Chronic Lower Limb Pain
Conditions
Brief summary
The purpose of this study is to evaluate the safety and effectiveness of the AXIUM Neurostimulator System for the treatment of chronic lower limb pain in persons diagnosed with Complex Regional Pain Syndrome (CRPS) or Peripheral Causalgia (PC).
Detailed description
The ACCURATE study is a prospective, randomized, controlled, multicenter clinical trial designed to assess the safety and efficacy of the Spinal Modulation Axium Neurostimulator System as an aid in the management of chronic, intractable pain of the lower limbs, including unilateral or bilateral pain associated with one of the following conditions: Complex Regional Pain Syndrome (CRPS) or Peripheral Causalgia (also referred to as CRPS Type II). Enrolled subjects were diagnoses with CRPS or peripheral causalgia; experienced pain for at least six months; and failed to achieve adequate pain relief from at least two prior pharmacologic treatments. All subjects had a temporary trial neurostimulator (TNS). If the subject was a treatment success at the end of TNS they were scheduled for the fully implantable neurostimulator (INS) implant procedure. If not, subjects were exited from the study.
Interventions
DEVICEAXIUM Neurostimulator System
DEVICEControl Spinal Cord Stimulation Device
Sponsors
Abbott Medical Devices
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
22 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Subject is male or female between the ages of 22 and 75 years 2. Subject is able and willing to comply with the follow-up schedule and protocol 3. Subject has chronic, intractable pain of the lower limb(s) for at least 6 months 4. Subjects are diagnosed with complex regional pain syndrome (CRPS) and/or peripheral causalgia 5. Subjects have a minimum Visual Analog Scale (VAS) greater than or equal to 60 mm in the area of greatest pain in the lower limbs. 6. Subject has failed to achieve adequate pain relief from at least 2 prior pharmacologic treatments from at least 2 different drugs classes 7. Subject has had stable neurologic function in the past 30 days 8. In the opinion of the Investigator, the subject is psychologically appropriate for the implantation of an active implantable medical device 9. Subject is able to provide written informed consent
Exclusion criteria
1. Back pain is the greatest region of pain as measured on the baseline VAS. 2. Female subject of childbearing potential is pregnant/nursing, plans to become pregnant or is unwilling to use approved birth control 3. Subject has exhibited escalating or changing pain condition within the past 30 days as evidenced by Investigator examination 4. Subject is currently involved in medically related litigation, including workers compensation 5. Subject has had corticosteroid therapy at an intended site of stimulation within the past 30 days 6. Subject's pain medication(s) dosage(s) are not stable for at least 30 days 7. Subject has had radiofrequency treatment of an intended target Dorsal Root Ganglion within the past 3 months 8. Subject has previously failed spinal cord stimulation therapy 9. Subject currently has an active implantable device including implantable cardioverter defibrillator, pacemaker, spinal cord stimulator or intrathecal drug pump or subject requires magnetic resonance imaging (MRIs) or diathermy 10. Subject has pain only within a cervical distribution 11. Subject has cognitive, physical or sensory impairment that, in the opinion of the Investigator, may limit their ability to operate the device 12. Subject currently has an indwelling device that may pose an increased risk of infection 13. Subject currently has an active systemic infection. 14. Subject has, in the opinion of the investigator, a medical comorbidity that contraindicates placement of an active medical device 15. Subject has participated in another clinical investigation within 30 days 16. Subject has a coagulation disorder or uses anticoagulants that, in the opinion of the Investigator, precludes participation 17. Subject has been diagnosed with cancer in the past 2 years 18. Imaging (MRI, CT, x-ray) findings within the last 12 months that, in the Investigator's opinion, contraindicates lead placement 19. Subject is a prisoner
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Composite Endpoint - Treatment Success | 3 months | Treatment Success is defined as at least 50% lower limb pain relief (VAS score reduction) at the end of trial phase, received at least 50% lower limb pain relief at the 3-month visit post implant, and the absence of a stimulation related neurological deficit. Pain scores were measured using Visual Analog Scale (VAS). The VAS score ranges from 0-100 mm with a higher score indicating higher pain intensity ( 0 representing No Pain and 100 mm representing Worst Imaginable Pain). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Positional Effects on Paresthesia Intensities | 3 months | Positional effects on paresthesia intensities at 3 months in the Control group versus the Treatment Group. This endpoint will compare the difference in paresthesia scores upright and supine between the AXIUM and Control groups. Paresthesia intensity was rated by subjects using a paresthesia intensity rating scale. Subjects rated the intensity of their perception of paresthesia, while upright and supine, on an 11-point numeric rating scale from 0 representing No feeling to 10 Very intense. Perceived paresthesia intensity difference between supine and upright positions was calculated and averaged across each group. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Primary Composite Endpoint - Treatment Success for Only Those Subjects With a Permanent Implant | 3 months | Treatment Success is defined as a reduction in pain score greater than or equal to 50 percent and the absence of a stimulation related neurological deficit. Pain scores were measured using Visual Analog Scale (VAS). The VAS score ranges from 0-100 mm with a higher score indicating higher pain intensity ( 0 representing No Pain and 100 mm representing Worst Imaginable Pain). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AXIUM Neurostimulator System The AXIUM Neurostimulator System is an investigational spinal cord stimulation device that is designed to stimulate the dorsal root ganglion (DRG) of the spine located on the back surface of the spinal cord where nerves exit the backbone. The device has 2 parts that are placed surgically (implanted) : 1) a pulse generator which is placed under the skin in the buttocks or abdomen, and 2) up to four wires (leads) that have one end attached to the pulse generator, and the other end secured to the tissue near the target treatment area.
AXIUM Neurostimulator System | 76 |
| Control Spinal Cord Stimulation Device The Control Spinal Cord Stimulation Device is a commercially available spinal cord stimulator indicated for the treatment of chronic lower limb pain.
Control Spinal Cord Stimulation Device | 76 |
| Total | 152 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 7 | 6 |
Baseline characteristics
| Characteristic | AXIUM Neurostimulator System | Control Spinal Cord Stimulation Device | Total |
|---|---|---|---|
| Age, Continuous | 53.2 Years | 53 Years | 53 Years |
| Body Mass Index (BMI) | 29.9 kg/m2 | 27.9 kg/m2 | 29.9 kg/m2 |
| Duration of Lower Limb Pain | 5.0 Years | 4.5 Years | 5.0 Years |
| Primary Diagnosis Complex Regional Pain Syndrome | 44 Participants | 43 Participants | 87 Participants |
| Primary Diagnosis Peripheral Causalgia | 32 Participants | 33 Participants | 65 Participants |
| Primary Region of Pain Region 2 - Right Groin | 4 Participants | 2 Participants | 6 Participants |
| Primary Region of Pain Region 3 - Left Groin | 4 Participants | 7 Participants | 11 Participants |
| Primary Region of Pain Region 4 - Right Buttock | 2 Participants | 2 Participants | 4 Participants |
| Primary Region of Pain Region 5 - Left Buttock | 1 Participants | 2 Participants | 3 Participants |
| Primary Region of Pain Region 6 - Right Leg | 14 Participants | 16 Participants | 30 Participants |
| Primary Region of Pain Region 7 - Left Leg | 8 Participants | 11 Participants | 19 Participants |
| Primary Region of Pain Region 8 - Right Foot | 21 Participants | 19 Participants | 40 Participants |
| Primary Region of Pain Region 9 - Left Foot | 22 Participants | 17 Participants | 39 Participants |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 4 Participants | 8 Participants | 12 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 72 Participants | 68 Participants | 140 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Black or African American | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Race White | 72 Participants | 70 Participants | 142 Participants |
| Region of Enrollment United States | 76 participants | 76 participants | 152 participants |
| Sex: Female, Male Female | 39 Participants | 37 Participants | 76 Participants |
| Sex: Female, Male Male | 37 Participants | 39 Participants | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 76 | 0 / 76 |
| other Total, other adverse events | 5 / 76 | 5 / 76 |
| serious Total, serious adverse events | 8 / 76 | 15 / 76 |
Outcome results
Primary
Primary Composite Endpoint - Treatment Success
Treatment Success is defined as at least 50% lower limb pain relief (VAS score reduction) at the end of trial phase, received at least 50% lower limb pain relief at the 3-month visit post implant, and the absence of a stimulation related neurological deficit. Pain scores were measured using Visual Analog Scale (VAS). The VAS score ranges from 0-100 mm with a higher score indicating higher pain intensity ( 0 representing No Pain and 100 mm representing Worst Imaginable Pain).
Time frame: 3 months
Population: Subjects excluded since they do not have evaluable data: Axium=4, Control=3. Seven subjects in the MITT analysis have no evaluable data for the study endpoints due to withdrawing prior to the 3-mo study visit and did not meeting criteria for treatment failure/success upon study exit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AXIUM Neurostimulator System | Primary Composite Endpoint - Treatment Success | 81.2 percentage of subjects |
| Control Spinal Cord Stimulation Device | Primary Composite Endpoint - Treatment Success | 55.7 percentage of subjects |
Comparison: The primary hypothesis tested was: H0: p1 ≤ p0 - δ vs. H1: p1\> p0 - δ, where p0 is the success rate in the Control group, p1 is the success rate in the Axium group, and δ is the non-inferiority margin, which is pre-specified at 10%.~If non-inferiority is achieved at a one-sided alpha of 0.05, a one-sided superiority test is performed at the significance level of 0.025.p-value: <0.0001Chi-squared
Comparison: The primary hypothesis tested was: H0: p1 ≤ p0 - δ vs. H1: p1\> p0 - δ, where p0 is the success rate in the Control group, p1 is the success rate in the Axium group, and δ is the non-inferiority margin, which is pre-specified at 10%.p-value: =0.0004Chi-squared
Secondary
Positional Effects on Paresthesia Intensities
Positional effects on paresthesia intensities at 3 months in the Control group versus the Treatment Group. This endpoint will compare the difference in paresthesia scores upright and supine between the AXIUM and Control groups. Paresthesia intensity was rated by subjects using a paresthesia intensity rating scale. Subjects rated the intensity of their perception of paresthesia, while upright and supine, on an 11-point numeric rating scale from 0 representing No feeling to 10 Very intense. Perceived paresthesia intensity difference between supine and upright positions was calculated and averaged across each group.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AXIUM Neurostimulator System | Positional Effects on Paresthesia Intensities | -0.1 score on a scale | Standard Deviation 1.6 |
| Control Spinal Cord Stimulation Device | Positional Effects on Paresthesia Intensities | 1.8 score on a scale | Standard Deviation 3 |
Comparison: Secondary endpoint compared the mean differences in upright and supine paresthesia scores between the Axium and Control groups at three months post INS implant. This endpoint was evaluated at a two-sided significance level of 0.05.~The primary hypothesis tested was: H0: μ0- μ1≤0 vs. H1: μ0- μ1\>0 where μ0 is the mean difference in paresthesia intensities in the Control group and μ1 is the mean difference in the Axium group.p-value: <0.000195% CI: [1, 2.8]Wilcoxon (Mann-Whitney)
Other Pre-specified
Primary Composite Endpoint - Treatment Success for Only Those Subjects With a Permanent Implant
Treatment Success is defined as a reduction in pain score greater than or equal to 50 percent and the absence of a stimulation related neurological deficit. Pain scores were measured using Visual Analog Scale (VAS). The VAS score ranges from 0-100 mm with a higher score indicating higher pain intensity ( 0 representing No Pain and 100 mm representing Worst Imaginable Pain).
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AXIUM Neurostimulator System | Primary Composite Endpoint - Treatment Success for Only Those Subjects With a Permanent Implant | 93.3 percentage of subjects |
| Control Spinal Cord Stimulation Device | Primary Composite Endpoint - Treatment Success for Only Those Subjects With a Permanent Implant | 72.2 percentage of subjects |
Comparison: The primary hypothesis tested was: H0: p1 ≤ p0 - δ vs. H1: p1\> p0 - δ, where p0 is the success rate in the Control group, p1 is the success rate in the Axium group, and δ is the non-inferiority margin, which is pre-specified at 10%.p-value: <0.0001Chi-squared
p-value: =0.0047Chi-squared
Other Pre-specified
Primary Composite Endpoint - Treatment Success for Only Those Subjects With a Permanent Implant
Treatment Success is defined as a reduction in pain score greater than or equal to 50 percent and the absence of a stimulation related neurological deficit. Pain scores were measured using Visual Analog Scale (VAS). The VAS score ranges from 0-100 mm with a higher score indicating higher pain intensity ( 0 representing No Pain and 100 mm representing Worst Imaginable Pain).
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AXIUM Neurostimulator System | Primary Composite Endpoint - Treatment Success for Only Those Subjects With a Permanent Implant | 86 percentage of subjects |
| Control Spinal Cord Stimulation Device | Primary Composite Endpoint - Treatment Success for Only Those Subjects With a Permanent Implant | 68.6 percentage of subjects |
Comparison: The primary hypothesis tested was: H0: p1 ≤ p0 - δ vs. H1: p1\> p0 - δ, where p0 is the success rate in the Control group, p1 is the success rate in the Axium group, and δ is the non-inferiority margin, which is pre-specified at 10%.p-value: 0.0003Non-inferiority