SENZA-PDN: Comparison of 10 kHz SCS Combined With CMM to CMM Alone in the Treatment of Neuropathic Limb Pain
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: HF10 therapy plus CMM The addition of HF10 (10kHz SCS) therapy to Conventional Medical Management |
Device: Senza HF10 Therapy
Senza 10kHz Spinal Cord Stimulation
|
| Other: CMM Alone Conventional Medical Management |
Other: CMM
Conventional Medical Management
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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).
- Neurological Assessment [6 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Have been clinically diagnosed with painful diabetic neuropathy (PDN) of the lower limbs.
-
Average pain intensity of ≥ 5 out of 10 cm on the VAS in the lower extremities at enrollment.
-
Have stable neurological status.
-
Be on a stable analgesic regimen.
-
Be 22 years of age or older at the time of enrollment.
-
Be an appropriate candidate for the surgical procedures required in this study.
-
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.
-
Be willing and capable of giving informed consent.
-
Be willing and able to comply with study-related requirements, procedures, and scheduled visits.
Exclusion Criteria:
-
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.
-
Have a BMI ≥ 40.
-
Currently prescribed a daily opioid dosage > 120 mg morphine equivalents.
-
Have a medical condition or pain in other area(s), not intended to be treated in this study.
-
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.
-
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.
-
Have failed prior SCS, dorsal root ganglion (DRG) stimulation, or peripheral nerve stimulation (PNS) trials for chronic intractable pain.
-
Have significant spinal stenosis, objective evidence of epidural scarring and/or any signs or symptoms of myelopathy.
-
Any previous history of surgery on the posterior elements (laminectomy, posterior fusion) resulting in a compromised epidural space.
-
Be benefitting from an interventional procedure and/or surgery to treat lower limb pain.
-
Have an existing drug pump and/or another active implantable device such as a pacemaker.
-
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.
-
Have either a metastatic malignant neoplasm or untreated local malignant neoplasm.
-
Have a life expectancy of less than one year.
-
Have a local infection at the anticipated surgical entry site or an active systemic infection.
-
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.
-
Have within 6 months of enrollment a significant untreated addiction to dependency producing medications, alcohol or illicit drugs.
-
Be concomitantly participating in another clinical study.
-
Be involved in an injury claim under current litigation.
-
Be a recipient of Social Security Disability Insurance (SSDI).
-
Have a pending or approved worker's compensation claim.
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Coastal Orthopedics | Bradenton | Florida | United States | 34209 |
| 2 | Georgia Pain Care | Stockbridge | Georgia | United States | 30281 |
| 3 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 4 | Advanced Pain Management | Greenfield | Wisconsin | United States | 53221 |
Sponsors and Collaborators
- Nevro Corp
Investigators
- Study Director: David Caraway, MD, Nevro Corp
Study Documents (Full-Text)
More Information
Publications
None provided.- CA2016-5
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | HF10 Therapy Plus CMM | CMM Alone |
|---|---|---|
| Arm/Group Description | The addition of HF10 (10kHz SCS) therapy to Conventional Medical Management Senza HF10 Therapy: Senza 10kHz Spinal Cord Stimulation | Conventional Medical Management CMM: Conventional Medical Management |
| Period Title: Overall Study | ||
| STARTED | 113 | 103 |
| Month-1 | 95 | 101 |
| Month-3 | 93 | 98 |
| COMPLETED | 93 | 98 |
| NOT COMPLETED | 20 | 5 |
Baseline Characteristics
| Arm/Group Title | HF10 Therapy Plus CMM | CMM Alone | Total |
|---|---|---|---|
| Arm/Group Description | The addition of HF10 (10kHz SCS) therapy to Conventional Medical Management Senza HF10 Therapy: Senza 10kHz Spinal Cord Stimulation | Conventional Medical Management CMM: Conventional Medical Management | Total of all reporting groups |
| Overall Participants | 113 | 103 | 216 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
60.7
(11.4)
|
60.8
(9.9)
|
60.8
(10.7)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
43
38.1%
|
37
35.9%
|
80
37%
|
| Male |
70
61.9%
|
66
64.1%
|
136
63%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
2
1.8%
|
0
0%
|
2
0.9%
|
| Asian |
1
0.9%
|
1
1%
|
2
0.9%
|
| Native Hawaiian or Other Pacific Islander |
3
2.7%
|
1
1%
|
4
1.9%
|
| Black or African American |
18
15.9%
|
13
12.6%
|
31
14.4%
|
| White |
87
77%
|
85
82.5%
|
172
79.6%
|
| More than one race |
2
1.8%
|
3
2.9%
|
5
2.3%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Lower limb pain visual analog scale (VAS) score (cm) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [cm] |
7.5
(1.6)
|
7.1
(1.6)
|
7.3
(1.6)
|
Outcome Measures
| Title | Composite of Safety and Effectiveness |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | HF10 Therapy Plus CMM | CMM Alone |
|---|---|---|
| Arm/Group Description | The addition of HF10 (10kHz SCS) therapy to Conventional Medical Management Senza HF10 Therapy: Senza 10kHz Spinal Cord Stimulation | Conventional Medical Management CMM: Conventional Medical Management |
| Measure Participants | 95 | 94 |
| Count of Participants [Participants] |
75
66.4%
|
5
4.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | HF10 Therapy Plus CMM, CMM Alone |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | 2-sided alpha level of 0.05 | |
| Method | Fisher Exact | |
| Comments | ||
| Title | Pain Scores of 3 or Less |
|---|---|
| Description | Difference between the treatment groups in proportion of subjects with a lower limb pain VAS score ≤ 3 cm. |
| Time Frame | 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Crossover Rates |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Responder Rates |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Remitter Rates |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Neurological Assessment |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Neurological Assessment |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Health-related Quality of Life |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Hemoglobin A1c |
|---|---|
| Description | Difference between the treatment groups in the average percentage change from baseline in HbA1c levels. |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | 3 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | HF10 Therapy Plus CMM | CMM Alone | ||
| Arm/Group Description | The addition of HF10 (10kHz SCS) therapy to Conventional Medical Management Senza HF10 Therapy: Senza 10kHz Spinal Cord Stimulation | Conventional Medical Management CMM: Conventional Medical Management | ||
All Cause Mortality |
||||
| HF10 Therapy Plus CMM | CMM Alone | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/113 (0.9%) | 0/103 (0%) | ||
Serious Adverse Events |
||||
| HF10 Therapy Plus CMM | CMM Alone | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 12/113 (10.6%) | 9/103 (8.7%) | ||
| Cardiac disorders | ||||
| Acute myocardial infarction | 1/113 (0.9%) | 1 | 1/103 (1%) | 1 |
| Coronary artery disease | 1/113 (0.9%) | 1 | 0/103 (0%) | 0 |
| Cardiac arrest | 1/113 (0.9%) | 1 | 0/103 (0%) | 0 |
| Myocardial infarction | 0/113 (0%) | 0 | 1/103 (1%) | 1 |
| Gastrointestinal disorders | ||||
| Diarrhoea | 0/113 (0%) | 0 | 1/103 (1%) | 1 |
| Nausea | 0/113 (0%) | 0 | 1/103 (1%) | 1 |
| Pancreatic mass | 1/113 (0.9%) | 1 | 0/103 (0%) | 0 |
| Pancreatitis chronic | 1/113 (0.9%) | 1 | 0/103 (0%) | 0 |
| Pancreatic disorder | 0/113 (0%) | 0 | 1/103 (1%) | 1 |
| General disorders | ||||
| Chest pain | 1/113 (0.9%) | 1 | 0/103 (0%) | 0 |
| Pyrexia | 1/113 (0.9%) | 1 | 0/103 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Cholangitis acute | 1/113 (0.9%) | 1 | 0/103 (0%) | 0 |
| Infections and infestations | ||||
| Sepsis | 1/113 (0.9%) | 1 | 1/103 (1%) | 1 |
| Localised infection | 1/113 (0.9%) | 1 | 0/103 (0%) | 0 |
| Wound infection staphylococcal | 0/113 (0%) | 0 | 1/103 (1%) | 1 |
| Pneumonia | 1/113 (0.9%) | 1 | 1/103 (1%) | 1 |
| Septic shock | 0/113 (0%) | 0 | 1/103 (1%) | 1 |
| Staphylococcal infection | 0/113 (0%) | 0 | 1/103 (1%) | 1 |
| Wound infection | 1/113 (0.9%) | 1 | 0/103 (0%) | 0 |
| Endocarditis | 0/113 (0%) | 0 | 1/103 (1%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Extradural haematoma | 1/113 (0.9%) | 1 | 0/103 (0%) | 0 |
| Cervical vertebral fracture | 0/113 (0%) | 0 | 1/103 (1%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Osteoarthritis | 1/113 (0.9%) | 1 | 0/103 (0%) | 0 |
| Nervous system disorders | ||||
| Paraplegia | 1/113 (0.9%) | 1 | 0/103 (0%) | 0 |
| Headache | 0/113 (0%) | 0 | 1/103 (1%) | 1 |
| Embolic stroke | 0/113 (0%) | 0 | 1/103 (1%) | 1 |
| Encephalopathy | 0/113 (0%) | 0 | 1/103 (1%) | 1 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 0/113 (0%) | 0 | 1/103 (1%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute respiratory failure | 1/113 (0.9%) | 1 | 0/103 (0%) | 0 |
| Vascular disorders | ||||
| Hypotension | 1/113 (0.9%) | 1 | 0/103 (0%) | 0 |
| Orthostatic hypotension | 1/113 (0.9%) | 1 | 0/103 (0%) | 0 |
| Hypertensive emergency | 0/113 (0%) | 0 | 1/103 (1%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| HF10 Therapy Plus CMM | CMM Alone | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/113 (0%) | 0/103 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Initial publication of the results will be a joint, multicenter publication with all PIs and sites contributing data, analyses, and critical review of the manuscript. If no such publication occurs within 12 months of study completion, individual PIs may publish results from their center. PIs will allow sponsor 30 days to review any potential publications or presentations and sponsor can request an additional 60 days if needed.
Results Point of Contact
| Name/Title | Donald Middlebrook |
|---|---|
| Organization | Nevro Corp. |
| Phone | (650) 433-2218 |
| don.middlebrook@nevro.com |
- CA2016-5