Degeneration of Lumbar Intervertebral Disc
Conditions
Brief summary
The chronOS Strip is a synthetic bone void filler manufactured from chronOS beta-tricalcium phosphate (β-TCP) granules and a resorbable polymer \[poly(lactide co-ε-caprolactone)\]. The chronOS Strip, combined with autogenous bone and/or bone marrow or autograft, is intended to be used in the spine for posterolateral fusion. The purpose of this prospective, multi-center clinical case series was to evaluate posterolateral fusion rates in a prospective series of patients with degenerative disc disease. The surgical procedure consisted of instrumented posterolateral fusion with interbody support. The chronOS Strip, combined with bone marrow aspirate and local bone, was applied to the posterolateral gutters.
Interventions
DEVICEchronOS Strip
chronOS strip combined with bone marrow aspirate plus local bone
Sponsors
Synthes USA HQ, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Has the following indication for posterolateral fusion (transverse process and facet fusion) with posterior rod and screw fixation: • Degenerative Disc Disease (DDD), with or without stenosis. Diagnosis of DDD requires back and/or leg (radicular) pain along with: 1. Instability (≥ 3 mm translation or ≥ 5° angulation); or 2. MRI confirmation of Modic Type 1 or Type 2 changes; or 3. High intensity zones in the disc space. 2. Has one or two motion segment(s) to be fused between L2 and S1; 3. Skeletally mature adult, at least 18 years of age at the time of surgery; 4. Oswestry Low Back Pain Disability Questionnaire score ≥ 30 (out of 100); 5. Has completed at least 6 months of conservative therapy, which may include physical therapy, bracing, systemic or injected medications; 6. Psychosocially, mentally and physically able to fully comply with this protocol including adhering to scheduled visits, treatment plan, completing forms, and other study procedures; 7. Personally signed and dated informed consent document prior to any study-related procedures indicating that the patient has been informed of all pertinent aspects of the study.
Exclusion criteria
1. Three or more motion segments to be fused; 2. Degenerative scoliosis, defined as Cobb angle \> 10° at any level in lumbar spine; 3. Has had a previous interbody fusion or posterolateral fusion attempt at any level of the lumbar spine; 4. Active systemic or local infection; 5. Known or documented history of communicable disease, including AIDS and HIV; 6. Active Hepatitis (receiving medical treatment within two years); 7. Active rheumatoid arthritis, non-controlled diabetes mellitus, or any other medical condition(s) that would represent a significant increase in surgical risk or interfere with normal healing; 8. Immunologically suppressed, or has received systemic steroids, excluding nasal steroids, at any dose daily for \> 1 month within last 12 months; 9. Known history of Paget's disease, osteomalacia, or any other metabolic bone disease; 10. Osteopenia or Osteoporosis: A screening questionnaire for osteoporosis, SCORE (Simple Calculated Osteoporosis Risk Estimation), will be used to screen patients who require a dual energy x-ray absorptiometry (DXA) bone mineral density measurement. If DXA is required, exclusion will be defined as a DXA bone density measured T score less than or equal to -1.0. 11. Morbid obesity defined as a body mass index \> 40 kg/m2 or weight more than 100 pounds over ideal body weight; 12. Active malignancy. A patient with a history of any invasive malignancy (except non-melanoma skin cancer), unless treated with curative intent and there has been no clinical signs or symptoms of the malignancy for more than 5 years; 13. Current or recent history (within last 2 years) of substance abuse (e.g., recreational drugs, narcotics, or alcohol); 14. Pregnant or planning to become pregnant during study period; 15. Involved in study of another investigational product that may affect outcome; 16. History of psychosocial disorders that could prevent accurate completion of self reporting assessment scales; 17. Patients who are incarcerated.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Posterolateral Fusion Success | Month 24 | The primary outcome for posterolateral fusion status was a composite endpoint incorporating posterior bridging bone status, intersegmental motion (angular and translational motion) and posterior hardware status. To have successful posterolateral fusion, a subject had to be successful in all four components at all levels under investigation. Failure to meet any one of the four components indicated failed posterolateral fusion status. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Oswestry Disability Index (ODI) | Month 24 | The Oswestry Low Back Pain Disability Questionnaire was self-administered to each subject preoperatively and at each clinical follow up examination. Each of the ten questions had six ordered responses coded on a scale from zero to five. The scale ranges from 0-100. A higher score indicates a higher level of disability, and a negative percent change (post surgery minus baseline) indicates improved function. |
| Percent Change in Oswestry Disability Index (ODI) | Month 24 | The Oswestry Low Back Pain Disability Questionnaire was self-administered to each subject preoperatively and at each clinical follow up examination. Each of the ten questions had six ordered responses coded on a scale from zero to five. The scale ranges from 0-100. A higher score indicates a higher level of disability, and a negative percent change (post surgery minus baseline) indicates improved function. Percent change in ODI score was calculated as: \[(Month 24-Baseline)/Baseline\]\*100%. |
| Back Pain on Visual Analog Scale | Month 24 | The subjects completed questionnaires assessing the intensity of pain experienced in the back at the preoperative visit and at all visits postoperatively. Pain intensity was rated on a scale where zero indicated no pain, and 100 represented the worst possible pain. |
| Percent Change in Back Pain on Visual Analog Scale | Month 24 | The subjects completed questionnaires assessing the intensity of pain experienced in the back at the preoperative visit and at all visits postoperatively. Pain intensity was rated on a scale where zero indicated no pain, and 100 represented the worst possible pain. A negative change (post surgery minus baseline) indicated an improvement. Percent change was calculated as: \[(Month 24-Baseline)/Baseline\]\*100%. |
| Percent Change in Leg Pain on Visual Analog Scale | Month 24 | The subjects completed questionnaires assessing the intensity of pain experienced in the leg at the preoperative visit and at all visits postoperatively. Pain intensity was rated on a scale where zero indicated no pain, and 100 represented the worst possible pain. A negative change (post surgery minus baseline) indicated an improvement. Percent change was calculated as: \[(Month 24-Baseline)/Baseline\]\*100%. |
| Short Form 12 (SF-12v2) Physical Component Summary (PCS) | Month 24 | The SF-12v2, comprising 12 questions related to health and wellbeing over the prior four weeks, was administered to subjects preoperatively and at all follow up visits. SF-12v2 represents overall subjective health status by measuring eight health-related parameters (each scored from 0 \[poor health\] to 100 \[better health\]): body pain, general mental health, perception of general health, physical functioning, role limitations caused by mental condition, role limitations caused by a physical condition, social functioning, and vitality. First, the eight scales were standardized using means and standard deviations (SD) for the general US population. Second, PCS was scored by aggregating the eight scales using a standardized algorithm. Finally, PCS was standardized using a linear t-score transformation to have a mean of 50 and a SD of 10 in the general US population (expected range: 13-69). |
| Percent Change in Short Form 12 (SF-12v2) Physical Component Summary (PCS) | Month 24 | The SF-12v2, comprising 12 questions related to health and wellbeing over the prior four weeks, was administered to subjects preoperatively and at all follow up visits. SF-12v2 represents overall subjective health status by measuring eight health-related parameters (each scored from 0 \[poor health\] to 100 \[better health\]): body pain, general mental health, perception of general health, physical functioning, role limitations caused by mental condition, role limitations caused by a physical condition, social functioning, and vitality. First, the eight scales were standardized using means and standard deviations (SD) for the general US population. Second, PCS was scored by aggregating the eight scales using a standardized algorithm. Finally, PCS was standardized using a linear t-score transformation to have a mean of 50 and a SD of 10 in the general US population (expected range: 13-69). Percent change was calculated as \[(Month 24 - Baseline)/Baseline\]\*100%. |
| Short Form 12 (SF-12v2) Mental Component Summary (MCS) | Month 24 | The SF-12v2, comprising 12 questions related to health and wellbeing over the prior four weeks, was administered to subjects preoperatively and at all follow up visits. SF-12v2 represents overall subjective health status by measuring eight health-related parameters (each scored from 0 \[poor health\] to 100 \[better health\]): body pain, general mental health, perception of general health, physical functioning, role limitations caused by mental condition, role limitations caused by a physical condition, social functioning, and vitality. First, the eight scales were standardized using means and standard deviations (SD) for the general US population. Second, MCS was scored by aggregating the eight scales using a standardized algorithm. Finally, MCS was standardized using a linear t-score transformation to have a mean of 50 and a SD of 10 in the general US population (expected range: 10-70). |
| Percent Change in Short Form 12 (SF-12v2) Mental Component Summary (MCS) | Month 24 | The SF-12v2, comprising 12 questions related to health and wellbeing over the prior four weeks, was administered to subjects preoperatively and at all follow up visits. SF-12v2 represents overall subjective health status by measuring eight health-related parameters (each scored from 0 \[poor health\] to 100 \[better health\]): body pain, general mental health, perception of general health, physical functioning, role limitations caused by mental condition, role limitations caused by a physical condition, social functioning, and vitality. First, the eight scales were standardized using means and standard deviations (SD) for the general US population. Second, MCS was scored by aggregating the eight scales using a standardized algorithm. Finally, MCS was standardized using a linear t-score transformation to have a mean of 50 and a SD of 10 in the general US population (expected range: 10-70). Percent change was calculated as \[(Month 24 - Baseline)/Baseline\]\*100%. |
| Leg Pain on Visual Analog Scale | Month 24 | The subjects completed questionnaires assessing the intensity of pain experienced in the leg at the preoperative visit and at all visits postoperatively. Pain intensity was rated on a scale where zero indicated no pain, and 100 represented the worst possible pain. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| chronOS Strip Patients with DDD (with or without stenosis) were treated at one or two contiguous levels between L1 and S1 (inclusive) with interbody fusion and a posterolateral pedicle screw system. The study device (chronOS Strip) was applied to the posterolateral gutters combined with bone marrow aspirate and local bone. | 76 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Dispositioned prior to treatment | 23 |
| Overall Study | Lost to Follow-up | 16 |
| Overall Study | Treated off protocol-protocol violation | 5 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | chronOS Strip |
|---|---|
| Age, Continuous | 50.1 years STANDARD_DEVIATION 10.37 |
| Level(s) treated One-level, L2-3 | 1 participants |
| Level(s) treated One-level, L3-4 | 1 participants |
| Level(s) treated One level, L4-5 | 22 participants |
| Level(s) treated One-level, L5-S1 | 18 participants |
| Level(s) treated Two-level, L3-5 | 8 participants |
| Level(s) treated Two-level, L4-S1 | 26 participants |
| Sex: Female, Male Female | 40 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 34 / 81 |
| serious Total, serious adverse events | 24 / 81 |
Outcome results
Primary
Posterolateral Fusion Success
The primary outcome for posterolateral fusion status was a composite endpoint incorporating posterior bridging bone status, intersegmental motion (angular and translational motion) and posterior hardware status. To have successful posterolateral fusion, a subject had to be successful in all four components at all levels under investigation. Failure to meet any one of the four components indicated failed posterolateral fusion status.
Time frame: Month 24
Population: The primary endpoint was evaluated for the per-protocol population. Of the 55 patients who were evaluated at the Month 24 visit, six patients were missing complete radiographic data needed to evaluate the primary endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| chronOS Strip | Posterolateral Fusion Success | 45 participants |
Secondary
Back Pain on Visual Analog Scale
The subjects completed questionnaires assessing the intensity of pain experienced in the back at the preoperative visit and at all visits postoperatively. Pain intensity was rated on a scale where zero indicated no pain, and 100 represented the worst possible pain.
Time frame: Month 24
Population: Of the 55 subjects who were evaluated at Month 24, two were missing back pain data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| chronOS Strip | Back Pain on Visual Analog Scale | 29.5 units on a scale | Standard Deviation 27.3 |
Secondary
Leg Pain on Visual Analog Scale
The subjects completed questionnaires assessing the intensity of pain experienced in the leg at the preoperative visit and at all visits postoperatively. Pain intensity was rated on a scale where zero indicated no pain, and 100 represented the worst possible pain.
Time frame: Month 24
Population: Per protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| chronOS Strip | Leg Pain on Visual Analog Scale | 21.1 units on a scale | Standard Deviation 28.1 |
Secondary
Oswestry Disability Index (ODI)
The Oswestry Low Back Pain Disability Questionnaire was self-administered to each subject preoperatively and at each clinical follow up examination. Each of the ten questions had six ordered responses coded on a scale from zero to five. The scale ranges from 0-100. A higher score indicates a higher level of disability, and a negative percent change (post surgery minus baseline) indicates improved function.
Time frame: Month 24
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| chronOS Strip | Oswestry Disability Index (ODI) | 20.3 units on a scale | Standard Deviation 17.5 |
Secondary
Percent Change in Back Pain on Visual Analog Scale
The subjects completed questionnaires assessing the intensity of pain experienced in the back at the preoperative visit and at all visits postoperatively. Pain intensity was rated on a scale where zero indicated no pain, and 100 represented the worst possible pain. A negative change (post surgery minus baseline) indicated an improvement. Percent change was calculated as: \[(Month 24-Baseline)/Baseline\]\*100%.
Time frame: Month 24
Population: Back pain was assessed in the per-protocol population. Of the 55 subjects who were evaluated at the Month 24 visit, two were missing data related to back pain.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| chronOS Strip | Percent Change in Back Pain on Visual Analog Scale | -56.6 percent change | Standard Deviation 52.8 |
Secondary
Percent Change in Leg Pain on Visual Analog Scale
The subjects completed questionnaires assessing the intensity of pain experienced in the leg at the preoperative visit and at all visits postoperatively. Pain intensity was rated on a scale where zero indicated no pain, and 100 represented the worst possible pain. A negative change (post surgery minus baseline) indicated an improvement. Percent change was calculated as: \[(Month 24-Baseline)/Baseline\]\*100%.
Time frame: Month 24
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| chronOS Strip | Percent Change in Leg Pain on Visual Analog Scale | -56.4 percent change | Standard Deviation 92.5 |
Secondary
Percent Change in Oswestry Disability Index (ODI)
The Oswestry Low Back Pain Disability Questionnaire was self-administered to each subject preoperatively and at each clinical follow up examination. Each of the ten questions had six ordered responses coded on a scale from zero to five. The scale ranges from 0-100. A higher score indicates a higher level of disability, and a negative percent change (post surgery minus baseline) indicates improved function. Percent change in ODI score was calculated as: \[(Month 24-Baseline)/Baseline\]\*100%.
Time frame: Month 24
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| chronOS Strip | Percent Change in Oswestry Disability Index (ODI) | -61.6 percent change | Standard Deviation 28.7 |
Secondary
Percent Change in Short Form 12 (SF-12v2) Mental Component Summary (MCS)
The SF-12v2, comprising 12 questions related to health and wellbeing over the prior four weeks, was administered to subjects preoperatively and at all follow up visits. SF-12v2 represents overall subjective health status by measuring eight health-related parameters (each scored from 0 \[poor health\] to 100 \[better health\]): body pain, general mental health, perception of general health, physical functioning, role limitations caused by mental condition, role limitations caused by a physical condition, social functioning, and vitality. First, the eight scales were standardized using means and standard deviations (SD) for the general US population. Second, MCS was scored by aggregating the eight scales using a standardized algorithm. Finally, MCS was standardized using a linear t-score transformation to have a mean of 50 and a SD of 10 in the general US population (expected range: 10-70). Percent change was calculated as \[(Month 24 - Baseline)/Baseline\]\*100%.
Time frame: Month 24
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| chronOS Strip | Percent Change in Short Form 12 (SF-12v2) Mental Component Summary (MCS) | 24.1 percent change | Standard Deviation 29 |
Secondary
Percent Change in Short Form 12 (SF-12v2) Physical Component Summary (PCS)
The SF-12v2, comprising 12 questions related to health and wellbeing over the prior four weeks, was administered to subjects preoperatively and at all follow up visits. SF-12v2 represents overall subjective health status by measuring eight health-related parameters (each scored from 0 \[poor health\] to 100 \[better health\]): body pain, general mental health, perception of general health, physical functioning, role limitations caused by mental condition, role limitations caused by a physical condition, social functioning, and vitality. First, the eight scales were standardized using means and standard deviations (SD) for the general US population. Second, PCS was scored by aggregating the eight scales using a standardized algorithm. Finally, PCS was standardized using a linear t-score transformation to have a mean of 50 and a SD of 10 in the general US population (expected range: 13-69). Percent change was calculated as \[(Month 24 - Baseline)/Baseline\]\*100%.
Time frame: Month 24
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| chronOS Strip | Percent Change in Short Form 12 (SF-12v2) Physical Component Summary (PCS) | 17.7 percent change | Standard Deviation 31.4 |
Secondary
Short Form 12 (SF-12v2) Mental Component Summary (MCS)
The SF-12v2, comprising 12 questions related to health and wellbeing over the prior four weeks, was administered to subjects preoperatively and at all follow up visits. SF-12v2 represents overall subjective health status by measuring eight health-related parameters (each scored from 0 \[poor health\] to 100 \[better health\]): body pain, general mental health, perception of general health, physical functioning, role limitations caused by mental condition, role limitations caused by a physical condition, social functioning, and vitality. First, the eight scales were standardized using means and standard deviations (SD) for the general US population. Second, MCS was scored by aggregating the eight scales using a standardized algorithm. Finally, MCS was standardized using a linear t-score transformation to have a mean of 50 and a SD of 10 in the general US population (expected range: 10-70).
Time frame: Month 24
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| chronOS Strip | Short Form 12 (SF-12v2) Mental Component Summary (MCS) | 51.3 units on a scale | Standard Deviation 7.9 |
Secondary
Short Form 12 (SF-12v2) Physical Component Summary (PCS)
The SF-12v2, comprising 12 questions related to health and wellbeing over the prior four weeks, was administered to subjects preoperatively and at all follow up visits. SF-12v2 represents overall subjective health status by measuring eight health-related parameters (each scored from 0 \[poor health\] to 100 \[better health\]): body pain, general mental health, perception of general health, physical functioning, role limitations caused by mental condition, role limitations caused by a physical condition, social functioning, and vitality. First, the eight scales were standardized using means and standard deviations (SD) for the general US population. Second, PCS was scored by aggregating the eight scales using a standardized algorithm. Finally, PCS was standardized using a linear t-score transformation to have a mean of 50 and a SD of 10 in the general US population (expected range: 13-69).
Time frame: Month 24
Population: Per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| chronOS Strip | Short Form 12 (SF-12v2) Physical Component Summary (PCS) | 39.2 units on a scale | Standard Deviation 8 |