MedPath

Cannabidiol for Bilateral Total Knee Arthroplasty

Phase 4
Completed
Conditions
Pain, Postoperative
Opioid Use
Knee Osteoarthritis
Interventions
Other: Ora-sweet SF
Registration Number
NCT04749628
Lead Sponsor
Hospital for Special Surgery, New York
Brief Summary

In light of the opioid epidemic and evidence suggesting that cannabis may be opioid-sparing, we are in a unique position to conduct a novel, high-impact study that would set the stage for future RCTs examining the effects of a nonintoxicating and nonaddictive cannabinoid in an orthopedic patient population. Epidiolex®, an oral cannabidiol (CBD) solution, is the first ever cannabis-derived medication to be approved by the Food \& Drug Administration. Our aim is to conduct a pilot study using a placebo oral solution, 400mg and 800mg Epidiolex® to gather data on its effects on patients undergoing bilateral total knee arthroplasty (BTKA). We will be estimating whether Epidiolex® is associated with minimal opioid use and adequate analgesia. We will also assess its tolerability, pharmacokinetics, and effects on inflammatory markers in the perioperative setting.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
37
Inclusion Criteria
  • Age 18 to 75
  • Scheduled for same-day bilateral total knee replacements with participating surgeons
  • American Society of Anesthesiologists (ASA) Physical Status 1 or 2
Exclusion Criteria
  • ASA 3 and higher
  • Weight < 40kg
  • Planned use of general anesthesia
  • Contraindication to major components of study protocol
  • Cannabis or cannabinoid use within the past 3 months (recreational and/or medical)
  • Use or ingestion of hemp seeds or hemp oil in any form within the past 30 days
  • Chronic opioid use (>3 months)
  • Coumadin use
  • Current use of SSRI or SNRIs
  • History of substance abuse or dependence
  • Active or history of major psychiatric illness
  • Severe cardiovascular disorder
  • Severe hepatic or renal insufficiency (transaminase levels above ULN)
  • History of epilepsy
  • Diagnosis of rheumatic disease, autoimmune disease, or immunodeficiency (e.g. rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, multiple sclerosis, etc.)
  • Use of valproate or clobazam
  • Known or suspected hypersensitivity, allergy, or contraindication to cannabinoids or any of the excipients in the study medications (i.e. sesame oil, sucralose, strawberry flavor)
  • Active use of steroids - oral steroids upon admission
  • Stress dose steroids
  • Non-English speakers
  • Planned discharge to home without caregiver(s)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Ora-sweet SFOra-sweet SF-
400mg cannabidiolcannabidiol-
800mg cannabidiolcannabidiol-
Primary Outcome Measures
NameTimeMethod
Cumulative Opioid Usage in First 72 hours Postoperatively0-72 hours postoperatively

Cumulative opioid usage over the first 72 hours after surgery. Measured in morphine equivalents (ME), a scale that measure opioid usage among all opioid medications

Secondary Outcome Measures
NameTimeMethod
Pharmacokinetics of CBD0, 1, 2, 3, 4, 6 hours after medication administration

Levels of CBD in the blood. This is measured using blood draws and lab analysis.

Opioid related Symptom Distress Scale (ORSDS)Morning of postoperative day (POD) 1,2,3,4,7 and at 3 months

ORSDS measures opioid related side effects. There are 13 side effects with 3 subcategories (severity, frequency, bothersomeness) each with 5 different responses (scored 0-4).

Hospital length of stayEnd of surgery to hospital discharge

Length of stay measured in hours

Levels of Plasma Inflammatory Marker Interleukin-6Preoperative, Postoperative day 1

Interleukin-6 (IL6) is an inflammatory marker found in plasma. The levels of IL6 are measured using blood draws and lab analysis.

NRS Pain at restPreoperatively; postoperatively in the PACU, morning of postoperative day (POD) 1,2,3,4,7 and at 3 months

Pain at rest measured using numerical rating scale(NRS) from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

NRS Pain with movementPreoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months

Pain with movement using numerical rating scale(NRS) from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.

Incidence of adverse eventsPostoperatively in the PACU; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months

Adverse events, including allergic reactions, pyrexia (fever), somnolence (excessive sleepiness), GI problems (upset stomach, diarrhea), dry mouth, escalation of post-operative opioid requirement

Sleep qualitypreoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months

Sleep quality assessed by Leeds sleep evaluation questionnaire (LSEQ). Responses to 10 questions will be measured on a slider scale ranging from 0-100.

Opioid & non-opioid analgesic consumptionAt hospital discharge to POD7 and at 3 months

Total opioid \& non-opioid medication usage

Brief Pain Inventory Short FormPreoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months

Brief Pain inventory short form measures the severity of pain and its impact on function. It measures pain from 0-10 0 being no pain whatsoever to 10 being the worst pain imaginable. It measures impact on function from 0-10, 0 being no impact whatsoever to 10 being completely impactful.

Cumulative inpatient analgesic use (non-opioid)POD0 - POD3

Total non-opioid medication usage

Time to reach discharge physical therapy goalsAt hospital discharge - up to 3 days after surgery

Physical therapy goals for total knee replacement include walking 100 feet, going up and down 4 stairs, and independent transfer (meaning they can move from a lying to standing position independently). Patients need to complete these goals before being discharged

Range of motionpreoperatively, 6 weeks postoperatively.

Range of motion, or extension and flexion of the knees, are measured preoperatively and at the patients' 6 week surgeon visit. It is measured in degrees

Sleep quality and durationPOD0 - POD3

Sleep quality assessed by actigraphy using ActiGraph wGT3X-BT activity monitor

Anxiety levelsPreoperatively; Morning of postoperative day (POD) 1,2,3,4,7 and at 3 months

Hospital Anxiety and Depression Scale (HADS) asks 14 questions, 7 about anxiety and 7 about depression. Responses are scored from 0-3. Responses between the two categories are summed and scoring is as follows: 0-7 = normal, 8-10=borderlines abnormal, 11-21=abnormal

Blinding AssessmentPOD4

Patients are asked which treatment they think they received. The correctness of their guesses is then measured using the bang-blinding index to see if patients were able to accurately guess which treatment they received. It is measured on a scale of -1 to 1. Scores closer to 0 indicate better blinding, or patients not being able to guess their treatment

Trial Locations

Locations (1)

Hospital for Special Surgery

🇺🇸

New York, New York, United States

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