Chronic Leg Pain, Chronic Low Back Pain
Conditions
Brief summary
A BIOTRONIK wearable stimulator will be utilized in order to investigate the effects of two study spinal cord stimulation (SCS) therapies on subject reported pain and paresthesia perception observed over 12 days of study stimulation testing following the conclusion of a successful SCS commercial trial.
Detailed description
The study population will consist of patients with chronic low back and/or leg pain who have been identified as candidates for trial testing of a commercially available SCS system including percutaneous SCS trial lead(s), but have not yet undergone trial lead implant. The commercial trial test period will be conducted independently from the study according to standard of care. The commercial trial period is referred to as the trial and the BENEFIT-02 interventional study stimulation period is referred to as the study. Potential subjects will be identified by the investigator from their general patient population and must meet all of the study inclusion and none of the study exclusion criteria evaluated at the time of enrollment. Once study eligibility is confirmed, written informed consent is obtained, after which enrollment visit data will be collected. Subjects will be considered fully enrolled after being randomly assigned to receive one of two study SCS therapies. To participate in this study, subjects must be willing to undergo an extended 14 day testing period following the conclusion of their commercial trial, where their existing SCS trial lead(s) will be connected to a BIOTRONIK study stimulator and one of two randomly assigned study SCS therapies will be administered for an additional 12 days after a two day washout period. After completion of the 12 day study testing period, the subject's participation in the study ends, the study stimulator will be disconnected, and the commercial SCS trial lead(s) will be removed according to the standard clinical routine. This feasibility study includes the assessment of two primary endpoints and two secondary endpoints that are designed to provide preliminary information regarding the effectiveness and safety of the two study SCS therapies under investigation in the study.
Interventions
DEVICETherapy A spinal cord stimulation parameter set using BIO-RNA system and associated components
Therapy A stimulation patterns
DEVICETherapy B spinal cord stimulation parameter set using BIO-RNA system and associated components
Therapy B stimulation patterns
Sponsors
Biotronik, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age greater than or equal to 18 years * Able to understand the nature of the study and provide written informed consent * Able to read, understand, and speak English * Willing and able to comply with all study requirements, including all required procedures, phone calls and study visits * Planned to undergo a commercial SCS trial of standard duration for the treatment of low back and/or leg pain with a commercially available SCS system as prescribed by a physician(s) according to FDA approved indications for use * Planned utilization of preoperative antibiotics for SCS commercial trial * Planned placement of two eight-electrode SCS trial leads (or at least one 16- electrode SCS trial lead) using a suitable technique for an extended trial (e.g. tunneling approach of a minimum of 3-4 cm, or buried lead trial) with at least one lead covering the T8 or T9 vertebral level * Incoming Numerical Rating Scale (NRS) for pain (overall) of at least 6 (collected prior to the commercial trial) * Passed psychological evaluation * Negative MRSA screening result * Negative MSSA screening result or documentation of subsequent decolonization routine if MSSA positive * For diabetic patients: minimum of one HbA1c test within the last 6 months, with most recent result ≤ 7.5%
Exclusion criteria
* Enrolled in any investigational SCS stimulation trial, for which the SCS system is not commercially available * Presence of any life-threatening, underlying illness separate from their indication for SCS therapy * Patients reporting pregnancy at the time of enrollment * Patients with poor compliance for pain management regimen * Patients currently involved in an active workers compensation claim and/or active litigation related to injury associated with indication for SCS * Patients with a documented history of substance abuse (narcotics, alcohol, etc.) or substance dependency (other than prescribed) in the 6 months prior to baseline data collection * Patients with an implanted pacemaker, defibrillator, or other medical contraindications for SCS therapy * Patients with a medical condition or pain in other area(s), not intended to be treated with SCS, that could interfere with study procedures, accurate pain reporting, and/or confound evaluation of study endpoints, as determined by the investigator * Patients immunocompromised and/or at high risk for infection * Patients with morphine equivalent dose \> 120 units * Patients with documented history of allergic response or sensitivity to material(s) required for the study (e.g. silver impregnated antibacterial dressing, adhesives, titanium, silicone, etc.) * Patients with a documented history of clostridium difficile
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change Since Baseline in Numerical Rating Scale (NRS) for Pain (Overall) Evaluated Separately for Each Study SCS Therapy | Baseline and in-office visit 3, average of 21 days | The purpose of primary endpoint 1 is to evaluate the change since baseline in Numerical Rating Scale (NRS) for pain (overall) for each study SCS therapy. The evaluation of primary endpoint 1 is based on the NRS for pain (overall) obtained at the final study testing visit compared with the baseline measurement obtained prior to initiation of the commercial trial period, for subjects randomized to each study SCS therapy. Numerical Rating Scale (NRS) was collected for overall pain experienced over the past 24 hours on a scale of 0-10, with 0 being No Pain and 10 being Worst Possible Pain. |
| Inter-therapy Comparison of Change Since Baseline in Numerical Rating Scale (NRS) for Pain (Overall) | Baseline and in-office visit 3, average of 21 days | The purpose of primary endpoint 2 is to provide an inter-therapy comparison of change since baseline in Numerical Rating Scale (NRS) for pain (overall). Primary endpoint 2 analyses includes all participants included in primary endpoint 1 analyses. Numerical Rating Scale (NRS) was collected for overall pain experienced over the past 24 hours on a scale of 0-10, with 0 being No Pain and 10 being Worst Possible Pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change Since Conclusion of Commercial Trial in Numerical Rating Scale (NRS) for Pain (Overall) Evaluated Separately for Each Study SCS Therapy | In-office visit 1 at approximately 7 days and in-office visit 3 at approximately 21 days, average of 14 days | The evaluation of secondary endpoint 1 will be based on Numerical Rating Scale (NRS) for overall pain experienced over the past 24 hours (scale of 0-10, with 0 being No Pain and 10 being Worst Possible Pain) obtained at conclusion of commercial trial compared to NRS for overall pain at the final study testing visit |
| Investigational Device-related Adverse Event-free Rate | Baseline and in-office visit 3, average of 21 days | The evaluation of secondary endpoint 2 will be based on the number of subjects free from investigational device-related adverse events assessed at in-office visit 1 (randomization visit) through in-office visit 3 (study completion). The investigational device-related adverse event-free rate was pre-defined within the protocol as the overall rate from all implanted Prospera SCS devices, regardless of randomized therapy output setting (Therapy A or Therapy B). |
Countries
United States
Participant flow
Pre-assignment details
Of 136 provisionally enrolled participants, 77 met the criteria to be randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Enrolled But Not Randomized Subjects selected for participation from the investigator's patient population who have signed the Informed Consent Form, have confirmation of the initial enrollment criteria, and have completed baseline measurements, but did not meet criteria to be randomized at office visit 1. | 59 |
| Therapy A Subjects meeting all eligibility criteria at office visit 1 and are subsequently randomized to Therapy A (\
600-1500Hz) spinal cord stimulation parameter set. | 38 |
| Therapy B Subjects meeting all eligibility criteria at office visit 1 and are subsequently randomized to Therapy B (\
300-600Hz) spinal cord stimulation parameter set. | 39 |
| Total | 136 |
Baseline characteristics
| Characteristic | Therapy A | Enrolled But Not Randomized | Therapy B | Total |
|---|---|---|---|---|
| Age, Continuous | 60.8 Years STANDARD_DEVIATION 13.25 | 63.9 Years STANDARD_DEVIATION 12.09 | 60.4 Years STANDARD_DEVIATION 13.79 | 62 Years STANDARD_DEVIATION 12.93 |
| Clinical Characteristics - Previous Back Surgery No | 13 Participants | 27 Participants | 14 Participants | 54 Participants |
| Clinical Characteristics - Previous Back Surgery Unknown | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Clinical Characteristics - Previous Back Surgery Yes | 25 Participants | 31 Participants | 25 Participants | 81 Participants |
| Clinical Characteristics - Primary Pain Diagnosis Chronic pain syndrome | 3 Participants | 5 Participants | 6 Participants | 14 Participants |
| Clinical Characteristics - Primary Pain Diagnosis Complex regional pain syndrome | 4 Participants | 8 Participants | 4 Participants | 16 Participants |
| Clinical Characteristics - Primary Pain Diagnosis Degenerative disc disease | 3 Participants | 5 Participants | 3 Participants | 11 Participants |
| Clinical Characteristics - Primary Pain Diagnosis Dorsalgia | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Clinical Characteristics - Primary Pain Diagnosis Failed back surgery syndrome | 13 Participants | 16 Participants | 11 Participants | 40 Participants |
| Clinical Characteristics - Primary Pain Diagnosis Low back pain | 1 Participants | 3 Participants | 4 Participants | 8 Participants |
| Clinical Characteristics - Primary Pain Diagnosis Other primary pain diagnosis | 2 Participants | 3 Participants | 0 Participants | 5 Participants |
| Clinical Characteristics - Primary Pain Diagnosis Radiculopathy | 8 Participants | 9 Participants | 7 Participants | 24 Participants |
| Clinical Characteristics - Primary Pain Diagnosis Spinal stenosis | 2 Participants | 4 Participants | 3 Participants | 9 Participants |
| Clinical Characteristics - Primary Pain Diagnosis Spondylosis | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Clinical Characteristics - Primary Pain Diagnosis Unknown primary pain diagnosis | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Clinical Characteristics - Taking Opioid Analgesics No | 19 Participants | 22 Participants | 18 Participants | 59 Participants |
| Clinical Characteristics - Taking Opioid Analgesics Unknown | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Clinical Characteristics - Taking Opioid Analgesics Yes | 19 Participants | 34 Participants | 21 Participants | 74 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants | 49 Participants | 33 Participants | 114 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 7 Participants | 5 Participants | 17 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 7 Participants | 4 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 1 Participants | 9 Participants |
| Race (NIH/OMB) White | 31 Participants | 45 Participants | 33 Participants | 109 Participants |
| Sex: Female, Male Female | 25 Participants | 33 Participants | 24 Participants | 82 Participants |
| Sex: Female, Male Male | 13 Participants | 26 Participants | 15 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 59 | 0 / 38 | 0 / 39 |
| other Total, other adverse events | 2 / 59 | 3 / 38 | 3 / 39 |
| serious Total, serious adverse events | 0 / 59 | 0 / 38 | 0 / 39 |
Outcome results
Primary
Change Since Baseline in Numerical Rating Scale (NRS) for Pain (Overall) Evaluated Separately for Each Study SCS Therapy
The purpose of primary endpoint 1 is to evaluate the change since baseline in Numerical Rating Scale (NRS) for pain (overall) for each study SCS therapy. The evaluation of primary endpoint 1 is based on the NRS for pain (overall) obtained at the final study testing visit compared with the baseline measurement obtained prior to initiation of the commercial trial period, for subjects randomized to each study SCS therapy. Numerical Rating Scale (NRS) was collected for overall pain experienced over the past 24 hours on a scale of 0-10, with 0 being No Pain and 10 being Worst Possible Pain.
Time frame: Baseline and in-office visit 3, average of 21 days
Population: Only patients with valid NRS for pain (overall) at both baseline and at in-office visit 3 were evaluated for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Therapy A Spinal Cord Stimulation Parameter Set | Change Since Baseline in Numerical Rating Scale (NRS) for Pain (Overall) Evaluated Separately for Each Study SCS Therapy | -4.3 Score on a scale | Standard Deviation 0.47 |
| Therapy B Spinal Cord Stimulation Parameter Set | Change Since Baseline in Numerical Rating Scale (NRS) for Pain (Overall) Evaluated Separately for Each Study SCS Therapy | -4.7 Score on a scale | Standard Deviation 0.48 |
p-value: <0.0001paired t-test, two-sided
p-value: <0.0001paired t-test, two-sided
Primary
Inter-therapy Comparison of Change Since Baseline in Numerical Rating Scale (NRS) for Pain (Overall)
The purpose of primary endpoint 2 is to provide an inter-therapy comparison of change since baseline in Numerical Rating Scale (NRS) for pain (overall). Primary endpoint 2 analyses includes all participants included in primary endpoint 1 analyses. Numerical Rating Scale (NRS) was collected for overall pain experienced over the past 24 hours on a scale of 0-10, with 0 being No Pain and 10 being Worst Possible Pain.
Time frame: Baseline and in-office visit 3, average of 21 days
Population: Only patients with valid NRS for pain (overall) at both baseline and at in-office visit 3 were evaluated for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Therapy A Spinal Cord Stimulation Parameter Set | Inter-therapy Comparison of Change Since Baseline in Numerical Rating Scale (NRS) for Pain (Overall) | -4.3 Score on a scale | Standard Deviation 0.47 |
| Therapy B Spinal Cord Stimulation Parameter Set | Inter-therapy Comparison of Change Since Baseline in Numerical Rating Scale (NRS) for Pain (Overall) | -4.7 Score on a scale | Standard Deviation 0.48 |
p-value: 0.5482two-sample t-test, 2-sided
Secondary
Change Since Conclusion of Commercial Trial in Numerical Rating Scale (NRS) for Pain (Overall) Evaluated Separately for Each Study SCS Therapy
The evaluation of secondary endpoint 1 will be based on Numerical Rating Scale (NRS) for overall pain experienced over the past 24 hours (scale of 0-10, with 0 being No Pain and 10 being Worst Possible Pain) obtained at conclusion of commercial trial compared to NRS for overall pain at the final study testing visit
Time frame: In-office visit 1 at approximately 7 days and in-office visit 3 at approximately 21 days, average of 14 days
Population: Only patients with valid NRS for pain (overall) at both in-office visit 1 and in-office visit 3 were evaluated for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Therapy A Spinal Cord Stimulation Parameter Set | Change Since Conclusion of Commercial Trial in Numerical Rating Scale (NRS) for Pain (Overall) Evaluated Separately for Each Study SCS Therapy | 1.0 Score on a scale | Standard Deviation 0.53 |
| Therapy B Spinal Cord Stimulation Parameter Set | Change Since Conclusion of Commercial Trial in Numerical Rating Scale (NRS) for Pain (Overall) Evaluated Separately for Each Study SCS Therapy | 0.3 Score on a scale | Standard Deviation 0.32 |
Secondary
Investigational Device-related Adverse Event-free Rate
The evaluation of secondary endpoint 2 will be based on the number of subjects free from investigational device-related adverse events assessed at in-office visit 1 (randomization visit) through in-office visit 3 (study completion). The investigational device-related adverse event-free rate was pre-defined within the protocol as the overall rate from all implanted Prospera SCS devices, regardless of randomized therapy output setting (Therapy A or Therapy B).
Time frame: Baseline and in-office visit 3, average of 21 days
Population: Evaluable subjects for secondary endpoint 2 will include all subjects who undergo randomization and have the investigational stimulation system connected to their SCS trial leads. The investigational device-related adverse event-free rate was pre-defined within the protocol as the overall rate from all implanted Prospera SCS devices, regardless of randomized therapy output setting (Therapy A or Therapy B). Therefore, data for Therapy A and Therapy B are combined for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Therapy A Spinal Cord Stimulation Parameter Set | Investigational Device-related Adverse Event-free Rate | 76 Participants |