Back Pain, Failed Back Surgery Syndrome, Pain in Leg, Unspecified
Conditions
Keywords
FBSS, post laminectomy syndrome, SCS, RCT, back pain
Brief summary
The purpose of this study is to compare the effectiveness of spinal cord stimulation (SCS) using the Medtronic Specify® 5-6-5 multicolumn surgical lead plus optimal medical management (OMM) versus OMM alone in patients suffering from predominant low back pain due to failed back surgery syndrome (FBSS).
Detailed description
The study has a multi-center, prospective, randomized (1:1), open-label, parallel-group design of two alternative treatments: * SCS group (SCS+OMM) * OMM group
Interventions
Spinal Cord Stimulation (SCS) using the Medtronic Specify 5-6-5 multicolumn surgical lead. Subjects will undergo an SCS screening test and, if successful, an implantable neurostimulation system implant. Any SCS group subject not implanted will continue to be treated with OMM and will be followed as part of the SCS group.
The investigator and subject will determine an individual OMM treatment plan, which should include non-investigational pharmacologic agents and/or therapies.
Sponsors
MedtronicNeuro
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Period I (from randomization to 6 months) is the randomized parallel group comparative phase. Day zero for the study is the point of randomization. The randomization ratio is 1:1 (SCS+OMM to OMM). For the SCS+OMM arm, the screening test and/or implant occurred after randomization. Period II (6 to 24 months) is the long-term observational follow-up phase.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* SCS candidate with the Specify 5-6-5 surgical lead * Has FBSS and does not require further surgery (defined as persistent or recurrent low back and leg pain of at least 6 months duration following at least one decompression and/or fusion procedure) * Average low back pain is ≥ 5 as assessed by the baseline NPRS * Average low back pain is greater than leg pain * Subject has persistent moderate to severe low back and leg pain despite other treatments
Exclusion criteria
* Treated with SCS, subcutaneous or peripheral nerve stimulation, an intrathecal drug delivery system, requires back surgery at the location related to his/her original back pain complaint or experimental therapies * Most recent back surgery \< 6 months ago * Low back pain only (no leg pain) * Investigator suspects substance abuse that might confound the study results * Radiographic evidence of instability requiring fusion * Pain relieved completely by lying down * Life expectancy of \< 24 months * Subject is pregnant or planning to become pregnant during the course of the study * Subject is unable to undergo study assessments or complete questionnaires independently
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Compare Proportion of Subjects With ≥50% Reduction in Low Back Pain Intensity Between the Treatment Groups | 6 months post randomization | Compare the proportion of subjects with a ≥50% reduction in low back pain intensity, as measured by the NPRS, from baseline to the end of Period I in the SCS group with that in the OMM group. Subjects reported average low back pain using a 11-point NPRS pain diary (0 = no back pain, 10 = worst low back pain imaginable) two times per day for a 7-day period at baseline and prior to 6-month visit. Percent reduction in low back pain intensity was calculated as average NPRS at (6-month visit - baseline) / baseline. Subjects with ≥50% reduction in average low back pain were considered as responders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare Change in Low Back Pain Intensity, as Measured by the Numeric Pain Rating Scale (NPRS), Between the Treatment Groups | 6 months post randomization | Compare change in low back pain intensity, as measured by the Numeric Pain Rating Scale (NPRS), from baseline to the end of Period I for subjects in the SCS group with that in the OMM group. Subjects reported average low back pain using a 11-point NPRS pain diary (0 = no back pain, 10 = worst low back pain imaginable) two times per day for a 7-day period at baseline and prior to 6-month visit. Change in low back pain intensity is calculated as NPRS at baseline - NPRS at 6-month visit, with a positive change indicated as an improvement. |
| Compare Change in Leg Pain Intensity, as Measured by the NPRS, Between the Treatment Groups | 6 months post randomization | Compare change in leg pain intensity, as measured by the NPRS, from baseline to the end of Period I for subjects in the SCS group with that in the OMM group. Subjects reported average leg pain using a 11-point NPRS pain diary (0 = no back pain, 10 = worst low back pain imaginable) two times per day for a 7-day period at baseline and prior to 6-month visit. Change in leg pain intensity is calculated as NPRS at baseline - NPRS at 6-month visit, with a positive change indicated as an improvement. |
| Compare Change in Functional Disability, as Measured by the Oswestry Disability Index (ODI), Between the Treatment Groups | 6 months post randomization | ODI is a validated questionnaire of 10 subject-reported sections on the ability to perform activities of daily living. These 10 sections are pain intensity, personal care, lifting, walking, sitting, standing, sleeping, sex life (if applicable), social life, and traveling. Each section was scored on a 0 to 5 scale with 0 indicating no limitation of function due to pain and 5 indicating major functional disability due to back pain. A raw ODI score was calculated from the total score of 10 sections (minimum is 0 and maximum is 50). This ODI raw score was then normalized to a scale of 0 to 100, with 0-20 categorized as minimal disability, 20-40 as moderate disability, 40-60 as severe disability, 60-80 as severely disabled, and 80-100 as bed-bound patients. The ODI was assessed at baseline and subsequent scheduled study visits. Change in functional disability is calculated as ODI at baseline - ODI at 6-month visit, with a positive change indicated as an improvement. |
| Compare Change in Quality of Life (QoL), as Measured by the SF-36 Physical Component Summary (PCS), Between the Treatment Groups | 6 months post randomization | The QoL scores were collected using the SF-36 questionnaire, which included the scores in the following 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, mental health. The raw score of 0 represents poor health and 100 represents best health. The Physical Component Summary (PCS) score is a norm based score calculated from the raw scores of these 8 domains with a focus on physical health using 1998 US population. Change in PCS is calculated as PCS at 6-month visit - PCS at baseline, with a positive change indicated as an improvement. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Compare Proportion of Subjects With ≥30% Reduction in Low Back Pain Intensity Between the Treatment Groups | 6 months post randomization | This additional analysis was pre-specified to support the analysis of primary objective. The 30% responder which is defined in the following paragraph was considered as clinical relevant to the SCS therapy in back pain. Compare the proportion of subjects with a ≥30% reduction in low back pain intensity, as measured by the NPRS, from baseline to the end of Period I in the SCS group with that in the OMM group. Subjects reported average low back pain using a 11-point NPRS pain diary (0 = no back pain, 10 = worst low back pain imaginable) two times per day for a 7-day period at baseline and prior to 6-month visit. Percent reduction in low back pain intensity was calculated as average NPRS at (6-month visit - baseline) / baseline. Subjects with ≥30% reduction in average low back pain were considered as 30% responders. |
Countries
Belgium, Canada, Colombia, France, Germany, Netherlands, Spain, United Kingdom, United States
Participant flow
Recruitment details
A total of 278 subjects were recruited between January 2013 and August 2015 from 28 sites in Canada, Colombia, Europe, and US.
Pre-assignment details
A total of 60 subjects didn't meet the inclusion and/or exclusion criteria and discontinued from the study before randomization.
Participants by arm
| Arm | Count |
|---|---|
| SCS + OMM Spinal Cord Stimulation (SCS) using multicolumn surgical lead + Optimal Medical Management (OMM): In addition to the OMM described under the OMM group, subjects underwent an SCS screening test and, if successful, received an INS implant. Any SCS group subject not implanted continued to be treated with OMM and were followed as part of the SCS group. | 110 |
| OMM Alone Optimal Medical Management (OMM) alone: Pain treatment was evaluated, and medical management of subjects' pain was optimized. The investigator and subject determined an individual OMM treatment plan, which should include non-investigational pharmacologic agents (e.g., tricyclic antidepressants, opioid analgesics or tramadol, antiepileptics, or lidocaine) and/or interventional therapies (e.g., therapeutic injections, radiofrequency, acupuncture, and physical therapy) as appropriate. Excluded from OMM is intrathecal drug delivery (IDD), peripheral nerve stimulation (PNS; not an approved indication in the USA), back surgery at the location related to the subject's original back pain complaint and experimental therapies. Data regarding pain treatments implemented during the study were collected to reveal how medical management was optimized. | 108 |
| Total | 218 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period II: 6-24M Long-term Follow-up | Active subjects at the time of posting | 34 | 26 |
| Period II: 6-24M Long-term Follow-up | Adverse Event | 0 | 3 |
| Period II: 6-24M Long-term Follow-up | Death | 1 | 1 |
| Period II: 6-24M Long-term Follow-up | Lost to Follow-up | 3 | 3 |
| Period II: 6-24M Long-term Follow-up | Physician Decision | 3 | 12 |
| Period II: 6-24M Long-term Follow-up | Withdrawal by Subject | 8 | 10 |
| Period I: Randomization to 6 Months | Adverse Event | 1 | 1 |
| Period I: Randomization to 6 Months | Lost to Follow-up | 2 | 0 |
| Period I: Randomization to 6 Months | Physician Decision | 4 | 0 |
| Period I: Randomization to 6 Months | Withdrawal by Subject | 6 | 0 |
Baseline characteristics
| Characteristic | OMM Alone | Total | SCS + OMM |
|---|---|---|---|
| Age, Continuous | 55.1 Years STANDARD_DEVIATION 10.2 | 53.9 Years STANDARD_DEVIATION 11.5 | 52.8 Years STANDARD_DEVIATION 12.5 |
| Region of Enrollment Belgium | 24 Participants | 49 Participants | 25 Participants |
| Region of Enrollment Canada | 4 Participants | 8 Participants | 4 Participants |
| Region of Enrollment Colombia | 4 Participants | 10 Participants | 6 Participants |
| Region of Enrollment France | 13 Participants | 25 Participants | 12 Participants |
| Region of Enrollment Germany | 2 Participants | 4 Participants | 2 Participants |
| Region of Enrollment Netherlands | 6 Participants | 12 Participants | 6 Participants |
| Region of Enrollment Spain | 6 Participants | 11 Participants | 5 Participants |
| Region of Enrollment United Kingdom | 17 Participants | 35 Participants | 18 Participants |
| Region of Enrollment United States | 32 Participants | 64 Participants | 32 Participants |
| Sex: Female, Male Female | 64 Participants | 132 Participants | 68 Participants |
| Sex: Female, Male Male | 44 Participants | 86 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 110 | 0 / 108 |
| other Total, other adverse events | 4 / 110 | 11 / 108 |
| serious Total, serious adverse events | 18 / 110 | 7 / 108 |
Outcome results
Primary
Compare Proportion of Subjects With ≥50% Reduction in Low Back Pain Intensity Between the Treatment Groups
Compare the proportion of subjects with a ≥50% reduction in low back pain intensity, as measured by the NPRS, from baseline to the end of Period I in the SCS group with that in the OMM group. Subjects reported average low back pain using a 11-point NPRS pain diary (0 = no back pain, 10 = worst low back pain imaginable) two times per day for a 7-day period at baseline and prior to 6-month visit. Percent reduction in low back pain intensity was calculated as average NPRS at (6-month visit - baseline) / baseline. Subjects with ≥50% reduction in average low back pain were considered as responders.
Time frame: 6 months post randomization
Population: Intent-to-treat (ITT) - included all randomized subjects and analyzed as randomized, regardless the subjects' status at 6 months. Subjects in the SCS+OMM group received screening tests after the randomization, and might not have proceeded to implant of the neurostimulator. Subjects with missing data at 6 months were imputed as non-responders.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SCS + OMM | Compare Proportion of Subjects With ≥50% Reduction in Low Back Pain Intensity Between the Treatment Groups | 15 Participants |
| OMM Alone | Compare Proportion of Subjects With ≥50% Reduction in Low Back Pain Intensity Between the Treatment Groups | 5 Participants |
p-value: 0.036Z-test using unpooled standard deviation
Secondary
Compare Change in Functional Disability, as Measured by the Oswestry Disability Index (ODI), Between the Treatment Groups
ODI is a validated questionnaire of 10 subject-reported sections on the ability to perform activities of daily living. These 10 sections are pain intensity, personal care, lifting, walking, sitting, standing, sleeping, sex life (if applicable), social life, and traveling. Each section was scored on a 0 to 5 scale with 0 indicating no limitation of function due to pain and 5 indicating major functional disability due to back pain. A raw ODI score was calculated from the total score of 10 sections (minimum is 0 and maximum is 50). This ODI raw score was then normalized to a scale of 0 to 100, with 0-20 categorized as minimal disability, 20-40 as moderate disability, 40-60 as severe disability, 60-80 as severely disabled, and 80-100 as bed-bound patients. The ODI was assessed at baseline and subsequent scheduled study visits. Change in functional disability is calculated as ODI at baseline - ODI at 6-month visit, with a positive change indicated as an improvement.
Time frame: 6 months post randomization
Population: Intent-to-treat (ITT) - included all randomized subjects and analyzed as randomized, regardless the subjects' status at 6 months. Subjects in the SCS+OMM group received screening tests after the randomization, and might not have proceeded to implant of the neurostimulator. Subjects with missing data at 6 months were imputed as having no change.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SCS + OMM | Compare Change in Functional Disability, as Measured by the Oswestry Disability Index (ODI), Between the Treatment Groups | 8.1 units on a scale | Standard Deviation 14.7 |
| OMM Alone | Compare Change in Functional Disability, as Measured by the Oswestry Disability Index (ODI), Between the Treatment Groups | 1.8 units on a scale | Standard Deviation 14.3 |
p-value: <0.001Regression, Linear
Secondary
Compare Change in Leg Pain Intensity, as Measured by the NPRS, Between the Treatment Groups
Compare change in leg pain intensity, as measured by the NPRS, from baseline to the end of Period I for subjects in the SCS group with that in the OMM group. Subjects reported average leg pain using a 11-point NPRS pain diary (0 = no back pain, 10 = worst low back pain imaginable) two times per day for a 7-day period at baseline and prior to 6-month visit. Change in leg pain intensity is calculated as NPRS at baseline - NPRS at 6-month visit, with a positive change indicated as an improvement.
Time frame: 6 months post randomization
Population: Intent-to-treat (ITT) - included all randomized subjects and analyzed as randomized, regardless the subjects' status at 6 months. Subjects in the SCS+OMM group received screening tests after the randomization, and might not have proceeded to implant of the neurostimulator. Subjects with missing data at 6 months were imputed as having no change.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SCS + OMM | Compare Change in Leg Pain Intensity, as Measured by the NPRS, Between the Treatment Groups | 1.2 units on a scale | Standard Deviation 2.1 |
| OMM Alone | Compare Change in Leg Pain Intensity, as Measured by the NPRS, Between the Treatment Groups | -0.1 units on a scale | Standard Deviation 2.4 |
p-value: <0.001Regression, Linear
Secondary
Compare Change in Low Back Pain Intensity, as Measured by the Numeric Pain Rating Scale (NPRS), Between the Treatment Groups
Compare change in low back pain intensity, as measured by the Numeric Pain Rating Scale (NPRS), from baseline to the end of Period I for subjects in the SCS group with that in the OMM group. Subjects reported average low back pain using a 11-point NPRS pain diary (0 = no back pain, 10 = worst low back pain imaginable) two times per day for a 7-day period at baseline and prior to 6-month visit. Change in low back pain intensity is calculated as NPRS at baseline - NPRS at 6-month visit, with a positive change indicated as an improvement.
Time frame: 6 months post randomization
Population: Intent-to-treat (ITT) - included all randomized subjects and analyzed as randomized, regardless the subjects' status at 6 months. Subjects in the SCS+OMM group received screening tests after the randomization, and might not have proceeded to implant of the neurostimulator. Subjects with missing data at 6 months were imputed as having no change.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SCS + OMM | Compare Change in Low Back Pain Intensity, as Measured by the Numeric Pain Rating Scale (NPRS), Between the Treatment Groups | 1.4 units on a scale | Standard Deviation 1.9 |
| OMM Alone | Compare Change in Low Back Pain Intensity, as Measured by the Numeric Pain Rating Scale (NPRS), Between the Treatment Groups | 0.3 units on a scale | Standard Deviation 1.7 |
p-value: <0.001Regression, Linear
Secondary
Compare Change in Quality of Life (QoL), as Measured by the SF-36 Physical Component Summary (PCS), Between the Treatment Groups
The QoL scores were collected using the SF-36 questionnaire, which included the scores in the following 8 domains: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, mental health. The raw score of 0 represents poor health and 100 represents best health. The Physical Component Summary (PCS) score is a norm based score calculated from the raw scores of these 8 domains with a focus on physical health using 1998 US population. Change in PCS is calculated as PCS at 6-month visit - PCS at baseline, with a positive change indicated as an improvement.
Time frame: 6 months post randomization
Population: Intent-to-treat (ITT) - included all randomized subjects and analyzed as randomized, regardless the subjects' status at 6 months. Subjects in the SCS+OMM group received screening tests after the randomization, and might not have proceeded to implant of the neurostimulator. Subjects with missing data at 6 months were imputed as having no change.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SCS + OMM | Compare Change in Quality of Life (QoL), as Measured by the SF-36 Physical Component Summary (PCS), Between the Treatment Groups | 5.27 units on a scale | Standard Deviation 8.28 |
| OMM Alone | Compare Change in Quality of Life (QoL), as Measured by the SF-36 Physical Component Summary (PCS), Between the Treatment Groups | 1.34 units on a scale | Standard Deviation 6.28 |
p-value: <0.001Regression, Linear
Other Pre-specified
Compare Proportion of Subjects With ≥30% Reduction in Low Back Pain Intensity Between the Treatment Groups
This additional analysis was pre-specified to support the analysis of primary objective. The 30% responder which is defined in the following paragraph was considered as clinical relevant to the SCS therapy in back pain. Compare the proportion of subjects with a ≥30% reduction in low back pain intensity, as measured by the NPRS, from baseline to the end of Period I in the SCS group with that in the OMM group. Subjects reported average low back pain using a 11-point NPRS pain diary (0 = no back pain, 10 = worst low back pain imaginable) two times per day for a 7-day period at baseline and prior to 6-month visit. Percent reduction in low back pain intensity was calculated as average NPRS at (6-month visit - baseline) / baseline. Subjects with ≥30% reduction in average low back pain were considered as 30% responders.
Time frame: 6 months post randomization
Population: As-treated - included all randomized subjects who provided data at 6-month visit, and analyzed based on the actual treatment the subjects received at 6-month visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SCS + OMM | Compare Proportion of Subjects With ≥30% Reduction in Low Back Pain Intensity Between the Treatment Groups | 31 Participants |
| OMM Alone | Compare Proportion of Subjects With ≥30% Reduction in Low Back Pain Intensity Between the Treatment Groups | 14 Participants |
p-value: <0.001Z-test using unpooled standard deviation