Patient Controlled Intrathecal Analgesia With Bupivacaine for Chronic Low Back Pain

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the local anesthetic bupivacaine delivered intrathecally in small doses via PTM self-administered boluses significantly improves the breakthrough pain and functional status of patients with chronic intractable pain who are managed with an intrathecal drug delivery system.

Detailed Description
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Methodology /Technical Approach: Seventeen patients who are already using SynchroMed II pump containing an admixture of bupivacaine and an opioid and using PTM doses will receive Solution A during the first week of the study and will be crossed over to Solution B during the second week of the study. Solution A and Solution B would consist of either the patient's usual intrathecal opioid with bupivacaine at the same concentrations or the usual patient's intrathecal opioid at the same concentration but without bupivacaine. Only the Investigational Pharmacy at University Hospitals Case Medical Center (UHCMC) would be aware of the contents of Solution A and Solution B. Patients and study personnel in the Pain Medicine Division would be blinded to the solution content. The sequence of pump refills will be as follows: Week I: Patients will have the intrathecal pumps refilled with 10 milliliters of a Solution A or B, after removal of residual volume of baseline solution. Week II: IT pump will be filled with 10 ml of Solution A or B (whichever solution subject did not receive Week 1), after removal of residual volume from Week I. Both patients and the evaluating physician will be blinded. In order to accomplish this, only the central compounding (investigational) pharmacy at UHCMC would make two solutions labeled: A or B respectively. Study subjects will be randomized and randomization order will be held at the pharmacy that will supply the medication. Patients will be kept on each solution for one week. Data will be collected daily Primary outcome measures will include 0-10 numerical rating scale (NRS) or Visual Analogue Scale (VAS) both immediately before and within 30 minutes after a PTM bolus. Patients will be provided with a diary to record pain scores just before a PTM bolus and the lowest pain score within half an hour after a PTM bolus. Only 5 recording per day on days 3-7 and 10-14 will be available on the diary-thus patients would record pain scores only before and after the first 5 PTM boluses. Only the scores before and after the first 3 successful PTM boluses would be considered. Successful PTM activations would be determined by review of the patient PTM diary and the internal log from the intrathecal drug delivery system. Each recording on the PTM diary would be time matched to the successful PTM activation code in the internal log. This will obviate any potential mis-administered bolus whereby the patient does not activate the bolus device appropriately. Secondary outcome measures will include average NRS pain scores for the week, functional capacity as evaluated by the Oswestry disability index (ODI) scores, Global Impression of Change and painDETECT. Other relevant data such as number of boluses used and paresthetic sensation post bolus (if felt)/patient guess of blinding arm would be recorded.

Official Title
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Randomized, Double Blind, Cross Over Study Comparing Effectiveness of Traditional Opioids Versus Opioids in Admixture With Bupivacaine Upon Self-administration of Boluses Via a Personal Therapy Manager (PTM) in Intrathecal Pumps

Conditions
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Pain, Intractable, Breakthrough Pain, Chronic Pain

Intervention / Treatment
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* Drug: Bupivacaine
* Drug: Opioid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age more than 30 years implanted with an intrathecal drug delivery device. Intrathecal pump patients on stable dose for the last 3 months. Using on average more than 2 and less than 10 PTM doses per day Intrathecal medication admixture consisting of bupivacaine and another opioid (fentanyl or hydromorphone or morphine) Exclusion Criteria Using 10 or more PTM bolus doses per day or 2 or less PTM bolus doses per day Pending litigation or worker compensation claim Any recent (less than 3 month) procedures in spine (surgeries) or catheter adjustments. Recent pump dose adjustment within the past 3 months Pumps with medications other than bupivacaine/opioid combination. Pregnant or breast feeding

Ages Eligible for Study
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Minimum Age: 31 Years
Maximum Age: 90 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bupivacaine + Opioid<br>Intrathecal solution has bupivacaine with an opioid (hydromorphone, fentanyl or morphine). Patients will administer PTM bolus of bupivacaine with opioid. The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be >2 and <10. The bupivacaine dosage would range between 0.4 and 1.5 mg per bolus. The opioid dose will vary depending on the concentration of the opioid in the solution. | Drug: Bupivacaine<br>* Patient-activated intrathecal bolus for incident pain<br>Drug: Opioid<br>* Patient-activated intrathecal bolus for incident pain<br>* Other names: Morphine;|
| Active Comparator: Opioid<br>Intrathecal solution has only an opioid (hydromorphone, fentanyl or morphine) and no bupivacaine. Patients will administer PTM bolus of opioid without bupivacaine. This opioid bolus dose would be the same as they would have received prior to enrolling in the study (with bupivacaine). The bolus will be administered over 2 minutes and will have a variable frequency depending on patient's need but the number of boluses should be >2 and <10. | Drug: Opioid<br>* Patient-activated intrathecal bolus for incident pain<br>* Other names: Morphine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Numerical Rating Pain Scale (NRS) | Patients will be provided with a diary to record pain scores just before a PTM bolus and the lowest pain score within half an hour after a PTM bolus. Numerical Rating Pain Scale (NRS): scale from 0-10 0 = no pain 10 = worst imaginable pain | Before self-administered bolus using Patient Therapy Manager device (PTM) and within 30 minutes of PTM bolus | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Oswestry Disability Index (ODI) | Oswestry Disability Index (ODI): calculated as a percentage based on scores from 0-5 in 10 categories (pain intensity, personal care, lifting, walking, sitting, standing, sleeping, sex life, social life, travelling). 0 signifies no pain interference while 5 signifies maximum possible pain interference in the 10 categories. Scores from 0-5 for 10 categories are added and divided by total possible score (50) X 100 to give percentage. Interpretation of percentage scores: 0 - 20% minimal disability 21-40% moderate disability 41-60% severe disability 61-80% crippled 81-100% either bed bound or patient is exaggerating symptoms | Day 0, 7, 14, score at day 7 or day 14 reported | 
| Change From Baseline in Patient Global Impression of Change (PGIC) | Patient Global Impression of Change (PGIC): reflects patient's belief about the efficacy of treatment = very much improved = much improved = minimally improved = no change = worse = much worse = very much worse | Day 0, 7, 14, score at day 7 or day 14 reported | 
| Change From Baseline in painDETECT | painDETECT is a nine-item questionnaire that consists of seven sensory symptom items for pain that are graded from 0= never to 5= strongly, one temporal item on pain-course pattern graded -1 to +1, and one spatial item on pain radiation graded 0 for no radiation or +2 for radiating pain. A total score that ranges from -1 to 38 can be calculated from the nine items, with higher scores indicating higher levels of pain. | Day 0, 7, 14, score at day 7 or day 14 reported | 
| Change From Baseline in Average Weekly Numeric Pain Rating Score (NRS) | Average Weekly Numeric Pain Rating Score (NRS) over the past week Numerical Rating Pain Scale (NRS): scale from 0-10 0 = no pain 10 = worst imaginable pain | Day 0, 7, 14, score at day 7 or day 14 reported | 
| Change From Baseline in Treatment Satisfaction | A 5-point qualitative Likert scale was used to report measures of patient satisfaction (i.e., not satisfied at all, not satisfied, somewhat, satisfied, very satisfied). To quantify satisfaction, these responses were transformed to a scale of 0-4, with higher numbers representing greater levels of satisfaction. | Day 0, 7, 14, score at day 7 or day 14 reported |