Knee Osteoarthritis, Opioid Use, Pain, Postoperative
Conditions
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.
Interventions
DRUGcannabidiol
Epidiolex (cannabidiol) oral solution
OTHEROra-sweet SF
Ora-sweet SF placebo
Sponsors
Hospital for Special Surgery, New York
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Opioid Usage in First 72 Hours Postoperatively | 0-72 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
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of CBD | 0, 1, 2, 3, 4, 6 hours after medication administration | Levels of CBD in the blood. This is measured using blood draws and lab analysis. |
| Levels of Plasma Inflammatory Marker Interleukin-6 | Preoperative, 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. The outcome measure below indicates the difference between IL6 levels on postoperative day 1 and preoperative. |
| NRS Pain at Rest | Preoperatively; 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 Movement | Preoperatively; 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. |
| Brief Pain Inventory Short Form | Preoperatively; 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. |
| Incidence of Adverse Events | Postoperatively 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 |
| Opioid Related Symptom Distress Scale (ORSDS) | Morning of postoperative day (POD) 1,2,3,4,7 and at 3 months | 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. |
| Anxiety Levels | Preoperatively; 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 |
| Cumulative Inpatient Analgesic Use (Non-opioid) | POD0 - POD3 | Total non-opioid medication usage |
| Number of Participants With Opioid and Non-opioid Medication Use | POD0 - POD3 | Opioid and non-opioid medication use by count (%) |
| Opioid & Non-opioid Analgesic Consumption | At hospital discharge to POD7 | Total opioid (morphine milligram equivalents) \& non-opioid medication usage |
| Hospital Length of Stay | At hospital discharge | Length of stay measured in hours from end of surgery to hospital discharge |
| Blinding Assessment | POD4 | 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 to Reach Discharge Physical Therapy Goals | At hospital discharge | 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 Motion | preoperatively, 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 |
| Actigraphy Sleep Efficiency | POD0 - POD3 | 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. |
| Actigraphy Sleep Time | POD0 - POD3 | 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. |
| Sleep Quality | preoperatively; 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. 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAlexandra Sideris, PhD
Hospital for Special Surgery, New York
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 60.6 years STANDARD_DEVIATION 6.8 |
| ASA Status ASA Status 1 | 1 Participants |
| ASA Status ASA Status 2 | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Height | 169.4 centimeters STANDARD_DEVIATION 12 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 11 Participants |
| Weight | 89.9 kilograms STANDARD_DEVIATION 22.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 4 / 12 | 3 / 12 | 5 / 12 |
| serious Total, serious adverse events | 1 / 12 | 0 / 12 | 1 / 12 |
Outcome results
None listed