Chronic Low Back Pain
Conditions
Brief summary
The purpose of this trial is to evaluate the safety and efficacy of ReActiv8 for the treatment of adults with Chronic Low Back Pain when used in conjunction with medical management.
Interventions
DEVICEReActiv8 Implantable Stimulation System (Patient Appropriate Stimulation)
ReActiv8 implanted and configured to deliver stimulation at a patient-appropriate level, and participants instructed to deliver stimulation in two 30-minute sessions per day.
DEVICEReActiv8 Implantable Stimulation System (Low Stimulation)
ReActiv8 implanted and configured to deliver low stimulation, and participants instructed to deliver stimulation in two 30-minute sessions per day.
Sponsors
Mainstay Medical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
22 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥22 years, ≤75 years 2. Chronic Low Back Pain that has persisted \>90 days prior to the baseline visit. 3. Continuing low back pain despite \>90 days of medical management. 4. Qualifying pain score. 5. Qualifying disability score. 6. Evidence of lumbar multifidus muscle dysfunction. 7. Be willing and capable of giving Informed Consent. 8. Ability to comply with the instructions for use and to operate ReActiv8, and to comply with this Clinical Investigation Plan. 9. Suitable for ReActiv8 surgery as determined by the implanting physician prior to inclusion.
Exclusion criteria
1. BMI \> 35 2. Back Pain characteristics: 1. Any surgical correction procedure for scoliosis at any time, or a current clinical diagnosis of scoliosis. 2. Lumbar spine stenosis, as defined by an anterior-posterior diameter of the spinal canal of \<10mm in subjects with lower extremity pain. 3. Neurological deficit possibly associated with the back pain (e.g. foot drop). 4. Back pain due to pelvic or visceral reasons (e.g.: endometriosis or fibroids) or infection (e.g.: post herpetic neuralgia). 5. Back pain due to inflammation or damage to the spinal cord or adjacent structures (e.g. arachnoiditis or syringomyelia). 6. Pathology seen on MRI that is clearly identified and is likely the cause of the CLBP that is amenable to surgery. 7. Back pain due to vascular causes such as aortic aneurysm and dissection. 3. Any current indication for back surgery according to local institutional guidelines, or has indication for back surgery but cannot undergo surgery for other reasons. 4. Leg pain described as being worse than back pain, or radiculopathy (neuropathic pain) below the knee. 5. Source of pain is the sacroiliac joint as determined by the Investigator. 6. Drug use. 7. Surgical and other procedures exclusions. 8. Any prior diagnosis of lumbar vertebral compression fracture, lumbar pars fracture, or lumbar annular tear with disc protrusion that is amenable to surgery. 9. Planned surgery. 10. Co-morbid chronic pain conditions. 11. Other clinical conditions. 12. Psycho-social exclusions. 13. Protocol compliance exclusions. 14. General exclusions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Responder Rate of Low Back Pain With No Increase in Pain Medications | 120 Days | Comparison of responder rates for low back pain VAS between Treatment and Control groups. The Primary Efficacy Endpoint is a comparison of responder rates between Treatment and Control groups, where a responder is a participant with ≥30% reduction from baseline in average low back pain VAS, without any increase from baseline in pain medications and/or muscle relaxants for any reason including non low back pain reasons. The instrument used for evaluating pain is the continuous Visual Analog Scale (VAS) comprised of a horizontal line 10 cm in length, anchored by 2 verbal descriptors, where zero indicates no pain and 10 indicates worst imaginable pain. The value reported is a 7-day average low back pain. Any increase in dosage of a pain medication or any new pain medication taken for any reason counts as an increase in medications. |
| Serious Device and/or Procedure Related Adverse Event Rate | 120 Days | The primary safety assessment is of serious device and/or procedure related adverse events in all participants at 120 days. The 8 events reported below are 6 implant site pocket infections, 1 intra-operative upper airway obstruction, and 1 non-radicular, focal numbness on the surface of the thigh. |
| Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | 120 Days | The CPRA, which was prespecified in the clinical protocol and statistical analysis plan prior to the start of the trial, was performed using the same data as used for the primary endpoint analysis and was included as part of the primary endpoint analysis |
| Mean Change in Low Back Pain VAS | 120 Days | Comparison of change in LBP VAS (120 days from baseline) between the Treatment and Control groups. The instrument used for evaluating pain is the continuous Visual Analog Scale (VAS) comprised of a horizontal line 10 cm in length, anchored by 2 verbal descriptors, where zero indicates no pain and 10 indicates worst imaginable pain. The value reported is a 7-day average low back pain. A change to a lower score (negative value) indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LBP VAS Responder Rate at One Year | 1 Year | A responder is a participant with ≥30% reduction from baseline in average low back pain VAS, without any increase from baseline in pain medications and/or muscle relaxants for any reason including non low back pain reasons. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy. |
| Mean Change in LBP VAS at One Year | 1 Year | Change in LBP VAS at 1 year compared to baseline. The instrument used for evaluating pain is the continuous Visual Analog Scale (VAS) comprised of a horizontal line 10 cm in length, anchored by 2 verbal descriptors, one for each symptom extreme for Low Back Pain. Zero indicates no pain and 10 indicates worst imaginable pain. The value reported is a 7-day average low back pain. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy. A change to a lower score (negative value) indicates improvement. |
| Change in Oswestry Disability Index (ODI) at One Year | 1 Year | Change in ODI at 1 year compared to baseline. ODI is reported as a score from 0 to 100%, where 0%-20% indicates minimal disability, 21%-40% indicates moderate disability, 41%-60% indicates severe disability, 61%-80% indicates crippled, and 81%-100% indicates bedbound or an exaggeration of symptoms. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy. A change to a lower score (negative value) indicates improvement. |
| Change in European Quality of Life Score on Five Dimensions (EQ-5D) at One Year | 1 Year | Change in EQ-5D at 1 year compared to baseline. The EQ-5D Index is scored on a scale of -0.594 to 1.00, with a score of 1.00 indicating full health. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy. A change to a higher score (positive value) indicates improvement. |
| Percent Pain Relief at One Year | 1 Year | PPR is a patient-reported percent of pain relief compared to the pain at baseline, where 0% indicates no pain relief compared to baseline, and 100% indicates complete pain relief compared to baseline. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy. |
| Subject Global Impression of Change (SGIC) at One Year | 1 Year | A questionnaire with the following item: Since I enrolled in the study, my overall status is 1) Very much improved, 2) Much improved, 3) Minimally improved, 4) No change, 5) Minimally worse, 6) Much worse, 7) Very much worse After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy. |
| Resolution of Back Pain at One Year | 1 Year | Resolution of back pain (remitter rate) was defined as a participant with 7-day average low back pain VAS ≤2.5 cm on the 10 cm VAS. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy. |
| Change in Oswestry Disability Index (ODI) | 120 Days | Comparison of change in ODI (120 days from baseline) between Treatment and Control groups. ODI is reported as a score from 0 to 100%, where 0%-20% indicates minimal disability, 21%-40% indicates moderate disability, 41%-60% indicates severe disability, 61%-80% indicates crippled, and 81%-100% indicates bedbound or an exaggeration of symptoms. A change to a lower score (negative value) indicates improvement. |
| Change in European Quality of Life Score on Five Dimensions (EQ-5D) | 120 Days | Comparison of change in EQ-5D (120 days from baseline) between Treatment and Control groups. The EQ-5D Index is scored on a scale of -0.594 to 1.00, with a score of 1.00 indicating full health. A change to a higher score (positive value) indicates improvement. |
| Change in Percent Pain Relief (PPR) | 120 Days | PPR is a patient-reported percent of pain relief at 120 days compared to the pain at baseline, where 0% indicates no pain relief compared to baseline, and 100% indicates complete pain relief compared to baseline. |
| Subject Global Impression of Change (SGIC) | 120 Days | A questionnaire completed with the following item: Since I enrolled in the study, my overall status is 1) Very much improved, 2) Much improved, 3) Minimally improved, 4) No change, 5) Minimally worse, 6) Much worse, 7) Very much worse |
| Resolution of Back Pain (VAS ≤2.5 cm) | 120 Days | Resolution of back pain (remitter rate) was defined as a participant with 7-day average low back pain VAS ≤2.5 cm on the 10 cm VAS. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Opioid Use for Treatment of Low Back Pain at One-Year | 1 Year | Any increase or decrease of dosage or frequency of an opioid taken for the treatment of low back pain was considered a change. |
| Treatment Satisfaction | 120 Days | The Treatment Satisfaction Questionnaire asking the participant if they are satisfied with the treatment. |
| Treatment Satisfaction at One Year | 1 Year | The Treatment Satisfaction Questionnaire asking the participant if they are satisfied with the outcome of the treatment. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy. |
| Supplementary Analysis of Primary Endpoint: Responder Rate of Low Back Pain With No Increase in Low Back Pain Medications | 120 Days | This pre-specified analysis of the primary endpoint examines the impact of rescue medications taken for acute pain conditions for reasons other than low back pain, by excluding those participants from the analysis who took rescue medications for reasons other than low back pain. Nine participants in both groups increased pain medications. In the control group, all nine participants increased pain medications due to low back pain. In the treatment group, three of the nine participants increased pain medications due to low back pain, while six of the nine participants increased pain medications for reasons other than low back pain. Since any increase in pain medications automatically considers a participant a non-responder, these six participants are removed from this analysis to eliminate the confounding factor of increases in pain medications for reasons other than low back pain. |
| Clinical Global Impression of Change at One Year | 1 Year | Clinical Global Impression consists of the following question completed by the Investigator prior to unblinding: In your opinion as a clinician, compared to the patient's situation at baseline, would you say the patient is: 1) Much better, 2) Slightly better, 3) About the same, 4) Slightly worse, 5) Much worse. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy. |
| Clinical Global Impression of Change | 120 Days | Clinical Global Impression consists of the following question completed by the Investigator prior to unblinding: In your opinion as a clinician, compared to the patient's situation at baseline, would you say the patient is: 1) Much better, 2) Slightly better, 3) About the same, 4) Slightly worse, 5) Much worse. |
Countries
Australia, Belgium, Netherlands, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment ReActiv8 Implantable Stimulation System (patient appropriate stimulation): ReActiv8 implanted and configured to deliver stimulation at a patient-appropriate level, and participants instructed to deliver stimulation in two 30-minute sessions per day. | 102 |
| Control/Crossover ReActiv8 Implantable Stimulation System (low stimulation): ReActiv8 implanted and configured to deliver low stimulation, and participants instructed to deliver stimulation in two 30-minute sessions per day.
After the 120-day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. | 102 |
| Total | 204 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 5 |
| Overall Study | Lack of Efficacy | 4 | 4 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Missed Visit | 4 | 3 |
Baseline characteristics
| Characteristic | Treatment | Control/Crossover | Total |
|---|---|---|---|
| Age, Continuous | 46 years STANDARD_DEVIATION 10 | 48 years STANDARD_DEVIATION 9 | 47 years STANDARD_DEVIATION 9 |
| BMI | 28 Kg/m^2 STANDARD_DEVIATION 4 | 28 Kg/m^2 STANDARD_DEVIATION 4 | 28 Kg/m^2 STANDARD_DEVIATION 4 |
| EQ-5D-5L Index Score | 0.572 units on a scale STANDARD_DEVIATION 0.182 | 0.598 units on a scale STANDARD_DEVIATION 0.165 | 0.585 units on a scale STANDARD_DEVIATION 0.174 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 5 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 97 Participants | 95 Participants | 192 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants |
| Evidence of Leg Pain | 32 Participants | 30 Participants | 62 Participants |
| Low Back Pain Medications of Any Type | 77 Participants | 85 Participants | 162 Participants |
| Number of Prior Physical Therapy Sessions | 30 sessions STANDARD_DEVIATION 39 | 32 sessions STANDARD_DEVIATION 63 | 31 sessions STANDARD_DEVIATION 52 |
| Opioid Use | 36 Participants | 40 Participants | 76 Participants |
| Oswestry Disability Index | 40 units on a scale STANDARD_DEVIATION 10 | 38 units on a scale STANDARD_DEVIATION 10 | 39 units on a scale STANDARD_DEVIATION 10 |
| Pain Duration (years from onset) | 14.4 years STANDARD_DEVIATION 10.8 | 13.9 years STANDARD_DEVIATION 10.4 | 14.2 years STANDARD_DEVIATION 10.6 |
| Percent of Days with Low Back Pain | 97 percent STANDARD_DEVIATION 8 | 97 percent STANDARD_DEVIATION 8 | 97 percent STANDARD_DEVIATION 8 |
| Previous Injection Procedures | 53 Participants | 46 Participants | 99 Participants |
| Previous Rhizotomy | 8 Participants | 17 Participants | 25 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 6 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 | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 96 Participants | 96 Participants | 192 Participants |
| Region of Enrollment Australia | 36 participants | 35 participants | 71 participants |
| Region of Enrollment Belgium | 9 participants | 8 participants | 17 participants |
| Region of Enrollment Netherlands | 2 participants | 4 participants | 6 participants |
| Region of Enrollment United Kingdom | 13 participants | 12 participants | 25 participants |
| Region of Enrollment United States | 42 participants | 43 participants | 85 participants |
| Sex: Female, Male Female | 56 Participants | 54 Participants | 110 Participants |
| Sex: Female, Male Male | 46 Participants | 48 Participants | 94 Participants |
| VAS for Low Back Pain | 7.3 units on a scale STANDARD_DEVIATION 0.7 | 7.2 units on a scale STANDARD_DEVIATION 0.7 | 7.3 units on a scale STANDARD_DEVIATION 0.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 102 | 0 / 102 | 0 / 99 | 0 / 99 |
| other Total, other adverse events | 32 / 102 | 24 / 102 | 25 / 99 | 34 / 99 |
| serious Total, serious adverse events | 4 / 102 | 6 / 102 | 3 / 99 | 2 / 99 |
Outcome results
Primary
Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels
The CPRA, which was prespecified in the clinical protocol and statistical analysis plan prior to the start of the trial, was performed using the same data as used for the primary endpoint analysis and was included as part of the primary endpoint analysis
Time frame: 120 Days
Population: 3 participants lost to follow-up included using multiple imputation.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >60% Reduction in Pain | 36.0 percentage of participants |
| Treatment | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >30% Reduction in Pain | 57.0 percentage of participants |
| Treatment | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >70% Reduction in Pain | 28.0 percentage of participants |
| Treatment | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >40% Reduction in Pain | 51.0 percentage of participants |
| Treatment | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >10% Reduction in Pain | 78.0 percentage of participants |
| Treatment | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >50% Reduction in Pain | 42.0 percentage of participants |
| Treatment | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >80% Reduction in Pain | 24.0 percentage of participants |
| Treatment | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >20% Reduction in Pain | 68.0 percentage of participants |
| Treatment | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >90% Reduction in Pain | 16.0 percentage of participants |
| Treatment | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >0% Reduction in Pain | 83.0 percentage of participants |
| Control | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >90% Reduction in Pain | 11.9 percentage of participants |
| Control | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >60% Reduction in Pain | 30.7 percentage of participants |
| Control | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >80% Reduction in Pain | 19.8 percentage of participants |
| Control | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >0% Reduction in Pain | 71.3 percentage of participants |
| Control | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >10% Reduction in Pain | 63.4 percentage of participants |
| Control | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >20% Reduction in Pain | 50.5 percentage of participants |
| Control | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >30% Reduction in Pain | 46.5 percentage of participants |
| Control | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >40% Reduction in Pain | 39.6 percentage of participants |
| Control | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >50% Reduction in Pain | 33.7 percentage of participants |
| Control | Cumulative Proportion of Responders Analysis (CPRA) for the Primary Endpoint to Compare Participants Responses Over a Full Range of Response Levels | >70% Reduction in Pain | 24.8 percentage of participants |
p-value: 0.0499Friedman's regression analysis
Primary
Mean Change in Low Back Pain VAS
Comparison of change in LBP VAS (120 days from baseline) between the Treatment and Control groups. The instrument used for evaluating pain is the continuous Visual Analog Scale (VAS) comprised of a horizontal line 10 cm in length, anchored by 2 verbal descriptors, where zero indicates no pain and 10 indicates worst imaginable pain. The value reported is a 7-day average low back pain. A change to a lower score (negative value) indicates improvement.
Time frame: 120 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Mean Change in Low Back Pain VAS | -3.3 score on a scale | Standard Deviation 2.7 |
| Control | Mean Change in Low Back Pain VAS | -2.4 score on a scale | Standard Deviation 2.9 |
p-value: 0.032t-test, 2 sided
Primary
Responder Rate of Low Back Pain With No Increase in Pain Medications
Comparison of responder rates for low back pain VAS between Treatment and Control groups. The Primary Efficacy Endpoint is a comparison of responder rates between Treatment and Control groups, where a responder is a participant with ≥30% reduction from baseline in average low back pain VAS, without any increase from baseline in pain medications and/or muscle relaxants for any reason including non low back pain reasons. The instrument used for evaluating pain is the continuous Visual Analog Scale (VAS) comprised of a horizontal line 10 cm in length, anchored by 2 verbal descriptors, where zero indicates no pain and 10 indicates worst imaginable pain. The value reported is a 7-day average low back pain. Any increase in dosage of a pain medication or any new pain medication taken for any reason counts as an increase in medications.
Time frame: 120 Days
Population: 100 treatment group participants and 101 control group participants returned for the 120 day visit. Results for the 3 participants lost to follow-up were included using multiple imputation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Responder Rate of Low Back Pain With No Increase in Pain Medications | 57.1 percentage of responsers |
| Control | Responder Rate of Low Back Pain With No Increase in Pain Medications | 46.6 percentage of responsers |
p-value: 0.138Wald asymptotic test of proportions
Primary
Serious Device and/or Procedure Related Adverse Event Rate
The primary safety assessment is of serious device and/or procedure related adverse events in all participants at 120 days. The 8 events reported below are 6 implant site pocket infections, 1 intra-operative upper airway obstruction, and 1 non-radicular, focal numbness on the surface of the thigh.
Time frame: 120 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Serious Device and/or Procedure Related Adverse Event Rate | 3 Participants |
| Control | Serious Device and/or Procedure Related Adverse Event Rate | 5 Participants |
Secondary
Change in European Quality of Life Score on Five Dimensions (EQ-5D)
Comparison of change in EQ-5D (120 days from baseline) between Treatment and Control groups. The EQ-5D Index is scored on a scale of -0.594 to 1.00, with a score of 1.00 indicating full health. A change to a higher score (positive value) indicates improvement.
Time frame: 120 Days
Population: Completers Analysis. Three participants (2 Treatment, 1 Control) were lost to follow-up. An additional patient in the Control group did not complete the questionnaire.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in European Quality of Life Score on Five Dimensions (EQ-5D) | 0.186 score on a scale | Standard Deviation 0.199 |
| Control | Change in European Quality of Life Score on Five Dimensions (EQ-5D) | 0.115 score on a scale | Standard Deviation 0.178 |
p-value: 0.009t-test, 2 sided
Secondary
Change in European Quality of Life Score on Five Dimensions (EQ-5D) at One Year
Change in EQ-5D at 1 year compared to baseline. The EQ-5D Index is scored on a scale of -0.594 to 1.00, with a score of 1.00 indicating full health. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy. A change to a higher score (positive value) indicates improvement.
Time frame: 1 Year
Population: Participants with data at one year.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in European Quality of Life Score on Five Dimensions (EQ-5D) at One Year | 0.210 score on a scale | Standard Deviation 0.235 |
| Control | Change in European Quality of Life Score on Five Dimensions (EQ-5D) at One Year | 0.187 score on a scale | Standard Deviation 0.177 |
| All (Treatment and Control/Crossover Combined) | Change in European Quality of Life Score on Five Dimensions (EQ-5D) at One Year | 0.198 score on a scale | Standard Deviation 0.207 |
Secondary
Change in Oswestry Disability Index (ODI)
Comparison of change in ODI (120 days from baseline) between Treatment and Control groups. ODI is reported as a score from 0 to 100%, where 0%-20% indicates minimal disability, 21%-40% indicates moderate disability, 41%-60% indicates severe disability, 61%-80% indicates crippled, and 81%-100% indicates bedbound or an exaggeration of symptoms. A change to a lower score (negative value) indicates improvement.
Time frame: 120 Days
Population: Completers Analysis. Three participants (2 Treatment, 1 Control) were lost to follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in Oswestry Disability Index (ODI) | -17.5 score on a scale | Standard Deviation 15.1 |
| Control | Change in Oswestry Disability Index (ODI) | -12.2 score on a scale | Standard Deviation 14.6 |
p-value: 0.011t-test, 2 sided
Secondary
Change in Oswestry Disability Index (ODI) at One Year
Change in ODI at 1 year compared to baseline. ODI is reported as a score from 0 to 100%, where 0%-20% indicates minimal disability, 21%-40% indicates moderate disability, 41%-60% indicates severe disability, 61%-80% indicates crippled, and 81%-100% indicates bedbound or an exaggeration of symptoms. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy. A change to a lower score (negative value) indicates improvement.
Time frame: 1 Year
Population: Participants with data at one year.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in Oswestry Disability Index (ODI) at One Year | -20.1 score on a scale | Standard Deviation 17.2 |
| Control | Change in Oswestry Disability Index (ODI) at One Year | -19.8 score on a scale | Standard Deviation 14.5 |
| All (Treatment and Control/Crossover Combined) | Change in Oswestry Disability Index (ODI) at One Year | -19.9 score on a scale | Standard Deviation 15.8 |
Secondary
Change in Percent Pain Relief (PPR)
PPR is a patient-reported percent of pain relief at 120 days compared to the pain at baseline, where 0% indicates no pain relief compared to baseline, and 100% indicates complete pain relief compared to baseline.
Time frame: 120 Days
Population: Completers Analysis. Three participants (2 Treatment, 1 Control) were lost to follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in Percent Pain Relief (PPR) | 52 score on a scale | Standard Deviation 32 |
| Control | Change in Percent Pain Relief (PPR) | 35 score on a scale | Standard Deviation 36 |
p-value: <0.001t-test, 2 sided
Secondary
LBP VAS Responder Rate at One Year
A responder is a participant with ≥30% reduction from baseline in average low back pain VAS, without any increase from baseline in pain medications and/or muscle relaxants for any reason including non low back pain reasons. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy.
Time frame: 1 Year
Population: Participants with data at one year.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | LBP VAS Responder Rate at One Year | 58 Participants |
| Control | LBP VAS Responder Rate at One Year | 57 Participants |
| All (Treatment and Control/Crossover Combined) | LBP VAS Responder Rate at One Year | 115 Participants |
Secondary
Mean Change in LBP VAS at One Year
Change in LBP VAS at 1 year compared to baseline. The instrument used for evaluating pain is the continuous Visual Analog Scale (VAS) comprised of a horizontal line 10 cm in length, anchored by 2 verbal descriptors, one for each symptom extreme for Low Back Pain. Zero indicates no pain and 10 indicates worst imaginable pain. The value reported is a 7-day average low back pain. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy. A change to a lower score (negative value) indicates improvement.
Time frame: 1 Year
Population: Participants with data at one year.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Mean Change in LBP VAS at One Year | -4.2 score on a scale | Standard Deviation 2.7 |
| Control | Mean Change in LBP VAS at One Year | -4.3 score on a scale | Standard Deviation 2.5 |
| All (Treatment and Control/Crossover Combined) | Mean Change in LBP VAS at One Year | -4.3 score on a scale | Standard Deviation 2.6 |
Secondary
Percent Pain Relief at One Year
PPR is a patient-reported percent of pain relief compared to the pain at baseline, where 0% indicates no pain relief compared to baseline, and 100% indicates complete pain relief compared to baseline. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy.
Time frame: 1 Year
Population: Participants with data at one year.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Percent Pain Relief at One Year | 65 score on a scale | Standard Deviation 33 |
| Control | Percent Pain Relief at One Year | 66 score on a scale | Standard Deviation 33 |
| All (Treatment and Control/Crossover Combined) | Percent Pain Relief at One Year | 66 score on a scale | Standard Deviation 32 |
Secondary
Resolution of Back Pain at One Year
Resolution of back pain (remitter rate) was defined as a participant with 7-day average low back pain VAS ≤2.5 cm on the 10 cm VAS. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy.
Time frame: 1 Year
Population: Participants with data at one year.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Resolution of Back Pain at One Year | 42 Participants |
| Control | Resolution of Back Pain at One Year | 49 Participants |
| All (Treatment and Control/Crossover Combined) | Resolution of Back Pain at One Year | 91 Participants |
Secondary
Resolution of Back Pain (VAS ≤2.5 cm)
Resolution of back pain (remitter rate) was defined as a participant with 7-day average low back pain VAS ≤2.5 cm on the 10 cm VAS.
Time frame: 120 Days
Population: Completers Analysis. Three participants (2 Treatment, 1 Control) were lost to follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Resolution of Back Pain (VAS ≤2.5 cm) | 34 Participants |
| Control | Resolution of Back Pain (VAS ≤2.5 cm) | 28 Participants |
p-value: 0.335Chi-squared
Secondary
Subject Global Impression of Change (SGIC)
A questionnaire completed with the following item: Since I enrolled in the study, my overall status is 1) Very much improved, 2) Much improved, 3) Minimally improved, 4) No change, 5) Minimally worse, 6) Much worse, 7) Very much worse
Time frame: 120 Days
Population: Completers Analysis. Three participants (2 Treatment, 1 Control) were lost to follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment | Subject Global Impression of Change (SGIC) | Better | 22 participants |
| Treatment | Subject Global Impression of Change (SGIC) | A Little Better | 25 participants |
| Treatment | Subject Global Impression of Change (SGIC) | Much Better | 32 participants |
| Treatment | Subject Global Impression of Change (SGIC) | No Change | 10 participants |
| Treatment | Subject Global Impression of Change (SGIC) | A Little Worse | 6 participants |
| Treatment | Subject Global Impression of Change (SGIC) | Worse | 4 participants |
| Treatment | Subject Global Impression of Change (SGIC) | Much Worse | 1 participants |
| Control | Subject Global Impression of Change (SGIC) | Much Worse | 3 participants |
| Control | Subject Global Impression of Change (SGIC) | Better | 16 participants |
| Control | Subject Global Impression of Change (SGIC) | Worse | 6 participants |
| Control | Subject Global Impression of Change (SGIC) | A Little Better | 29 participants |
| Control | Subject Global Impression of Change (SGIC) | No Change | 24 participants |
| Control | Subject Global Impression of Change (SGIC) | A Little Worse | 5 participants |
| Control | Subject Global Impression of Change (SGIC) | Much Better | 18 participants |
p-value: 0.003Wilcoxon (Mann-Whitney)
Secondary
Subject Global Impression of Change (SGIC) at One Year
A questionnaire with the following item: Since I enrolled in the study, my overall status is 1) Very much improved, 2) Much improved, 3) Minimally improved, 4) No change, 5) Minimally worse, 6) Much worse, 7) Very much worse After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy.
Time frame: 1 Year
Population: Participants with data at one year.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment | Subject Global Impression of Change (SGIC) at One Year | A Little Better | 14 Participants |
| Treatment | Subject Global Impression of Change (SGIC) at One Year | A Little Worse | 2 Participants |
| Treatment | Subject Global Impression of Change (SGIC) at One Year | No Change | 6 Participants |
| Treatment | Subject Global Impression of Change (SGIC) at One Year | Much Worse | 1 Participants |
| Treatment | Subject Global Impression of Change (SGIC) at One Year | Much Better | 44 Participants |
| Treatment | Subject Global Impression of Change (SGIC) at One Year | Worse | 1 Participants |
| Treatment | Subject Global Impression of Change (SGIC) at One Year | Better | 19 Participants |
| Control | Subject Global Impression of Change (SGIC) at One Year | Much Better | 40 Participants |
| Control | Subject Global Impression of Change (SGIC) at One Year | A Little Better | 14 Participants |
| Control | Subject Global Impression of Change (SGIC) at One Year | Better | 23 Participants |
| Control | Subject Global Impression of Change (SGIC) at One Year | No Change | 8 Participants |
| Control | Subject Global Impression of Change (SGIC) at One Year | A Little Worse | 2 Participants |
| Control | Subject Global Impression of Change (SGIC) at One Year | Worse | 1 Participants |
| Control | Subject Global Impression of Change (SGIC) at One Year | Much Worse | 1 Participants |
| All (Treatment and Control/Crossover Combined) | Subject Global Impression of Change (SGIC) at One Year | A Little Worse | 4 Participants |
| All (Treatment and Control/Crossover Combined) | Subject Global Impression of Change (SGIC) at One Year | Much Better | 84 Participants |
| All (Treatment and Control/Crossover Combined) | Subject Global Impression of Change (SGIC) at One Year | Much Worse | 2 Participants |
| All (Treatment and Control/Crossover Combined) | Subject Global Impression of Change (SGIC) at One Year | Worse | 2 Participants |
| All (Treatment and Control/Crossover Combined) | Subject Global Impression of Change (SGIC) at One Year | No Change | 14 Participants |
| All (Treatment and Control/Crossover Combined) | Subject Global Impression of Change (SGIC) at One Year | Better | 42 Participants |
| All (Treatment and Control/Crossover Combined) | Subject Global Impression of Change (SGIC) at One Year | A Little Better | 28 Participants |
Other Pre-specified
Change in Opioid Use for Treatment of Low Back Pain at One-Year
Any increase or decrease of dosage or frequency of an opioid taken for the treatment of low back pain was considered a change.
Time frame: 1 Year
Population: Participants with data at one year who were on opioids at baseline. Since changes in opioids are evaluated only at 1 year (and not compared between groups at 120 days), and all participants are receiving therapy at the 1 year time point, there is no between group comparison. Therefore, the groups are combined for this analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment | Change in Opioid Use for Treatment of Low Back Pain at One-Year | Discontinued or Decreased | 31 Participants |
| Treatment | Change in Opioid Use for Treatment of Low Back Pain at One-Year | No Change | 29 Participants |
| Treatment | Change in Opioid Use for Treatment of Low Back Pain at One-Year | Increased or Added | 5 Participants |
Other Pre-specified
Clinical Global Impression of Change
Clinical Global Impression consists of the following question completed by the Investigator prior to unblinding: In your opinion as a clinician, compared to the patient's situation at baseline, would you say the patient is: 1) Much better, 2) Slightly better, 3) About the same, 4) Slightly worse, 5) Much worse.
Time frame: 120 Days
Population: Completers Analysis. Three participants were lost to follow-up (2 Treatment, 1 Control). The questionnaire was not completed for an additional participant in the Control group.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment | Clinical Global Impression of Change | Slightly Worse | 1 Participants |
| Treatment | Clinical Global Impression of Change | Much Worse | 0 Participants |
| Treatment | Clinical Global Impression of Change | Slightly Better | 26 Participants |
| Treatment | Clinical Global Impression of Change | About the Same | 16 Participants |
| Treatment | Clinical Global Impression of Change | Much Better | 57 Participants |
| Control | Clinical Global Impression of Change | About the Same | 42 Participants |
| Control | Clinical Global Impression of Change | Slightly Worse | 5 Participants |
| Control | Clinical Global Impression of Change | Slightly Better | 29 Participants |
| Control | Clinical Global Impression of Change | Much Worse | 2 Participants |
| Control | Clinical Global Impression of Change | Much Better | 22 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
Other Pre-specified
Clinical Global Impression of Change at One Year
Clinical Global Impression consists of the following question completed by the Investigator prior to unblinding: In your opinion as a clinician, compared to the patient's situation at baseline, would you say the patient is: 1) Much better, 2) Slightly better, 3) About the same, 4) Slightly worse, 5) Much worse. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy.
Time frame: 1 Year
Population: Participants with data at one year.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment | Clinical Global Impression of Change at One Year | Much Better | 66 Participants |
| Treatment | Clinical Global Impression of Change at One Year | Much Worse | 1 Participants |
| Treatment | Clinical Global Impression of Change at One Year | Slightly Better | 11 Participants |
| Treatment | Clinical Global Impression of Change at One Year | About the Same | 8 Participants |
| Treatment | Clinical Global Impression of Change at One Year | Slightly Worse | 1 Participants |
| Control | Clinical Global Impression of Change at One Year | Much Worse | 0 Participants |
| Control | Clinical Global Impression of Change at One Year | Much Better | 63 Participants |
| Control | Clinical Global Impression of Change at One Year | About the Same | 10 Participants |
| Control | Clinical Global Impression of Change at One Year | Slightly Better | 15 Participants |
| Control | Clinical Global Impression of Change at One Year | Slightly Worse | 1 Participants |
| All (Treatment and Control/Crossover Combined) | Clinical Global Impression of Change at One Year | Much Worse | 1 Participants |
| All (Treatment and Control/Crossover Combined) | Clinical Global Impression of Change at One Year | About the Same | 18 Participants |
| All (Treatment and Control/Crossover Combined) | Clinical Global Impression of Change at One Year | Slightly Worse | 2 Participants |
| All (Treatment and Control/Crossover Combined) | Clinical Global Impression of Change at One Year | Much Better | 129 Participants |
| All (Treatment and Control/Crossover Combined) | Clinical Global Impression of Change at One Year | Slightly Better | 26 Participants |
Other Pre-specified
Supplementary Analysis of Primary Endpoint: Responder Rate of Low Back Pain With No Increase in Low Back Pain Medications
This pre-specified analysis of the primary endpoint examines the impact of rescue medications taken for acute pain conditions for reasons other than low back pain, by excluding those participants from the analysis who took rescue medications for reasons other than low back pain. Nine participants in both groups increased pain medications. In the control group, all nine participants increased pain medications due to low back pain. In the treatment group, three of the nine participants increased pain medications due to low back pain, while six of the nine participants increased pain medications for reasons other than low back pain. Since any increase in pain medications automatically considers a participant a non-responder, these six participants are removed from this analysis to eliminate the confounding factor of increases in pain medications for reasons other than low back pain.
Time frame: 120 Days
Population: Responder rate (≥30% reduction in low back pain VAS and no increase in pain medications). Six participants with increases in pain medications for reasons other than low back pain are removed from this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Supplementary Analysis of Primary Endpoint: Responder Rate of Low Back Pain With No Increase in Low Back Pain Medications | 60.6 percentage of responders |
| Control | Supplementary Analysis of Primary Endpoint: Responder Rate of Low Back Pain With No Increase in Low Back Pain Medications | 46.7 percentage of responders |
p-value: 0.048Wald asymptotic test of proportions
Other Pre-specified
Treatment Satisfaction
The Treatment Satisfaction Questionnaire asking the participant if they are satisfied with the treatment.
Time frame: 120 Days
Population: Completers Analysis. Three participants (2 Treatment, 1 Control) were lost to follow-up.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment | Treatment Satisfaction | Definitely Yes | 61 Participants |
| Treatment | Treatment Satisfaction | Maybe | 29 Participants |
| Treatment | Treatment Satisfaction | Definitely Not | 10 Participants |
| Control | Treatment Satisfaction | Definitely Yes | 40 Participants |
| Control | Treatment Satisfaction | Maybe | 37 Participants |
| Control | Treatment Satisfaction | Definitely Not | 24 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
Other Pre-specified
Treatment Satisfaction at One Year
The Treatment Satisfaction Questionnaire asking the participant if they are satisfied with the outcome of the treatment. After the 120 day visit, participants crossed over to have their device programmed to deliver stimulation at a patient-appropriate level. At the one-year time point, participants in the Control/Crossover group have received 8 months of patient-appropriate therapy.
Time frame: 1 Year
Population: Participants with data at one year.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment | Treatment Satisfaction at One Year | Maybe | 12 Participants |
| Treatment | Treatment Satisfaction at One Year | Definitely Yes | 68 Participants |
| Treatment | Treatment Satisfaction at One Year | Definitely Not | 6 Participants |
| Control | Treatment Satisfaction at One Year | Definitely Not | 3 Participants |
| Control | Treatment Satisfaction at One Year | Definitely Yes | 68 Participants |
| Control | Treatment Satisfaction at One Year | Maybe | 17 Participants |
| All (Treatment and Control/Crossover Combined) | Treatment Satisfaction at One Year | Definitely Not | 9 Participants |
| All (Treatment and Control/Crossover Combined) | Treatment Satisfaction at One Year | Definitely Yes | 136 Participants |
| All (Treatment and Control/Crossover Combined) | Treatment Satisfaction at One Year | Maybe | 29 Participants |