Dronabinol in Total Knee Arthroplasty (TKA)

Sponsor

Hospital for Special Surgery, New York (Other)

Overall Status

Recruiting

CT.gov ID

NCT04734080

Collaborator

(none)

110

Enrollment

Location

Arms

Anticipated Duration (Months)

3.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will investigate the potential therapeutic benefit of perioperative dronabinol use in patients undergoing unilateral total knee arthroplasty (TKA). With current advanced regional anesthetic techniques and peripheral nerve blocks, pain is generally well controlled following TKA on post operative day (POD) 1. There is a rebound pain that exists, however, on post operative discharge day 2 (POD2) when these blocks are no longer effective. We aim to study a potential reduction in opioid consumption on POD2 with perioperative dronabinol use in TKA patients

Condition or Disease	Intervention/Treatment	Phase
Total Knee Arthroplasty Opioid Use	Drug: Dronabinol 5mg Cap Drug: Placebo oral tablet	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

110 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

Throughout cannabinoid research, there has been concern about potential unblinding due to the side effect profile of this class of medication. Prior meta-analyses have advocated for the use of active placebo, with concern that unblinding may misrepresent the effects of clinical trials. However, due to evidence of histamine receptor involvement in pain transmission, as well as overlap in antihistamine antiemetic use and common cannabinoid side effect profiles, we have chosen to use non-active placebo. Our hope is to elicit maximum benefit of cannabinoid dosing perioperatively without confounding variables. With use of non-active placebo, we will perform a comprehensive blinding analysis following the study period to ensure adequate blinding.

Primary Purpose:

Treatment

Official Title:

Effects of Perioperative Dronabinol Use in Total Knee Arthroplasty

Actual Study Start Date :

Mar 1, 2021

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dronabinol 55 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.
Placebo Comparator: Placebo 55 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.	Drug: Placebo oral tablet Non-active placebo

Arm

Intervention/Treatment

Experimental: Dronabinol

55 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.

Placebo Comparator: Placebo

55 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.

Drug: Placebo oral tablet

Non-active placebo

Outcome Measures

Primary Outcome Measures

Opioid Consumption 24-48 hours post-operatively [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.

Secondary Outcome Measures

Time to reach discharge from physical therapy [Post operative day 0 (beginning in the PACU)-Discharge, assessed up to 7 days]
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.
Patient pain score with ambulation reported on a numeric rating scale (NRS) [Post operative day 2, 48 hours post operative discharge]
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).
Patient pain score at rest reported on a numeric rating scale (NRS) [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]
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).
Pain with physical therapy [24 hours post operation discharge - 48 hours post operation discharged]
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).
Opioid consumption [24 hours post operative discharge- 48 hours post operative discharge]
Patient opioid consumption post-operatively, measured in morphine equivalents
Length of stay (hours) [Post operative day 0 (beginning in the PACU)-Discharge, assessed up to 7 days]
Hospital length of stay from day of surgery to discharge
Percentage of time and total time of desaturation events [Post operative day 0 (beginning in the PACU)-48 hours post operative discharge]
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.
Cognitive assessment [Post operative day 0 (beginning in the PACU), 24 hours post operative discharge, 48 hours post operative discharge, 7 days post operative discharge]
Cognitive assessment via confusion assessment method (CAM) in PACU, on POD1, 2, and 7
painOUT score [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]
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.
DN4 score [24 hours post operative discharge, 48 hours post operative discharge, 3 months post operative discharge, 6 months post operative discharge]
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.
Opioid-Related Symptom Distress (ORSDS) Scale [24 hours post operative discharge, 48 hours post operative discharge]
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.
Non-opioid analgesic consumption [24 hours post operative discharge, 48 hours post operative discharge, 7 days post operative discharge]
Patient consumption of non-opioid analgesics from PACU entry through POD7
Opioid use and patient pain (reported on a numeric scale) at POD90 [3 months post operative discharge]
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.
Sleep disturbance [Post operative day 0 (beginning in the PACU)- 48 hours post operative discharge]
Sleep disturbance via acitgraphy measurement using the ActiGraph wGT3X-BT activity monitor

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital for Special Surgery	New York	New York	United States	10021

Sponsors and Collaborators

Hospital for Special Surgery, New York

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hospital for Special Surgery, New York

ClinicalTrials.gov Identifier:

NCT04734080

Other Study ID Numbers:

2019-1416

First Posted:

Feb 2, 2021

Last Update Posted:

Jul 15, 2022

Last Verified:

Jul 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Keywords provided by Hospital for Special Surgery, New York

Knee Arthroplasty

Dronabinol

Opioid

Additional relevant MeSH terms:

Dronabinol

Study Results

No Results Posted as of Jul 15, 2022