Dronabinol in Total Knee Arthroplasty (TKA)

Effects of Perioperative Dronabinol Use in Total Knee Arthroplasty

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:

1. 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?
2. Is there an effect of perioperative dronabinol use in the total knee arthroplasty patient on POD2 pain scores with ambulation?
3. Will hospital length of stay following total knee arthroplasty be affected in patients who use perioperative dronabinol as compared to control?
4. Does the use of perioperative dronabinol affect time to reach physical therapy discharge goals in postoperative total knee arthroplasty patients?
5. 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 affects postoperative opioid consumption 24-48 hours following their total knee arthroplasty surgery.

Study Overview

• Status: Completed
• Conditions: Total Knee Arthroplasty; Opioid Use
• Intervention / Treatment: Drug: Dronabinol 5mg Cap; Other: Placebo oral tablet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Hospital For Special Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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
• Sleep Apnea

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dronabinol; 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; Dronabinol is a synthetic tetrahydrocannabinol (THC) agent approved for nausea and vomiting with chemotherapy and as an appetite stimulant in AIDS patients.; Other Names: marinol
Placebo Comparator: Placebo; 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; Non-active placebo; Other Names: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Opioid Consumption 24-48 Hours Post-operatively	The primary outcome of the study will be cumulative patient opioid consumption 24-48 hours post operatively, defined by total morphine equivalents (MEs). This outcome will be measured starting at recovery room entry and conclude at 48 hours after anesthesia stop time.	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
Average Pain Score With Ambulation Reported on a Numeric Rating Scale (NRS)	Patient pain with ambulation on postoperative day (POD) 1, 2, 7, 90 and 180, defined by patient reported Numeric Rating Scale (NRS) pain score, (from 0-no pain to 10-worst pain imaginable).	Post operative day 1, 2, 7, 90 and 180
Average Pain Score at Rest Reported on a Numeric Rating Scale (NRS)	Patient pain at rest upon PACU entry and in the morning of postoperative day (POD)1, POD2, POD7, POD90 and POD180 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), POD 1, 2, 7, 90 and 180
Pain With Physical Therapy	Patient pain during morning physical therapy on postoperative day (POD)1 and 2, defined by patient reported Numeric Rating Scale (NRS) pain score, (from 0-no pain to 10-worst pain imaginable).	Postoperative Day 1 and Postoperative Day 2
Length of Hospital Stay (Hours)	Hospital length of stay from procedure start time to time of discharge	Post operative day 0 (beginning in the PACU)-Discharge
the Number of Desaturation Events	Postoperative desaturation events are defined as the number of times oxygen saturation dropped below 88% for at least 20 seconds or more. The number of such events will be counted per subject during the monitoring period, beginning in the immediate postoperative period on postoperative day (POD)0 (in the PACU) and will continue until the end post operative day 2/patient discharge, whichever occurs first. 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
PainOUT Scale Questions	PainOut assesses post-surgical pain by collecting data on pain intensity, interference with daily activities, and other related factors. Questionnaire uses multiple scales from 0 (none/not at all/did not interfere/extremely dissatisfied) to 10 (extreme/severe/worst pain imaginable/completely interfered/extremely satisfied). Pain severity/Interference/Symptom questions are scored from 0-10, with higher scores indicating worse outcomes. With a scale of 0-10, higher scores indicate better outcomes for the following questions: decision participation question and satisfaction question. The following questions used a scale of 1-11, where 1=0% and 11=100%: Pain relief (a higher percentage indicates better outcome) Time with severe pain (a higher percentage indicates worse outcome)	24 hours post operative discharge, 48 hours post operative discharge, 7 days post operative discharge, 90 days post operative discharge, 180 days post operative discharge
PainOut Count Questions	The following questions used a scale of Yes/No, reporting number of patients with Yes; Been out of bed since surgery; Would have liked more pain treatment; Received information about pain treatment; Used non-medicine methods to relieve pain; Persistent painful condition for 3 months or more	24 hours post operative discharge, 48 hours post operative discharge, 7 days post operative discharge, 90 days post operative discharge, 180 days post operative discharge
DN4 Score	DN4 questionnaire to assess neuropathic pain on postoperative day (POD)1, 2, 7, 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 (burning, painful cold, electric shocks, tingling, pins and needles, numbness, itching, hypoesthesia to touch, hypoesthesia to pinprick, pain increased by brushing). Total score is calculated by summing the total of the individual question scores, for a total score range of 0-10, with a score of greater than or equal to 4 indicating the patient may be suffering from neuropathic pain.	24 hours post operative discharge, 48 hours post operative discharge, 7days post operative discharge, 3 months post operative discharge, 6 months post operative discharge
Opioid-Related Symptom Distress (ORSDS) Scale	The Opioid-Related Symptom Distress Scale (ORSDS) is a scale that assesses three dimensions of symptom distress (frequency, severity, and bothersomeness) for 12 symptoms. The symptom-specific ORSDS is calculated by taking the average of the three symptom distress dimensions. The composite score will be reported for postoperative day (POD)1 and POD2. If a patient denies experiencing a particular symptom, their response will be coded as 0. If they do: Frequency will be assessed using a 4 point scale: rarely; occasionally; frequently; almost constantly with 1 being the lowest and 4 being the highest. Severity is assessed using a 4 point scale: slight; moderate; severe; very severe with 1 being the lowest and 4 being the highest. Bothersomeness is assessed using a 5 point scale: not at all; a little bit; somewhat; quite a bit; very much with 1 being the lowest and 5 being the highest.	24 hours post operative discharge, 48 hours post operative discharge
Non-opioid Analgesic Consumption	Patient consumption of non-opioid analgesics in the post-anesthesia care unit (PACU) and on postoperative day (POD)1, POD2, POD7. This was measured for acetaminophen, ibuprofen, ketorolac, meloxicam, naproxen, and gabapentin as yes/no. Number of participants who report "yes" for each non-opioid analgesic is reported.	PACU, POD1, POD2, POD7
Sleep Disturbance: Total Sleep Time	Sleep disturbance via actigraphy measurement using the ActiGraph wGT3X-BT activity monitor. Measured during the first 24 hours postoperatively.	Post operative day 0 (beginning in the PACU)- 24 hours post operative
Sleep Disturbance: Wake After Sleep Onset	Sleep disturbance via actigraphy measurement using the ActiGraph wGT3X-BT activity monitor. Wake After Sleep Onset is the duration of time a patient was awake after falling asleep and before getting out of bed. Measured during the first 24 hours postoperatively.	Post operative day 0 (beginning in the PACU)- 24 hours post operative
Sleep Disturbance: Sleep Efficiency	Sleep disturbance via actigraphy measurement using the ActiGraph wGT3X-BT activity monitor. Sleep Efficiency is the ratio between total sleep time and the total time in bed. Measured during the first 24 hours postoperatively. Sleep Efficiency ratio is expressed as a percentage, where higher values represent better outcomes.	Post operative day 0 (beginning in the PACU)- 24 hours post operative
Sleep Disturbance: Number of Awakenings	Sleep disturbance via actigraphy measurement using the ActiGraph wGT3X-BT activity monitor. Measured as number of awakenings during the first 24 hours postoperatively.	Post operative day 0 (beginning in the PACU)- 24 hours post operative
Cognitive Assessment	Measured as yes/no for a series of 13 questions asking patients if they have experienced any: change of mood, difficulty with memory, slurring of speech, blurred vision, hallucinations, increased awareness of surroundings, palpitations, headache, dizziness, drowsiness, dry mouth, involuntary muscle twitching, or tremors. Number of participants who report "yes" for each symptom is reported. Measured in the post-anesthesia care unit (PACU), between PACU exist and midnight (Post-op), postoperative day (POD)1, POD2	PACU, Post-Op, POD1, POD2
Opioid Consumption in the Post-anesthesia Care Unit and Postoperative Day 1	Opioid consumption measured in morphine milligram equivalents in the post-anesthesia care unit and postoperative day 1 (analyzed as 0-24 hours after surgery)	post-anesthesia care unit and postoperative day 1
Opioid Consumption at Postoperative Day 90	Number of participants reporting opioid use at postoperative day 90.	Postoperative Day 90

Collaborators and Investigators

• Sponsor: Hospital for Special Surgery, New York
• Investigators: Principal Investigator: Kethy Jules-Elysee, M.D., Hospital for Special Surgery, New York

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2021
• Primary Completion (Actual): October 6, 2023
• Study Completion (Actual): April 1, 2024

Study Registration Dates

• First Submitted: January 19, 2021
• First Submitted That Met QC Criteria: January 27, 2021
• First Posted (Actual): February 2, 2021

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Opioid; Knee Arthroplasty; Dronabinol
• Additional Relevant MeSH Terms: Organic Chemicals; Pharmaceutical Preparations; Dosage Forms; Hydrocarbons; Terpenes; Cannabinoids; Dronabinol; Capsules
• Other Study ID Numbers: 2019-1416

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article after de-identification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: Investigators whose proposed use of the data has been approved by an Independent review committee ("learned intermediary") identified for this purpose and who have signed a DUA.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes