Painful Diabetic Neuropathy
Conditions
Brief summary
This post-market study is being conducted to document comparative safety, clinical effectiveness, and cost-effectiveness of the addition of HF10™ therapy to CMM compared with CMM alone in subjects with chronic, intractable, neuropathic lower limb pain due to diabetic neuropathy (Painful Diabetic Neuropathy or PDN). This study is a multi-center, prospective, randomized comparison of the two treatments.
Interventions
DEVICESenza HF10 Therapy
Senza 10kHz Spinal Cord Stimulation
OTHERCMM
Conventional Medical Management
Sponsors
Nevro Corp
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
22 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Have been clinically diagnosed with painful diabetic neuropathy (PDN) of the lower limbs. 2. Average pain intensity of ≥ 5 out of 10 cm on the VAS in the lower extremities at enrollment. 3. Have stable neurological status. 4. Be on a stable analgesic regimen. 5. Be 22 years of age or older at the time of enrollment. 6. Be an appropriate candidate for the surgical procedures required in this study. 7. Be capable of subjective evaluation, able to read and understand English-written questionnaires, and able to read, understand and sign the written informed consent in English. 8. Be willing and capable of giving informed consent. 9. Be willing and able to comply with study-related requirements, procedures, and scheduled visits.
Exclusion criteria
1. Have a diagnosis of a lower limb mononeuropathy, have had a lower limb amputation, or have large (≥3 cm) and/or gangrenous ulcers of the lower limbs. 2. Have a BMI ≥ 40. 3. Currently prescribed a daily opioid dosage \> 120 mg morphine equivalents. 4. Have a medical condition or pain in other area(s), not intended to be treated in this study. 5. Have a current diagnosis of a progressive neurological disease such a multiple sclerosis, chronic inflammatory demyelinating polyneuropathy, rapidly progressive arachnoiditis, brain or spinal cord tumor, central deafferentation syndrome, Complex Regional Pain Syndrome, acute herniating disc, severe spinal stenosis and brachial plexus injury. 6. Have a current diagnosis or condition such as a coagulation disorder, bleeding diathesis, platelet dysfunction, low platelet count, severely diminished functional capacity due to underlying cardiac/pulmonary disease, symptomatic uncontrolled hypertension, progressive peripheral vascular disease or uncontrolled diabetes mellitus that presents excess risk for performing the procedure. 7. Have failed prior SCS, dorsal root ganglion (DRG) stimulation, or peripheral nerve stimulation (PNS) trials for chronic intractable pain. 8. Have significant spinal stenosis, objective evidence of epidural scarring and/or any signs or symptoms of myelopathy. 9. Any previous history of surgery on the posterior elements (laminectomy, posterior fusion) resulting in a compromised epidural space. 10. Be benefitting from an interventional procedure and/or surgery to treat lower limb pain. 11. Have an existing drug pump and/or another active implantable device such as a pacemaker. 12. Have a condition currently requiring or likely to require the use of diathermy or MRI that is inconsistent with Senza system guidelines in the Physician's Manual. 13. Have either a metastatic malignant neoplasm or untreated local malignant neoplasm. 14. Have a life expectancy of less than one year. 15. Have a local infection at the anticipated surgical entry site or an active systemic infection. 16. Be pregnant or plan to become pregnant during the study. Women of childbearing potential who are sexually active must use a reliable form of birth control, be surgically sterile, or be at least 2 years post-menopausal. 17. Have within 6 months of enrollment a significant untreated addiction to dependency producing medications, alcohol or illicit drugs. 18. Be concomitantly participating in another clinical study. 19. Be involved in an injury claim under current litigation. 20. Be a recipient of Social Security Disability Insurance (SSDI). 21. Have a pending or approved worker's compensation claim. 22. Have evidence of an active disruptive psychological or psychiatric disorder or other known condition significant enough to impact perception of pain, compliance with intervention and/or ability to evaluate treatment outcome.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of Safety and Effectiveness | 3 months | Difference between treatment groups in responder rates in subjects without a clinically meaningful neurological deficit compared with baseline. Responder is defined as a subject who has at least 50% reduction in lower limb pain from Baseline as measured by a 10 cm Visual Analog Scale (VAS). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Scores of 3 or Less | 3 months | Difference between the treatment groups in proportion of subjects with a lower limb pain VAS score ≤ 3 cm. |
| Crossover Rates | 6 months | Difference between the treatment groups in crossover rates. Subjects who meet pre-specified criteria may elect to crossover to the other treatment arm at 6-month follow-up. |
| Responder Rates | 6 months | Difference between the treatment groups in responder rates. Responder is defined as a subject who has at least 50% reduction in lower limb pain from Baseline as measured by a 10 cm Visual Analog Scale (VAS). |
| Remitter Rates | 6 months | Difference between the treatment groups in the proportion of remitters (remission is defined as having a lower limb pain VAS score of ≤ 3.0 cm for at least 6 months). |
| Neurological Assessment | 3 months | Difference between the treatment groups in the proportion of subjects with overall improvement from baseline in neurological assessment (motor, sensory, reflex). |
| Health-related Quality of Life | 6 months | Difference between the treatment groups in changes in health-related quality of life as assessed by the EuroQol Five Dimensions questionnaire (EQ-5D-5L). |
| Hemoglobin A1c | 6 months | Difference between the treatment groups in the average percentage change from baseline in HbA1c levels. |
Countries
United States
Contacts
STUDY_DIRECTORDavid Caraway, MD
Nevro Corp
Participant flow
Pre-assignment details
Participants underwent screening prior to randomization to verify satisfaction of all inclusion/exclusion criteria. Medical records for enrolled participants were evaluated by independent medical monitors for oversight of appropriate patient selection.
Participants by arm
| Arm | Count |
|---|---|
| HF10 Therapy Plus CMM The addition of HF10 (10kHz SCS) therapy to Conventional Medical Management
Senza HF10 Therapy: Senza 10kHz Spinal Cord Stimulation | 113 |
| CMM Alone Conventional Medical Management
CMM: Conventional Medical Management | 103 |
| Total | 216 |
Baseline characteristics
| Characteristic | HF10 Therapy Plus CMM | CMM Alone | Total |
|---|---|---|---|
| Age, Continuous | 60.7 years STANDARD_DEVIATION 11.4 | 60.8 years STANDARD_DEVIATION 9.9 | 60.8 years STANDARD_DEVIATION 10.7 |
| Lower limb pain visual analog scale (VAS) score | 7.5 cm STANDARD_DEVIATION 1.6 | 7.1 cm STANDARD_DEVIATION 1.6 | 7.3 cm STANDARD_DEVIATION 1.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants | 13 Participants | 31 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 87 Participants | 85 Participants | 172 Participants |
| Sex: Female, Male Female | 43 Participants | 37 Participants | 80 Participants |
| Sex: Female, Male Male | 70 Participants | 66 Participants | 136 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 113 | 0 / 103 |
| other Total, other adverse events | 0 / 113 | 0 / 103 |
| serious Total, serious adverse events | 12 / 113 | 9 / 103 |
Outcome results
Primary
Composite of Safety and Effectiveness
Difference between treatment groups in responder rates in subjects without a clinically meaningful neurological deficit compared with baseline. Responder is defined as a subject who has at least 50% reduction in lower limb pain from Baseline as measured by a 10 cm Visual Analog Scale (VAS).
Time frame: 3 months
Population: Intention-to-treat population including all randomized patients whose status could be determined at the 3-month primary assessment, including patients who failed trial SCS and those who withdrew due to an adverse event at any point after the trial SCS phase in the active treatment arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HF10 Therapy Plus CMM | Composite of Safety and Effectiveness | 75 Participants |
| CMM Alone | Composite of Safety and Effectiveness | 5 Participants |
p-value: <0.001Fisher Exact
Secondary
Crossover Rates
Difference between the treatment groups in crossover rates. Subjects who meet pre-specified criteria may elect to crossover to the other treatment arm at 6-month follow-up.
Time frame: 6 months
Secondary
Health-related Quality of Life
Difference between the treatment groups in changes in health-related quality of life as assessed by the EuroQol Five Dimensions questionnaire (EQ-5D-5L).
Time frame: 6 months
Secondary
Hemoglobin A1c
Difference between the treatment groups in the average percentage change from baseline in HbA1c levels.
Time frame: 6 months
Secondary
Neurological Assessment
Difference between the treatment groups in the proportion of subjects with overall improvement from baseline in neurological assessment (motor, sensory, reflex).
Time frame: 3 months
Secondary
Neurological Assessment
Difference between the treatment groups in the proportion of subjects with overall improvement from baseline in neurological assessment (motor, sensory, reflex).
Time frame: 6 months
Secondary
Pain Scores of 3 or Less
Difference between the treatment groups in proportion of subjects with a lower limb pain VAS score ≤ 3 cm.
Time frame: 3 months
Secondary
Remitter Rates
Difference between the treatment groups in the proportion of remitters (remission is defined as having a lower limb pain VAS score of ≤ 3.0 cm for at least 6 months).
Time frame: 6 months
Secondary
Responder Rates
Difference between the treatment groups in responder rates. Responder is defined as a subject who has at least 50% reduction in lower limb pain from Baseline as measured by a 10 cm Visual Analog Scale (VAS).
Time frame: 6 months