Chronic Low-Back Pain, Neuropathic Pain, Refractory Pain
Conditions
Keywords
Chronic Low Back Pain, Spinal Cord Stimulation
Brief summary
The objective of this study is to evaluate the efficacy of BurstDR dorsal column stimulation, compared with conventional medical management, in improving pain and back-related physical function in subjects suffering with chronic, refractory axial low back pain with a neuropathic component, who have not had lumbar spine surgery and for whom surgery is not an option.
Detailed description
A prospective, multi-center, randomized, controlled clinical study with an optional crossover component. The study is designed to evaluate the efficacy of BurstDR SCS in the treatment of chronic axial low back pain with a neuropathic component, compared to conventional medical management (CMM). Subjects will be followed in-clinic at 1,3, 6, 9, 12, 18 and 24 months and via phone call or optional clinic visit at 15- and 21-months. The primary endpoint will be assessed at the 6-month follow-up visit. Upon completion of the 6-month follow-up visit, subjects who are dissatisfied with therapy and receiving inadequate improvement with their treatment assignment will be allowed to cross-over to the other treatment arm, if desired. The study will enroll up to 270 patients at up to 30 sites. Subjects will be randomized in a 3:2 fashion to yield approximately 200 evaluable subjects for the primary endpoint analysis.
Interventions
DEVICESpinal Cord Stimulation
Utilization of BURSTDR stimulation
Assessing type of CMM, location and frequency.
Sponsors
Abbott Medical Devices
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Patient must be willing and able to provide written informed consent prior to any clinical investigation-related procedure. 2. Age ≥ 18 years 3. Patient has chronic (at least 6 months), refractory axial low back pain with a neuropathic component and is not a candidate for spine surgery 4. Patient has back pain for ≥ 6 months inadequately responsive to supervised conservative care 5. Patient has not had spine surgery for back or leg pain 6. Patient is a candidate for spinal cord stimulation 7. Low back pain ≥ 6 on Numerical Rating Scale 8. Oswestry Disability Index score of ≥ 30% 9. Willing and able to comply with the instructions for use, operate the study device, and comply with this Clinical Investigation Plan
Exclusion criteria
1. Pathology seen on imaging tests obtained within the past 12 months that is clearly identified and is likely the cause of the CLBP, that can be addressed with surgery. 2. Primary complaint of leg pain, or leg pain is greater than back pain 3. Back pain is due to any of the following: * spinal instability defined as \> 2 mm translation on radiographic imaging * visceral causes (e.g., endometriosis or fibroids) * vascular causes (e.g., aortic aneurysm) * spinal infection (e.g., osteomyelitis) * inflammation or damage to the spinal cord (e.g. arachnoiditis or syringomyelia) * tumor or spinal metastases 4. Has widespread pain (e.g. fibromyalgia) or pain in other area(s), not intended to be treated in this study (e.g. neck pain, shoulder pain) 5. Patient has seronegative spondyloarthropathy (e.g. rheumatoid, lupus, psoriatic) 6. Neurological deficit (e.g. foot drop) 7. Prior lumbar spine surgery or sacroiliac joint fusion 8. Patient has used a morphine equivalent daily dose of more than 50 MME in the last 30 days 9. Patient is bed bound 10. Patients with regular intake of systemic steroids (except inhaled steroids used to treat asthma) 11. Imaging (MRI, CT, X-ray) findings within the last 12 months that contraindicates lead placement 12. Known allergic reaction to implanted materials 13. Severe scoliotic deformity (\>11 degrees in thoracic or lumbar spine) 14. Patient has a history of, or existing intrathecal drug pump 15. Patient has previous experience with neuromodulation devices, including a failed trial 16. BMI \> 40 17. Patient is enrolled, or intends to participate, in another clinical drug and/or device study or registry that may interfere with the results of this study, as determined by Abbott personnel 18. Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical investigation or to comply with follow-up requirements of the clinical investigation results. 19. Failed psychological evaluation 20. Suspicion or evidence of untreated mental illness, or substance abuse 21. Patient demonstrated 2 or more Waddell's signs of nonorganic behavior 22. Patient is in current litigation for back pain/injury, or is currently receiving worker's compensation 23. Pregnant or nursing subjects and those who plan pregnancy during the clinical investigation follow-up period. * Female subjects of child-bearing potential must have a negative pregnancy test done within 7 days prior to enrollment/baseline visit per site standard test.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Difference in Responders Between Both Groups | 6 Months | Improvement in pain, defined as percentage of patients who report a ≥ 50% decrease on Numeric Rating Scale (NRS). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Numerical Rating Scale (NRS) Relative Change From Baseline to 6 Months | Baseline to 6 Months | The numeric rating scale (NRS) is a verbal or written determination of a pain level on a scale from 0 to 10, in which 0 represents no pain and 10 represents excruciating pain (the worst pain imaginable). Lower scores indicate pain reduction. The data is expressed as relative change (%). |
| Oswestry Disability Index (ODI) Change From Baseline to 6 Months | Baseline to 6 Months | The Oswestry Disability Index questionnaire will be completed during selected clinical site visits via the electronic data acquisition portal. These questionnaires will be used for the assessment of study endpoints. An interpretation of 0% to 20% means minimal disability;21% to 40% means moderate disability; 41% to 60% means severe disability; 61% to 80% means crippled; and 81%-100% means bed-bound patients. Lower scores indicate less disability. |
| Pain Catastrophizing Scale (PCS) Responder Rate | 6 Months | The Pain Catastrophizing Scale questionnaire is a three part question that measures three pain domains: 1. Rumination (e.g. I can´t stop thinking about how much it hurts) 2. Magnification (e.g. I´m afraid that something serious might happen) 3. Helplessness (e.g. There is nothing I can do to reduce the intensity of my pain). The Pain Catastrophizing Scale questionnaire will be completed during selected clinical site visits via the electronic data acquisition portal. These questionnaires will be used for the assessment of study endpoints. The questionnaire includes 13 statements describing different thoughts and feelings that may be associated with pain. Using the scale 0-4 (0- not at all; 1- to a slight degree; 2- to a moderate degree; 3- to a great degree; and 4- all the time), the patients are expected to indicate the degree to which they have these thoughts and feelings when they're experiencing pain. Lower scores indicate less catastrophizing thoughts. |
| Measure of Composite Responder Rate | 6 Months | Composite Responder rate describes percentage of patients who responded on NRS OR ODI improvements (percentage of patients who report at least ≥13 change on ODI from baseline OR a ≥ 50% decrease in NRS from baseline). |
| Patient-Reported Outcomes Measurement Information System (PROMIS-29) Pain Interference Relative Change From Baseline to 6 Months | Baseline to 6 Months | The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the pain interference domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome). Pain Interferences: Normal: \<55; Mild: 55 - 60; Moderate: 60 -70; and Severe: \>70. |
| Patient-Reported Outcomes Measurement Information System (PROMIS-29) Physical Function Relative Change From Baseline to 6 Months | Baseline to 6 Months | The PROMIS-29 physical function sub-scale includes 4 questions. The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the physical function domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., better outcome). Physical function- Normal: \>45; Mild: 40 - 45; Moderate: 30 - 40; and Severe: \>30. |
| Patient Global Impression of Change (PGIC) Responder Rate | 6 Months | PGIC is a 7 point scale depicting a patient's rating of overall improvement. Patients rate their change as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. The percentage of patients who reported very much improved, or much improved, are presented. |
Countries
United States
Participant flow
Recruitment details
The first patient enrolled in July 2020 was screen failed. Post that, the study enrolled the first subject in September, 2020. In total, 269 subjects were randomized at 30 investigational sites: 162 to SCS and 107 to CMM.
Participants by arm
| Arm | Count |
|---|---|
| Spinal Cord Stimulation (SCS) An SCS Trial period followed by SCS Implantation with the Abbott Proclaim XR Implantable Pulse Generator.
Spinal Cord Stimulation: Utilization of BURSTDR stimulation. | 115 |
| Conventional Medical Management (CMM) CMM consists of an array of therapies including, but not limited to structured physical therapy, medications, injections, and complementary and alternative medicine (e.g. acupuncture, massage therapy).
Conventional Medical Management: Assessing type of CMM, location and frequency. | 103 |
| Total | 218 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| After 6 Months | Death | 2 | 0 |
| After 6 Months | IPG/Lead(s) Explanted But Not Replaced | 2 | 4 |
| After 6 Months | Lost to Follow-up | 1 | 1 |
| After 6 Months | Patient's Health Significantly Declined | 0 | 1 |
| After 6 Months | Patient Was Withdrawn Due To Study Timelines | 0 | 1 |
| After 6 Months | Subject Failed To Comply With The Protocol Requirements | 0 | 1 |
| After 6 Months | Subject Had Back Surgery On March 1st | 0 | 1 |
| After 6 Months | Subject Participation Terminated By Investigator | 2 | 2 |
| After 6 Months | Unsuccessful Trial | 0 | 7 |
| After 6 Months | Withdrawal by Subject | 3 | 13 |
| Through 6 Months | Death | 3 | 0 |
| Through 6 Months | Inclusion/Exclusion | 2 | 1 |
| Through 6 Months | IPG/Lead(s) Explanted But Not Replaced | 2 | 0 |
| Through 6 Months | Lost to Follow-up | 3 | 2 |
| Through 6 Months | Patient Diagnosed With Oral Cancer, Needs To Undergo Radiation And Chemo | 0 | 1 |
| Through 6 Months | Subject Became Pregnant | 1 | 1 |
| Through 6 Months | Subject Failed To Comply With The Protocol Requirements | 1 | 0 |
| Through 6 Months | Subject Participation Terminated By Investigator | 12 | 3 |
| Through 6 Months | Unsuccessful Trial | 17 | 0 |
| Through 6 Months | Withdrawal by Subject | 16 | 14 |
| Through 6 Months | Withdrawn At Sponsor's Request | 1 | 0 |
Baseline characteristics
| Characteristic | Spinal Cord Stimulation (SCS) | Conventional Medical Management (CMM) | Total |
|---|---|---|---|
| Age, Continuous | 58.1 years STANDARD_DEVIATION 13 | 59.1 years STANDARD_DEVIATION 12.4 | 58.5 years STANDARD_DEVIATION 12.8 |
| Pain Numeric Rating Scale (NRS) Left Leg | 2.8 scores on a scale STANDARD_DEVIATION 2.7 | 3.0 scores on a scale STANDARD_DEVIATION 2.8 | 3.0 scores on a scale STANDARD_DEVIATION 2.8 |
| Pain Numeric Rating Scale (NRS) Lower Back | 7.7 scores on a scale STANDARD_DEVIATION 1.2 | 7.9 scores on a scale STANDARD_DEVIATION 1.1 | 7.8 scores on a scale STANDARD_DEVIATION 1.2 |
| Pain Numeric Rating Scale (NRS) Right Leg | 2.7 scores on a scale STANDARD_DEVIATION 2.6 | 3.1 scores on a scale STANDARD_DEVIATION 2.8 | 3.0 scores on a scale STANDARD_DEVIATION 2.7 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 7 Participants | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants | 3 Participants | 10 Participants |
| Race/Ethnicity, Customized Declined or Unable to Disclose Due to Local Regulation | 10 Participants | 6 Participants | 16 Participants |
| Race/Ethnicity, Customized More than one race (One subject having both White and Asian race) | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 96 Participants | 84 Participants | 180 Participants |
| Sex: Female, Male Female | 69 Participants | 52 Participants | 121 Participants |
| Sex: Female, Male Male | 46 Participants | 51 Participants | 97 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 162 | 0 / 107 |
| other Total, other adverse events | 17 / 162 | 0 / 107 |
| serious Total, serious adverse events | 7 / 162 | 0 / 107 |
Outcome results
Primary
The Difference in Responders Between Both Groups
Improvement in pain, defined as percentage of patients who report a ≥ 50% decrease on Numeric Rating Scale (NRS).
Time frame: 6 Months
Population: Percentage of patients who reported a 50% decrease in NRS pain score.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Spinal Cord Stimulation (SCS) | The Difference in Responders Between Both Groups | 87 participants |
| Conventional Medical Management (CMM) | The Difference in Responders Between Both Groups | 5 participants |
p-value: <0.0001Two-sided Z-Test
Secondary
Measure of Composite Responder Rate
Composite Responder rate describes percentage of patients who responded on NRS OR ODI improvements (percentage of patients who report at least ≥13 change on ODI from baseline OR a ≥ 50% decrease in NRS from baseline).
Time frame: 6 Months
Population: The number of participants analyzed includes subjects who were available at that time of analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Spinal Cord Stimulation (SCS) | Measure of Composite Responder Rate | 93 participants |
| Conventional Medical Management (CMM) | Measure of Composite Responder Rate | 13 participants |
p-value: <0.0001Two-sided Z-Test
Secondary
Numerical Rating Scale (NRS) Relative Change From Baseline to 6 Months
The numeric rating scale (NRS) is a verbal or written determination of a pain level on a scale from 0 to 10, in which 0 represents no pain and 10 represents excruciating pain (the worst pain imaginable). Lower scores indicate pain reduction. The data is expressed as relative change (%).
Time frame: Baseline to 6 Months
Population: The number of participants analyzed includes subjects who were available at that time of analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Spinal Cord Stimulation (SCS) | Numerical Rating Scale (NRS) Relative Change From Baseline to 6 Months | 69.7 percent change | Standard Deviation 24.9 |
| Conventional Medical Management (CMM) | Numerical Rating Scale (NRS) Relative Change From Baseline to 6 Months | 5.6 percent change | Standard Deviation 21.3 |
p-value: <0.0001Two-sample t-test.
Secondary
Oswestry Disability Index (ODI) Change From Baseline to 6 Months
The Oswestry Disability Index questionnaire will be completed during selected clinical site visits via the electronic data acquisition portal. These questionnaires will be used for the assessment of study endpoints. An interpretation of 0% to 20% means minimal disability;21% to 40% means moderate disability; 41% to 60% means severe disability; 61% to 80% means crippled; and 81%-100% means bed-bound patients. Lower scores indicate less disability.
Time frame: Baseline to 6 Months
Population: The number of participants analyzed includes subjects who were available at that time of analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Spinal Cord Stimulation (SCS) | Oswestry Disability Index (ODI) Change From Baseline to 6 Months | 29.4 units on a scale | Standard Deviation 18.8 |
| Conventional Medical Management (CMM) | Oswestry Disability Index (ODI) Change From Baseline to 6 Months | 0.7 units on a scale | Standard Deviation 13 |
p-value: <0.0001Two-sample t-test.
Secondary
Pain Catastrophizing Scale (PCS) Responder Rate
The Pain Catastrophizing Scale questionnaire is a three part question that measures three pain domains: 1. Rumination (e.g. I can´t stop thinking about how much it hurts) 2. Magnification (e.g. I´m afraid that something serious might happen) 3. Helplessness (e.g. There is nothing I can do to reduce the intensity of my pain). The Pain Catastrophizing Scale questionnaire will be completed during selected clinical site visits via the electronic data acquisition portal. These questionnaires will be used for the assessment of study endpoints. The questionnaire includes 13 statements describing different thoughts and feelings that may be associated with pain. Using the scale 0-4 (0- not at all; 1- to a slight degree; 2- to a moderate degree; 3- to a great degree; and 4- all the time), the patients are expected to indicate the degree to which they have these thoughts and feelings when they're experiencing pain. Lower scores indicate less catastrophizing thoughts.
Time frame: 6 Months
Population: The number of participants analyzed includes subjects who were available at that time of analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Spinal Cord Stimulation (SCS) | Pain Catastrophizing Scale (PCS) Responder Rate | 90 participants |
| Conventional Medical Management (CMM) | Pain Catastrophizing Scale (PCS) Responder Rate | 19 participants |
p-value: <0.0001Two-sided Z-Test
Secondary
Patient Global Impression of Change (PGIC) Responder Rate
PGIC is a 7 point scale depicting a patient's rating of overall improvement. Patients rate their change as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. The percentage of patients who reported very much improved, or much improved, are presented.
Time frame: 6 Months
Population: The number of participants analyzed includes subjects who were available at that time of analysis. PGIC- % of patients who reported very much improved, or much improved.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Spinal Cord Stimulation (SCS) | Patient Global Impression of Change (PGIC) Responder Rate | 77 participants |
| Conventional Medical Management (CMM) | Patient Global Impression of Change (PGIC) Responder Rate | 2 participants |
p-value: <0.0001Two-sided Z-Test
Secondary
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Pain Interference Relative Change From Baseline to 6 Months
The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the pain interference domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome). Pain Interferences: Normal: \<55; Mild: 55 - 60; Moderate: 60 -70; and Severe: \>70.
Time frame: Baseline to 6 Months
Population: The number of participants analyzed includes subjects who were available at that time of analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Spinal Cord Stimulation (SCS) | Patient-Reported Outcomes Measurement Information System (PROMIS-29) Pain Interference Relative Change From Baseline to 6 Months | 17.9 scores on a scale | Standard Deviation 11.3 |
| Conventional Medical Management (CMM) | Patient-Reported Outcomes Measurement Information System (PROMIS-29) Pain Interference Relative Change From Baseline to 6 Months | 0.9 scores on a scale | Standard Deviation 9.3 |
p-value: <0.0001Two-sample t-test.
Secondary
Patient-Reported Outcomes Measurement Information System (PROMIS-29) Physical Function Relative Change From Baseline to 6 Months
The PROMIS-29 physical function sub-scale includes 4 questions. The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the physical function domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., better outcome). Physical function- Normal: \>45; Mild: 40 - 45; Moderate: 30 - 40; and Severe: \>30.
Time frame: Baseline to 6 Months
Population: The number of participants analyzed includes subjects who were available at that time of analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Spinal Cord Stimulation (SCS) | Patient-Reported Outcomes Measurement Information System (PROMIS-29) Physical Function Relative Change From Baseline to 6 Months | 27.8 scores on a scale | Standard Deviation 24.4 |
| Conventional Medical Management (CMM) | Patient-Reported Outcomes Measurement Information System (PROMIS-29) Physical Function Relative Change From Baseline to 6 Months | 1.4 scores on a scale | Standard Deviation 13.6 |
p-value: <0.0001Two-sample t-test.