Chronic Non-malignant Pain, Chronic Pain, Pain, Back, Pain, Leg
Conditions
Keywords
Pain, Intrathecal, Targeted Drug Delivery (TDD), Non-Malignant Pain, Systemic Opioids, Opioid Weaning, Pain Pump, Drug Pump, Medtronic Pump
Brief summary
This is a prospective, multi-center, post market study to evaluate Intrathecal (IT) preservative-free morphine sulfate (PFMS) using the SynchroMed™ II infusion system as an alternative to systemic opioids for the treatment of chronic, intractable, non-malignant primary back pain with or without leg pain.
Detailed description
Subjects will be assessed for pain control and opioid-related side effects following a route of delivery change from systemic opioids to IT morphine therapy.
Interventions
DEVICEMedtronic SynchroMed™ II infusion system
Implanted infusion system consisting of a pump and catheter, as well as external components of a clinician programmer, refill and catheter access port kits, and the Personal Therapy Manager (myPTM™).
DRUGPreservative-free morphine sulfate (PFMS)
The pharmacological agent used in the pump for this study is limited to a preservative-free morphine sulfate (PFMS).
Sponsors
MedtronicNeuro
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willing and able to provide a signed and dated (Medtronic and Institutional Review Board (IRB) approved) Informed Consent Form (ICF) and Health Insurance Portability and Accountability Act (HIPAA) Authorization Form prior to any study procedures being performed 2. A candidate per labeling for the Intrathecal Drug Delivery System (IDDS) 3. A diagnosis of chronic, intractable, non-malignant primary back pain with or without leg pain, treatable with the IDDS 4. Current daily systemic opioid dose of \>0 and ≤ 120 Morphine Milligram Equivalents (MME) 5. A Visual Analogue Scale (VAS) of ≥50 mm for pain intensity at the Baseline Visit and/or a Numerical Opioid Side Effect (NOSE) Assessment Tool ≥40 for intolerable side effects at the Baseline Visit 6. Psychological evaluation or investigator assessment of patient psychological suitability for study participation 7. Has an MRI or CT prior to enrollment verifying patent spinal canal and no clinical change in status since last imaging 8. At least 18 years old at time of enrollment 9. Willing and able to attend visits and comply with the study protocol 10. Male or non-pregnant, non-lactating female. Females must be post-menopausal or surgically sterile; or be utilizing a medically acceptable form of birth control (i.e. a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, or condom with spermicide) for the duration of the study
Exclusion criteria
1. Previously trialed or implanted with an IDDS 2. Concomitant stimulation device implanted for the treatment of pain 3. Any ongoing health condition that would be expected to interfere with pain and/or quality of life ratings (i.e. active malignancy, other painful conditions not treatable with IT therapy, etc.) 4. Psychological or other health conditions, financial and/or legal concerns that would interfere with the subject's ability to fulfill the requirements of the protocol as per the investigator's discretion 5. Substance Use Disorder (SUD) within the last 2 years or current Medication Assisted Treatment (MAT) for substance use disorder 6. Currently using cannabinoids or illicit drugs 7. History of allergy or significant adverse reaction to morphine per investigator discretion 8. Currently participating or plans to participate in another investigational study unless written approval is provided by Medtronic Study Team
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Success at the 6-Month Visit | Baseline to 6-Month Visit | To characterize the number of subjects with Clinical Success at the 6-Month Visit. Clinical Success is defined as any of the following: 1) Reduced opioid-related side effects (at least a 20% reduction) with equal pain (less than 20% increase or decrease) 2) Reduced pain (at least a 20% reduction) with equal opioid-related side effects (less than 20% increase or decrease) 3) Reduced pain and reduced opioid-related side effects (at least a 20% reduction in both). The number of subjects with Clinical Success at the 6-Month Visit is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analog Scale (VAS) Pain Intensity at the 6-Month Visit | Baseline to 6-Month Visit | To demonstrate pain intensity scores (Visual Analog Scale, VAS) at the 6-Month Visit is non-inferior to VAS at Baseline, with a non-inferiority margin of 10mm. Pain was assessed using a Visual Analog Scale, ranging from 0-100, where 0 is no pain and 100 is the worst pain. The VAS is a 100mm line, with No pain on the left side of the line and Worst pain imaginable on the right side of the line. Subjects made a perpendicular mark on the VAS line that best describes their average pain in the last 24 hours. Change in VAS is calculated as 6-Months - Baseline, with a negative change indicating a reduction (i.e., improvement) in pain intensity. |
| Numerical Opioid Side Effect (NOSE) Assessment Tool | Baseline to 6-Month Visit | To characterize the change in opioid-related side effects scores (NOSE) from Baseline to the 6-Month Visit. The Numerical Opioid Side Effect (NOSE) Assessment Tool is a tool to evaluate 10 opioid-related side effects using a 11-point numerical scale. Subjects are asked to evaluate each of the 10 opioid-related side effects on a scale of 0 - 10 with 0 being not present and 10 being as bad as you can imagine. A total sum score can range from 0 - 100, where 0 is no opioid-related side effects and 100 is the worst opioid-related side effects. Change in NOSE is calculated as 6-Months - Baseline, with a negative change indicating a reduction (i.e., improvement) in opioid-related side effects. |
| Number of Participants With Systemic Opioid Elimination Through the 6-Month Visit | Baseline to 6-Month Visit | To characterize the number of subjects who eliminate systemic opioids through the 6-Month Visit. Four drug tests for systemic opioid use are administered from intrathecal therapy initiation through the 6-Month Visit. If all of the available drug tests are negative for systemic opioid use, the subject is counted as eliminating systemic opioids through the 6-Month Visit. The number of subjects who eliminated systemic opioids through the 6-Month Visit is presented. |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled from 2019 through 2021 at 16 sites.
Pre-assignment details
Subjects are considered enrolled at the time the informed consent form is signed. At the Baseline Visit, consented subjects are assessed for eligibility to the study-specific inclusion and exclusion criteria. Subjects who meet all eligibility criteria begin the systemic opioid weaning process prior to initiating the intrathecal drug trial. Subjects with a successful intrathecal trial are eligible for an Intrathecal Drug Delivery System Implant. Non-implanted subjects are exited from the study.
Participants by arm
| Arm | Count |
|---|---|
| Targeted Drug Delivery Subjects All subjects implanted with the Intrathecal Drug Delivery System (IDDS). Subjects were treated via the IDDS with intrathecal preservative-free morphine sulfate (IT PFMS), at a concentration not exceeding 25 mg/mL and 0.9% solution of preservative-free sodium chloride injection (USP) for dilution. IT PFMS initiation and subsequent dosing adjustments were determined based on specific patient needs and clinician standard practices, with the goal to maintain or improve pain control and/or opioid-related side effects (compared to Baseline) with utilization of the lowest reasonable daily dose of IT PFMS. The following IT PFMS dose initiation parameters were recommended: (1) A starting PFMS dose of 0.1 to 0.5 mg/day, or half the effective trial dose, with lower initial PFMS doses considered, and (2) a starting concentration to achieve an estimated pump refill interval of 120 days, but not to exceed 180 days. IT PFMS dose increases or decreases could be made any time throughout the duration of study. | 52 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| 6 Months to 12 Months | Completed Study under Protocol v3 | 25 |
| 6 Months to 12 Months | Physician Decision | 2 |
| 6 Months to 12 Months | Withdrawal by Subject | 1 |
| Enrollment to Implant | Physician Decision | 2 |
| Enrollment to Implant | Screen Failure | 17 |
| Enrollment to Implant | Site Closure | 3 |
| Enrollment to Implant | Sponsor Request | 2 |
| Enrollment to Implant | Withdrawal by Subject | 17 |
| Post-Implant to 6 Months | Adverse Event | 2 |
| Post-Implant to 6 Months | Death | 1 |
| Post-Implant to 6 Months | Site Closure | 2 |
Baseline characteristics
| Characteristic | Targeted Drug Delivery Subjects |
|---|---|
| Age, Continuous | 63.1 years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Numerical Opioid Side Effect Assessment (NOSE, 0-100) | 21.3 units on a scale STANDARD_DEVIATION 20.4 |
| Pain (Visual Analog Scale, VAS, 0-100) | 75.5 units on a scale STANDARD_DEVIATION 13.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 47 Participants |
| Region of Enrollment United States | 52 participants |
| Sex: Female, Male Female | 39 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 93 |
| other Total, other adverse events | 18 / 93 |
| serious Total, serious adverse events | 20 / 93 |
Outcome results
Primary
Number of Participants With Clinical Success at the 6-Month Visit
To characterize the number of subjects with Clinical Success at the 6-Month Visit. Clinical Success is defined as any of the following: 1) Reduced opioid-related side effects (at least a 20% reduction) with equal pain (less than 20% increase or decrease) 2) Reduced pain (at least a 20% reduction) with equal opioid-related side effects (less than 20% increase or decrease) 3) Reduced pain and reduced opioid-related side effects (at least a 20% reduction in both). The number of subjects with Clinical Success at the 6-Month Visit is presented.
Time frame: Baseline to 6-Month Visit
Population: A subset of the Targeted Drug Delivery Subjects who maintained intrathecal morphine monotherapy (ITMM) and provided outcome data at both the Baseline and 6-Month (6M) Visit. Of the 52 implanted subjects, 47 completed the 6M Visit, and 42 maintained ITMM through the 6M Visit. Four of the subjects who did not maintain ITMM through the 6M Visit changed their intrathecal medication, and one subject was explanted prior to the 6M Visit and completed the 6M Visit post-explant.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Targeted Drug Delivery Subjects | Number of Participants With Clinical Success at the 6-Month Visit | 25 Participants |
Secondary
Number of Participants With Systemic Opioid Elimination Through the 6-Month Visit
To characterize the number of subjects who eliminate systemic opioids through the 6-Month Visit. Four drug tests for systemic opioid use are administered from intrathecal therapy initiation through the 6-Month Visit. If all of the available drug tests are negative for systemic opioid use, the subject is counted as eliminating systemic opioids through the 6-Month Visit. The number of subjects who eliminated systemic opioids through the 6-Month Visit is presented.
Time frame: Baseline to 6-Month Visit
Population: The subset of Targeted Drug Delivery Subjects who have a drug test at the 6-Month Visit and no more than 1 missing drug test through the 6-Month Visit. Of the 52 implanted subjects, 47 completed the 6M Visit, 42 maintained ITMM through the 6M Visit, and 41 completed a drug test at the 6-Month and had no more than 1 missing drug test through the 6-Month Visit.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Targeted Drug Delivery Subjects | Number of Participants With Systemic Opioid Elimination Through the 6-Month Visit | 31 Participants |
Secondary
Numerical Opioid Side Effect (NOSE) Assessment Tool
To characterize the change in opioid-related side effects scores (NOSE) from Baseline to the 6-Month Visit. The Numerical Opioid Side Effect (NOSE) Assessment Tool is a tool to evaluate 10 opioid-related side effects using a 11-point numerical scale. Subjects are asked to evaluate each of the 10 opioid-related side effects on a scale of 0 - 10 with 0 being not present and 10 being as bad as you can imagine. A total sum score can range from 0 - 100, where 0 is no opioid-related side effects and 100 is the worst opioid-related side effects. Change in NOSE is calculated as 6-Months - Baseline, with a negative change indicating a reduction (i.e., improvement) in opioid-related side effects.
Time frame: Baseline to 6-Month Visit
Population: A subset of the Targeted Drug Delivery Subjects who maintained intrathecal morphine monotherapy (ITMM) and provided outcome data at both the Baseline and 6-Month (6M) Visit. Of the 52 implanted subjects, 47 completed the 6M Visit, and 42 maintained ITMM through the 6M Visit. Four of the subjects who did not maintain ITMM through the 6M Visit changed their intrathecal medication, and one subject was explanted prior to the 6M Visit and completed the 6M Visit post-explant.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Targeted Drug Delivery Subjects | Numerical Opioid Side Effect (NOSE) Assessment Tool | -9.4 score on a scale |
Secondary
Visual Analog Scale (VAS) Pain Intensity at the 6-Month Visit
To demonstrate pain intensity scores (Visual Analog Scale, VAS) at the 6-Month Visit is non-inferior to VAS at Baseline, with a non-inferiority margin of 10mm. Pain was assessed using a Visual Analog Scale, ranging from 0-100, where 0 is no pain and 100 is the worst pain. The VAS is a 100mm line, with No pain on the left side of the line and Worst pain imaginable on the right side of the line. Subjects made a perpendicular mark on the VAS line that best describes their average pain in the last 24 hours. Change in VAS is calculated as 6-Months - Baseline, with a negative change indicating a reduction (i.e., improvement) in pain intensity.
Time frame: Baseline to 6-Month Visit
Population: A subset of the Targeted Drug Delivery Subjects who maintained intrathecal morphine monotherapy (ITMM) and provided outcome data at both the Baseline and 6-Month (6M) Visit. Of the 52 implanted subjects, 47 completed the 6M Visit, and 42 maintained ITMM through the 6M Visit. Four of the subjects who did not maintain ITMM through the 6M Visit changed their intrathecal medication, and one subject was explanted prior to the 6M Visit and completed the 6M Visit post-explant.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Targeted Drug Delivery Subjects | Visual Analog Scale (VAS) Pain Intensity at the 6-Month Visit | -15 units on a scale |
Comparison: This analysis was to demonstrate pain intensity scores (VAS) at the 6-Month Visit is non-inferior to VAS at Baseline, i.e., the change in pain intensity is not greater than 0 by more than 10 points from Baseline to the 6-Month Visit.p-value: <0.001Wilcoxon Signed Rank test
Comparison: This analysis was to demonstrate pain intensity scores (VAS) at the 6-Month Visit are less than VAS at Baseline, i.e., the reduction in pain intensity is less than 0 from Baseline to the 6-Month Visit.p-value: <0.00195% CI: [-22.7, -7.1]Wilcoxon Signed Rank test