Clinical trial NCT04749628: Cannabidiol for Bilateral Total Knee Arthroplasty
Official title: Effects of Cannabidiol (CBD) Oral Solution in Patients Undergoing Bilateral Total Knee Arthroplasty: a Randomized, Controlled, Parallel, Triple Blind, Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pain, Postoperative
Opioid Use
Knee Osteoarthritis
Lead sponsor: Hospital for Special Surgery, New York
Sponsor class: OTHER
First posted: 2021-02-11
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Cumulative Opioid Usage in First 72 hours Postoperatively
timeFrame: 0-72 hours postoperatively
Secondary outcomes:
measure: Pharmacokinetics of CBD
timeFrame: 0, 1, 2, 3, 4, 6 hours after medication administration
measure: Levels of Plasma Inflammatory Marker Interleukin-6
timeFrame: Preoperative, Postoperative day 1
measure: NRS Pain at rest
timeFrame: Preoperatively; postoperatively in the PACU, morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
measure: NRS Pain with movement
timeFrame: Preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
measure: Brief Pain Inventory Short Form
timeFrame: Preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
measure: Incidence of adverse events
timeFrame: Postoperatively in the PACU; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
measure: Opioid related Symptom Distress Scale (ORSDS)
timeFrame: Morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
measure: Anxiety levels
timeFrame: Preoperatively; Morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
measure: Cumulative inpatient analgesic use (non-opioid)
timeFrame: POD0 - POD3
measure: Opioid & non-opioid analgesic consumption
timeFrame: At hospital discharge to POD7 and at 3 months
measure: Hospital length of stay
timeFrame: End of surgery to hospital discharge
measure: Blinding Assessment
timeFrame: POD4
measure: Time to reach discharge physical therapy goals
timeFrame: At hospital discharge - up to 3 days after surgery
measure: Range of motion
timeFrame: preoperatively, 6 weeks postoperatively.
measure: Sleep quality and duration
timeFrame: POD0 - POD3
measure: Sleep quality
timeFrame: preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
Study officials:
affiliation: Hospital for Special Surgery, New York
name: Alexandra Sideris, PhD
role: PRINCIPAL_INVESTIGATOR
References: