey (SF-12) Patient Questionnaire | SF-12 PCS Change | 14.50 score on a scale | Standard Deviation 14.45 |
| CarboClear Pedicle Screw System (Single Arm Study) | Subject's Overall Well-Being: Assessed by 12-Item Short Form Health Survey (SF-12) Patient Questionnaire | SF-12 MCS Change | 10.45 score on a scale | Standard Deviation 13.9 |