Study to Examine Pain Relief With Supplemental Intrathecal Morphine in TKA Patients

Study Overview
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Brief Summary
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This is a prospective, randomized, double-blinded, placebo-controlled study designed to examine pain relief following intrathecal morphine sulfate (0.2mg) in patients undergoing total knee arthroplasty (TKA) under spinal anesthesia in addition to a femoral nerve catheter. The protocol consists of two parts: (1) a prospective patient recruitment study and (2) a retrospective assay for endocannabinoids on previously collected specimens.

Detailed Description
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This is a prospective, case-controlled randomized, double-blinded, placebo-controlled study expected to enroll up to 100 patients scheduled to undergo unilateral total knee arthroplasty (TKA) under regional anesthesia (defined as intrathecal spinal + femoral nerve blockade + femoral nerve catheter for post-operative analgesia) at Stony Brook Hospital. The patients were randomized to receive either IT morphine 0.2 mg (Group 1) or placebo (Group 2) in combination with their standard-of-care spinal anesthesia. Post-operatively, the patients were given an intravenous patient-controlled analgesic opioid for breakthrough pain. Only the pharmacist preparing the drug/placebo has knowledge of how each subject was randomized. Study staff completed multiple questionnaires regarding subjects' pain scores and patient disability from pain to assess changes between different study periods (ie. pre-operative, post-operative and follow up). Biological samples were also taken from each subject to measure and analyze differences and changes in endocannabinoid levels.

Official Title
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Prospective, Randomized, Double-blinded, Placebo-controlled Study to Examine Pain Relief and the Need for Supplementary Analgesics With Intra-thecal Morphine Sulfate (0.2 mg) in Patients Undergoing Total Knee Arthroplasty (TKA)

Conditions
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Acute Pain

Intervention / Treatment
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* Drug: Morphine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Scheduled for unilateral TKA under regional anesthesia ASA Class 1, 2 or 3 Able to give informed consent Able to understand English Exclusion Criteria: Medical condition(s) that prevents use of regional anesthesia (e.g. infection at site of injection, coagulopathy, severe hypovolemia, severe aortic or mitral stenosis, increased intracranial pressure, severe spinal deformity, spinal cord hardware or stimulator implanted) Allergy to morphine Morbid obesity (BMI > 45) Respiratory compromise (difficult airway, severe emphysema or COPD) Obstructive sleep apnea (only if diagnosed in a sleep disorders clinic and CPAP was prescribed) Chronic pain with opioid usage over 100 mg morphine-equivalents po/day History of abuse of opioids or other drugs of abuse Scheduled for bilateral TKA Revision of knee arthroplasty Any medical condition that would affect the patient's ability to metabolize or excrete the study drugs (e.g. chronic kidney failure with patient on dialysis) or other medical condition that in the investigator's opinion would render the patient unsuitable for this research study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Subjects receive intrathecal injection of saline at time of spinal anesthesia | Drug: Placebo<br>* Subjects receive intrathecal, preservative-free normal saline pre-operatively in conjunction with post-operative PCA morphine<br>* Other names: Preservative-free normal saline;|
| Experimental: Morphine<br>Subjects receive intrathecal injection of morphine sulfate 0.2mg at time of spinal anesthesia | Drug: Morphine<br>* Subjects receive intrathecal morphine pre-operatively to determine its level of efficacy in acute pain control post-operatively when used in conjunction with post-operative PCA morphine<br>* Other names: Preservative-free morphine sulfate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute pain at rest | Numerical rating scale pain scores were collected every 4 hours | 0-24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total opioids dispensed | Total dosage of opioids (in morphine equivalent doses) measured over 24 hours | 0-24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Morphine, TKA, Pain, TKR, Arthroplasty