Dronabinol in Total Knee Arthroplasty (TKA)

Study Overview
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Brief Summary
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The goal of this double-blinded randomized controlled trial is to compare whether the addition of Dronabinol compared to a placebo will affect opioid intake in patients undergoing a total knee arthroplasty. The main question it aims to answer are: Does perioperative dronabinol use (starting in the immediate preoperative period (enrollment before 1 PM), with BID dosing concluding the evening of POD2) affect postoperative opioid consumption 24-48 hours following total knee arthroplasty? Is there an effect of perioperative dronabinol use in the total knee arthroplasty patient on POD2 pain scores with ambulation? Will hospital length of stay following total knee arthroplasty be affected in patients who use perioperative dronabinol as compared to control? Does the use of perioperative dronabinol affect time to reach physical therapy discharge goals in postoperative total knee arthroplasty patients? Is there a change in number of postoperative oxygen desaturation events in patients following total knee arthroplasty based on perioperative dronabinol use? Participants will: Be randomized to take the dronabinol or placebo medication in 5 dosage Answer survey questions in regard to pain, postop nausea/vomiting, cognitive/adverse event, and outcome quality and support of decision making. Be connected to a Masimo to record oxygen saturation and an Actigraph to record sleep quality. Researchers will compare two groups: 1) intervention group and 2) control group to see if dronabinol affect postoperative opioid consumption 24-48 hours following their total knee arthroplasty surgery.

Detailed Description
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The objective of this study is to examine the possible therapeutic advantages of administering perioperative dronabinol to individuals who are undergoing unilateral total knee arthroplasty (TKA). With the utilization of contemporary regional anesthetic procedures and peripheral nerve blocks, pain management is typically effective in the immediate aftermath of total knee arthroplasty (TKA) within the first day after surgery. Rebound pain is shown to occur on the second day following postoperative discharge (POD2), once the analgesic blocks administered during the procedure have ceased to be effective. Previous studies have suggested that dronabinol, a synthetic form of THC, may have potential analgesic properties. Our goal is to find out if giving dronabinol before surgery could lower the number of opioids that people need on postoperative day 2 (POD2) in people who are having total knee arthroplasty (TKA). This research could provide valuable insights into alternative pain management strategies for TKA patients, potentially minimizing opioid-related side effects and improving overall patient outcomes.

Official Title
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Effects of Perioperative Dronabinol Use in Total Knee Arthroplasty

Conditions
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Total Knee Arthroplasty, Opioid Use

Intervention / Treatment
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* Drug: Dronabinol 5mg Cap
* Other: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged between 18-70 years old with osteoarthrosis scheduled for primary unilateral knee arthroplasty with a participating surgeon Planned use of regional anesthetic technique during surgery involving infiltration between the popliteal artery and the capsule of the posterior knee (IPACK), adductor canal block (ACB) and periarticular injection (PAI) Ability to follow study protocol Exclusion Criteria: Patients less than 18 years of age or older than 70 years of age Contraindication to regional or neuraxial anesthetic Intended use of general anesthesia Revision surgery Chronic opioid use (for >3 months prior to surgery) Cannabis/cannabinoid use within the last 3 months ASA class of IV or greater Active or history of major mental history (as defined by the Diagnostic and Statistical Manual of Mental Disorders-5 [DSM-5]; i.e. major depressive disorder, anxiety, bipolar disorder, schizophrenia) History of seizures Use of antidepressants Use of anticonvulsants Use of Coumadin Use of Disulfuram Use of Metronidazole Non-English speakers BMI ≥40

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dronabinol<br>57 subjects undergoing primary Total Knee Arthroplasty will be randomized to receive BID (2x/day) dosing of 5 mg of Dronabinol beginning on the day of surgery and with the final dose on the morning of POD (postoperative day) 2. | Drug: Dronabinol 5mg Cap<br>* Dronabinol is a synthetic tetrahydrocannabinol (THC) agent approved for nausea and vomiting with chemotherapy and as an appetite stimulant in AIDS patients.<br>* Other names: marinol;|
| Placebo Comparator: Placebo<br>57 subjects undergoing primary Total Knee Arthroplasty will be randomized to receive BID (2x/day) dosing of a non-active placebo pill beginning on the day of surgery and with the final dose on the morning of POD (postoperative day) 2. | Other: Placebo oral tablet<br>* Non-active placebo<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid Consumption 24-48 hours post-operatively | The primary outcome of the study will be patient opioid consumption 24-48 hours post operatively, defined by total morphine equivalents (MEs). This outcome will be measured throughout the patient hospitalization and conclude at the time of discharge. | 24-48 hours post-operatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to reach discharge from physical therapy | Time to reach discharge physical therapy goals, as defined by the number of hours required to meet the following criteria: stable vital signs during Physical therapy (PT), safe independent transfer from bed to standing as well as transfer in and out of seated position, ability to walk 40 feet only with aid of crutch or walker. This outcome will be measured prior to patient discharge. | Post operative day 0 (beginning in the PACU)-Discharge, assessed up to 7 days | 
| Patient pain score with ambulation reported on a numeric rating scale (NRS) | Patient pain with ambulation on POD2, defined by patient reported Numeric Rating Scale (NRS) pain score, (from 0-no pain to 10-worst pain imaginable). | Post operative day 2, 48 hours post operative discharge | 
| Patient pain score at rest reported on a numeric rating scale (NRS) | Patient pain at rest upon PACU entry and in the morning of POD1, POD2 and POD7 and POD90 defined by patient reported Numeric Rating Scale (NRS) pain score, (from 0-no pain to 10-worst pain imaginable). | Post operative day 0 (beginning in the PACU), 24 hours post operation discharge, 48 hours post operation discharge, 7 days post operation discharge, and 90 days post operation discharge | 
| Pain with physical therapy | Patient pain during morning physical therapy on POD1 and 2, defined by patient reported Numeric Rating Scale (NRS) pain score, (from 0-no pain to 10-worst pain imaginable). | 24 hours post operation discharge - 48 hours post operation discharged | 
| Opioid consumption | Patient opioid consumption post-operatively, measured in morphine equivalents | 24 hours post operative discharge- 48 hours post operative discharge | 
| Length of stay (hours) | Hospital length of stay from day of surgery to discharge | Post operative day 0 (beginning in the PACU)-Discharge, assessed up to 7 days | 
| Percentage of time and total time of desaturation events | Postoperative oxygen desaturation events will be reported in minutes. This outcome will be measured beginning in the immediate postoperative period on POD0 (in the PACU) and will continue until the end post operative day 2. Oxygen desaturation is defined when measured SpO2 is less than 88%. Measurements will only be recorded if the desaturation event happens for 20 seconds or longer. | Post operative day 0 (beginning in the PACU)-48 hours post operative discharge | 
| Cognitive assessment | Cognitive assessment via confusion assessment method (CAM) in PACU, on POD1, 2, and 7 | Post operative day 0 (beginning in the PACU), 24 hours post operative discharge, 48 hours post operative discharge, 7 days post operative discharge | 
| painOUT score | painOUT questionnaire to assess pain levels/types on POD1, 2, 90 and 180. Questionnaire uses multiple scales from 0 (none/not at all) to 10 (extreme/severe), percentages 0-100% for amount of pain relief, and yes or no questions. Higher scores will mean worse outcomes except for pain relief questions which are focused around how much pain relief they felt. | 24 hours post operative discharge, 48 hours post operative discharge, 7 days post operative discharge, 3 months post operative discharge, 6 months post operative discharge | 
| DN4 score | DN4 questionnaire to assess neuropathic pain on POD1, 2, 90 and 180. The DN4 questionnaire is a series of Yes or No questions that revolves around the characteristics that may suggest the presence or development of neuropathic conditions/pain. | 24 hours post operative discharge, 48 hours post operative discharge, 3 months post operative discharge, 6 months post operative discharge | 
| Opioid-Related Symptom Distress (ORSDS) Scale | ORSDS questionnaire to assess opioid-related side effects on POD1 and 2. The questionnaire has multiple Yes or No questions, as well as a wording scale from no side effect to almost consistently. Better outcomes will be constant with no side effect reported. | 24 hours post operative discharge, 48 hours post operative discharge | 
| Non-opioid analgesic consumption | Patient consumption of non-opioid analgesics from PACU entry through POD7 | 24 hours post operative discharge, 48 hours post operative discharge, 7 days post operative discharge | 
| Opioid use and patient pain (reported on a numeric scale) at POD90 | Opioid use will be calculated and reported as representative morphine units, and pain (via NRS pain scale) at POD90 will be collected. The NRS pain scale is a questionnaire that uses 0-no pain to 10- worst pain imaginable as the rubric. e months post operative discharge is viewed as the onset of chronic pain. lower scores will be deemed as better outcomes. | 3 months post operative discharge | 
| Sleep disturbance | Sleep disturbance via acitgraphy measurement using the ActiGraph wGT3X-BT activity monitor | Post operative day 0 (beginning in the PACU)- 48 hours post operative discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Knee Arthroplasty, Dronabinol, Opioid