Embrace TDD: Post-Market Study to Evaluate Intrathecal Morphine as an Alternative to Systemic Opioids for Chronic Pain

Embrace TDD: Prospective, Multi-Center, Post Market Study to Evaluate Intrathecal (IT) Morphine as an Alternative to Systemic Opioids for the Treatment of Chronic, Intractable, Non-Malignant Primary Back Pain With or Without Leg Pain

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.

Study Overview

• Status: Completed
• Conditions: Chronic Pain; Pain, Back; Chronic Non-malignant Pain; Pain, Leg
• Intervention / Treatment: Device: Medtronic SynchroMed™ II infusion system; Drug: Preservative-free morphine sulfate (PFMS)

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.

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Neuroversion
  • California
    • Carlsbad, California, United States, 92009
      • Coastal Pain and Spinal Diagnostics
    • Napa, California, United States, 94558
      • Napa Valley Orthopaedic Medical Group
  • Florida
    • Merritt Island, Florida, United States, 32935
      • Florida Pain Institute
  • Missouri
    • Cape Girardeau, Missouri, United States, 63701
      • Regional Brain & Spine, LLC
    • Saint Louis, Missouri, United States, 63136
      • Christian Hospital Pain Management
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Comprehensive and Interventional Pain Management
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • The Pain Management Center
  • Ohio
    • Mount Orab, Ohio, United States, 45154
      • Premier Pain Treatment Institute
  • Oklahoma
    • Edmond, Oklahoma, United States, 73013
      • Clinical Investigations, LLC
  • Pennsylvania
    • Elkins Park, Pennsylvania, United States, 19027
      • Moss Rehabilitation-Einstein Healthcare Network
  • Texas
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch
    • Tyler, Texas, United States, 75701
      • Precision Spine Care
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Pain Management Center
    • Norfolk, Virginia, United States, 23507
      • Eastern Virginia Medical School
  • Washington
    • Spokane, Washington, United States, 99201
      • Northwest Pain Care, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

OTHER: Intrathecal Therapy; Enrolled subjects who successfully wean from all systemic opioids and have a successful intrathecal trial, proceed to the intervention phase. This includes implantation with a SynchroMed™ II infusion system in the intrathecal space for targeted drug delivery of preservative-free morphine sulfate (PFMS).

Device: Medtronic 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™).; Drug: Preservative-free morphine sulfate (PFMS); The pharmacological agent used in the pump for this study is limited to a preservative-free morphine sulfate (PFMS).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to 6-Month Visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to 6-Month Visit
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.	Baseline to 6-Month Visit
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.	Baseline to 6-Month Visit

Collaborators and Investigators

• Sponsor: MedtronicNeuro

Publications and helpful links

General Publications

• Smith TJ, Staats PS, Deer T, Stearns LJ, Rauck RL, Boortz-Marx RL, Buchser E, Catala E, Bryce DA, Coyne PJ, Pool GE; Implantable Drug Delivery Systems Study Group. Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management for refractory cancer pain: impact on pain, drug-related toxicity, and survival. J Clin Oncol. 2002 Oct 1;20(19):4040-9. doi: 10.1200/JCO.2002.02.118.
• Hamza M, Doleys D, Wells M, Weisbein J, Hoff J, Martin M, Soteropoulos C, Barreto J, Deschner S, Ketchum J. Prospective study of 3-year follow-up of low-dose intrathecal opioids in the management of chronic nonmalignant pain. Pain Med. 2012 Oct;13(10):1304-13. doi: 10.1111/j.1526-4637.2012.01451.x. Epub 2012 Jul 30.
• Grider JS, Etscheidt MA, Harned ME, Lee J, Smith B, Lamar C, Bux A. Trialing and Maintenance Dosing Using a Low-Dose Intrathecal Opioid Method for Chronic Nonmalignant Pain: A Prospective 36-Month Study. Neuromodulation. 2016 Feb;19(2):206-19. doi: 10.1111/ner.12352. Epub 2015 Oct 19.
• Hamza M, Doleys DM, Saleh IA, Medvedovsky A, Verdolin MH, Hamza M. A Prospective, Randomized, Single-Blinded, Head-to-Head Long-Term Outcome Study, Comparing Intrathecal (IT) Boluses With Continuous Infusion Trialing Techniques Prior to Implantation of Drug Delivery Systems (DDS) for the Treatment of Severe Intractable Chronic Nonmalignant Pain. Neuromodulation. 2015 Oct;18(7):636-48; discussion 649. doi: 10.1111/ner.12342. Epub 2015 Aug 26.
• Wilkes DM, Orillosa SJ, Hustak EC, Williams CG, Doulatram GR, Solanki DR, Garcia EA, Huang LM. Efficacy, Safety, and Feasibility of the Morphine Microdose Method in Community-Based Clinics. Pain Med. 2018 Sep 1;19(9):1782-1789. doi: 10.1093/pm/pnx132.
• Grider JS, Harned ME, Etscheidt MA. Patient selection and outcomes using a low-dose intrathecal opioid trialing method for chronic nonmalignant pain. Pain Physician. 2011 Jul-Aug;14(4):343-51.

Helpful Links

• Applicable Product Manual(s) for the SynchroMed II infusion system

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 16, 2019
• Primary Completion (ACTUAL): December 6, 2021
• Study Completion (ACTUAL): December 6, 2021

Study Registration Dates

• First Submitted: November 15, 2018
• First Submitted That Met QC Criteria: November 29, 2018
• First Posted (ACTUAL): December 3, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: January 13, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Pain; Intrathecal; Targeted Drug Delivery (TDD); Non-Malignant Pain; Systemic Opioids; Opioid Weaning; Pain Pump; Drug Pump; Medtronic Pump
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain; Chronic Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Morphine
• Other Study ID Numbers: MDT18026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No