Intrathecal Morphine Compared to Conventional Medical Management for Pain Control and Opioid-related Side Effects

Study Overview
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Brief Summary
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This study compares two different ways to treat pain. The two ways are: continuing to take current pain medication(s) or receiving morphine, a pain medication from a drug pump (a system to deliver drug to your body) that is implanted. None of the procedures or products used in this study are experimental. The length the study will be about 25 weeks (between 5½ to 6½ months). The purpose of this study is to compare pain and opioid side effects between people who get a drug pump and people who do not get a drug pump that will stay on their current pain medication treatment.

Detailed Description
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This was a randomized, controlled, open-label, multi-center, prospective post-market study to assess pain control and opioid-related side effects following a route of delivery change to low dose IT morphine therapy from systemic opioid therapy. Subjects with nonmalignant, chronic, intractable pain who were experiencing inadequate pain relief and/or intolerable side effects from systemic opioid therapy receiving ≤300 mg/day morphine equivalent dose were eligible for screening. Additionally, the subjects had no known history of sleep apnea and were candidates for IT morphine administration via the SynchroMed Infusion System. Subjects must not have previously undergone an intrathecal/epidural trial for pump infusion therapy.

Official Title
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Post-market Study Evaluating a Treatment Conversion to Low Dose Intrathecal Morphine From Conventional Medical Management for Maintenance of Pain Control and Improvement of Opioid-related Side Effects. (CONVERT Targeted Drug Delivery [TDD])

Conditions
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Chronic Pain

Intervention / Treatment
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* Device: SynchroMed Infusion System and Intrathecal Morphine Sulfate
* Other: Conventional Medicine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated Medtronic/IRB approved Informed Consent Form and HIPAA Authorization prior to any study procedures being performed Willing and able to attend visits and comply with the study protocol Willing and able to abstain from alcohol consumption for the study duration At least 18 years of age Male or non-pregnant, non-lactating female Currently receiving </= 300 mg/day morphine equivalent of systemic opioids at screening Used a stable dose of opioids (no change in type or prescribed frequency or dose) for 30 days prior to the Screening as documented in the medical history Used chronic systemic opioids for at least 6 months prior to Screening as documented in medical history Per investigator's medical assessment and the subject's medical history, the subject is/has: A new candidate for chronic intrathecal drug therapy (including no prior intrathecal/epidural trial for pump infusion therapy) A diagnosis of nonmalignant, chronic intractable pain as documented in the medical history Medically stable and able to undergo surgery for implantation of the SynchroMed Infusion System Completed a psychological evaluation within 6 months prior to Screening Exclusion Criteria: Psychological or other health conditions, financial, and/or legal concerns (within 3 months prior to Screening) that would interfere with the subject's ability to fulfill the requirements of the protocol as per the investigator's opinion A history of alcohol abuse or any illicit drug use within 2 years prior to Screening A positive urine test for illicit drugs at Screening (Exception: If subject has a physician's prescription for an illicit drug; for example, medical marijuana) Known diagnosis of moderate to severe sleep apnea. Prescribed Continuous Positive Airway Pressure (CPAP), Adaptive Servo-Ventilation (ASV) therapy or an oral appliance prescribed for the treatment of moderate to severe sleep apnea (current or previous history) An active malignancy or has been diagnosed with cancer and has not been in remission for at least 1 year prior to screening An implanted electrical stimulation device(s) or if the subject is expected to require one of these during the course of the study Planned to enroll or is currently enrolled in another investigational drug or investigational medical device study or has participated in an investigational drug or medical device study within 30 days prior to Screening Prior to Randomization, a subject will be excluded if: Diary does not meet compliance Mean diary-reported 12-hour NPRS < 6 (on 0 to 10 scale, as reported over 5 days) Positive urine test for alcohol at Baseline Negative urine test for opioids at Baseline Baseline sleep study (PSG) with SaO2 <=80% for >= 5 consecutive minutes, and/or an Apnea-Hypopnea Index (AHI) >=15.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: IT group (Intrathecal Morphine Sulfate)<br>SynchroMed Infusion System and Intrathecal Morphine Sulfate | Device: SynchroMed Infusion System and Intrathecal Morphine Sulfate<br>* Following a successful test of Intrathecal Morphine Sulfate, subjects will undergo surgery to implant the drug pump (SynchroMed Infusion System) and spinal catheter. The pump will deliver morphine directly to the spinal cord for pain control.<br>* Other names: Intrathecal morphine;|
| Other: Conventional Medical Management<br>Conventional Medicine, and then SynchroMed Infusion System and Intrathecal Morphine Sulfate | Device: SynchroMed Infusion System and Intrathecal Morphine Sulfate<br>* Following a successful test of Intrathecal Morphine Sulfate, subjects will undergo surgery to implant the drug pump (SynchroMed Infusion System) and spinal catheter. The pump will deliver morphine directly to the spinal cord for pain control.<br>* Other names: Intrathecal morphine;Other: Conventional Medicine<br>* Subjects will continue to use pain medications as prescribed by their doctor.<br>* Other names: Standard of Care;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Success | Determine the proportion of subjects with clinical success based on changes in pain intensity (Numerical Pain Rating Scale: NPRS) and opioid-related Common Toxicity Criteria for Adverse Events (CTCAE) from the National Cancer Institute (NCI). | 3 Month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Assessment | Compare changes from Baseline to Month 3 between the IT group and CMM group in Numeric Pain Rating Scale (NPRS). The scale measures pain intensity. Using NPRS, a pain score ranging from 0 (no pain) to 10 (pain as bad as you can imagine) is recorded on a subject diary twice daily for 5 days before a study visit. The score for each visit is calculated as the mean pain of the 5 diary days morning and evening scores. For each subject, the change in pain will be calculated as the mean pain score at Month 3 minus the mean pain score at Baseline. A negative change value represents a lowering of the pain score (an improvement, or reduction in pain). | 3 Month | 
| Opioid-Related Side Effects | Summarize the changes from Baseline to Month 3 between the IT group and CMM group in Common Terminology Criteria for Adverse Events (CTCAE) toxicity score. (from the National Cancer Institute) A subset of 23 specific items of the CTCAE v4.03 were evaluated. The subset was chosen as these criteria were most related to opioid side effects that are of interest in this study. The investigator scored the assessment at each visit. The total score for a visit is based on the sum of 23 individual CTCAE's. The individual scales have a range of 0 to 2, 0 to 3, or 0 to 5 and the total score ranges from 0 (best case) to 90 (worst case). For each subject, the change in toxicity will be calculated as the total toxicity score at Month 3 minus the total toxicity score at Baseline. A negative change value represents a lowering of the subjects toxicity score (an improvement, or reduction in toxicity). | 3 Month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic pain, inadequate pain relief, intolerable side effects