Dronabinol in Total Knee Arthroplasty (TKA)

Opioid Use Clinical Trial

Official title:

Effects of Perioperative Dronabinol Use in Total Knee Arthroplasty

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04734080
• Other study ID #: 2019-1416
• Status: Completed
• Phase: Phase 4
• Start date: March 1, 2021
• Est. completion date: April 1, 2024

Study information

• Verified date: April 2024
• Source: Hospital for Special Surgery, New York
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 affect postoperative opioid consumption 24-48 hours following their total knee arthroplasty surgery.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: April 1, 2024
• Est. primary completion date: October 6, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Opioid Use
• Total Knee Arthroplasty

Intervention

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:
• Placebo oral tablet
Non-active placebo

Locations

Country	Name	City	State
United States	Hospital for Special Surgery	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Hospital for Special Surgery, New York

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Opioid consumption	Patient opioid consumption post-operatively, measured in morphine equivalents	24 hours post operative discharge- 48 hours post operative discharge
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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