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

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)

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.

Study Overview

• Status: Unknown
• Conditions: Acute Pain
• Intervention / Treatment: Drug: Placebo; Drug: Morphine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Subjects receive intrathecal injection of saline at time of spinal anesthesia	Drug: Placebo; Subjects receive intrathecal, preservative-free normal saline pre-operatively in conjunction with post-operative PCA morphine; Other Names: Preservative-free normal saline
Experimental: Morphine; Subjects receive intrathecal injection of morphine sulfate 0.2mg at time of spinal anesthesia	Drug: Morphine; 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; Other Names: Preservative-free morphine sulfate

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Stony Brook University
• Investigators: Principal Investigator: Syed Azim, MD, Stony Brook Medicine, Department of Anesthesia

Publications and helpful links

General Publications

• Kaczocha M, Azim S, Nicholson J, Rebecchi MJ, Lu Y, Feng T, Romeiser JL, Reinsel R, Rizwan S, Shodhan S, Volkow ND, Benveniste H. Intrathecal morphine administration reduces postoperative pain and peripheral endocannabinoid levels in total knee arthroplasty patients: a randomized clinical trial. BMC Anesthesiol. 2018 Feb 27;18(1):27. doi: 10.1186/s12871-018-0489-5.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): February 1, 2014
• Study Completion (Anticipated): January 1, 2017

Study Registration Dates

• First Submitted: December 1, 2015
• First Submitted That Met QC Criteria: December 1, 2015
• First Posted (Estimate): December 3, 2015

Study Record Updates

• Last Update Posted (Estimate): December 3, 2015
• Last Update Submitted That Met QC Criteria: December 1, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Pain; Arthroplasty; Morphine; TKA; TKR
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute 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: 200362