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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
37
Epidiolex (cannabidiol) oral solution
Ora-sweet SF placebo
Hospital for Special Surgery
New York, New York, United States
Cumulative Opioid Usage in First 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
Time frame: 0-72 hours postoperatively
Pharmacokinetics of CBD
Levels of CBD in the blood. This is measured using blood draws and lab analysis.
Time frame: 0, 1, 2, 3, 4, 6 hours after medication administration
Levels of Plasma Inflammatory Marker Interleukin-6
Interleukin-6 (IL6) is an inflammatory marker found in plasma. The levels of IL6 are measured using blood draws and lab analysis. The outcome measure below indicates the difference between IL6 levels on postoperative day 1 and preoperative.
Time frame: Preoperative, Postoperative day 1
NRS Pain at Rest
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.
Time frame: Preoperatively; postoperatively in the PACU, morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
NRS Pain With Movement
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.
Time frame: Preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Brief Pain Inventory Short Form
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.
Time frame: Preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Incidence of Adverse Events
Adverse events, including allergic reactions, pyrexia (fever), somnolence (excessive sleepiness), GI problems (upset stomach, diarrhea), dry mouth, escalation of post-operative opioid requirement
Time frame: Postoperatively in the PACU; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Opioid Related Symptom Distress Scale (ORSDS)
Opioid related Symptom Distress Scale (ORSDS) measures opioid related side effects. There are 12 side effects with 3 subcategories (severity, frequency, bothersomeness) each with 5 different responses (scored 0-4 with higher scores indicating worse symptoms). The ORSDS composite score was calculated by averaging the scores for each symptom.
Time frame: Morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Anxiety Levels
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
Time frame: Preoperatively; Morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Cumulative Inpatient Analgesic Use (Non-opioid)
Total non-opioid medication usage
Time frame: POD0 - POD3
Number of Participants With Opioid and Non-opioid Medication Use
Opioid and non-opioid medication use by count (%)
Time frame: POD0 - POD3
Opioid & Non-opioid Analgesic Consumption
Total opioid (morphine milligram equivalents) \& non-opioid medication usage
Time frame: At hospital discharge to POD7
Number of Participants With Opioid and Non-opioid Medication Use
Opioid \& non-opioid medication use by count (%)
Time frame: POD0 to POD7 and 3 months
Hospital Length of Stay
Length of stay measured in hours from end of surgery to hospital discharge
Time frame: At hospital discharge
Blinding Assessment
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. The index (number) is calculated as a group-level summary statistic, computed from the distribution of guesses across all participants in a group.
Time frame: POD4
Time to Reach Discharge Physical Therapy Goals
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
Time frame: At hospital discharge
Range of Motion
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
Time frame: preoperatively, 6 weeks postoperatively.
Actigraphy Sleep Efficiency
Sleep quality assessed by actigraphy using ActiGraph wGT3X-BT activity monitor. Higher sleep efficiency indicates better sleep quality. Sleep efficiency was calculated between the hours of 11pm and 6am each night.
Time frame: POD0 - POD3
Actigraphy Sleep Time
Sleep quality assessed by actigraphy using ActiGraph wGT3X-BT activity monitor. Higher sleep time indicates better sleep quality. Total sleep time was calculated between the hours of 11pm and 6am each night.
Time frame: POD0 - POD3
Sleep Quality
Sleep quality assessed by Leeds sleep evaluation questionnaire (LSEQ). Responses to 10 questions will be measured on a slider scale ranging from 0-100. Higher scores indicate better outcomes. Getting to Sleep domain scores were calculated by averaging the responses to Questions 1-3 regarding falling asleep. Quality of Sleep domain scores were calculated by averaging the responses to Questions 4-5 regarding quality of sleep. Awake Following Sleep domain scores were calculated by averaging the responses to Questions 6-7 regarding awakening from sleep. Behaviour Following Wakening domain scores were calculated by averaging the responses to Questions 8-10 regarding feeling, balance, and coordination upon awakening.
Time frame: preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
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