COPE: Cannabinoids to Obviate Pain Experiment After Knee Replacement

NCT03675971 | Unknown Phase 2 DMC

• 1 other identifier: RCT19-366965
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

Total knee replacement is a major and painful orthopaedic (joint and bone) surgery where the knee joint is replaced with an artificial joint. It is an effective and successful procedure to treat severe knee arthritis and reduce pain, but many patients report intense pain after the surgery. Postoperative pain control is predominated by opioids (morphine-based drugs). While opioids are effective to manage the pain, they can have acute and chronic complications, including confusion, nausea, vomiting, constipation and high risk of addiction. Medical cannabis is an effective and safe alternative for pain treatment. Recent studies showed that patients have reported a reduction in opioid usage when taking cannabis as a substitute for pain relief. This study aims to investigate whether adding medical cannabis (cannabidiol - CBD) treatment will decrease the amount of opiates needed in the first 2 weeks after knee replacement compared to a group given placebo.

Conditions

Arthroplasty, Replacement, Knee

Keywords

Pain Management; Analgesics, Opioid; Cannabis

Outcome Measures

Primary Outcomes (1)

• Opioid consumption

  Assess cumulative opioid consumption (morphine equivalent dose) by means of drug reconciliation (medication diaries and pill counts) i.e. patients will self report how many opioid pills they took each day, by means of the medication diaries and at 4 weeks follow up will bring the pills back to clinic appointment.

  2 weeks after total knee replacement

Secondary Outcomes (6)

• Visual Analog Pain Scale

  Pain scale will be assessed at 24 hours, 2, 6 and 12 weeks after knee replacement

• Oxford knee score

  Questionnaire will be completed by patients at 6 weeks after knee replacement

• Health status and quality of life

  Questionnaire will be completed by patients at 6 weeks after knee replacement

• Quality of recovery - 15 (QoR-15)

  Questionnaire will be completed by patients at 12 weeks after knee replacement

• Self-reported opioid use and urinalysis

  The test will be completed at 12 weeks after knee replacement

Study Arms (2)

Medical Cannabis

EXPERIMENTAL

Drug: Cannabidiol

Drug: Cannabinol

Placebo

PLACEBO COMPARATOR

Placebo comparator

Drug: Placebo oral capsule

Interventions

Cannabinol DRUG

Postoperative pain treatment

Also known as: medical cannabis

Medical Cannabis

Placebo oral capsule DRUG

Placebo comparator

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age and older
• Men and women
• Patients with radiographic confirmation and clinical correlation for severe osteoarthritis diagnosis with an indication for total knee replacement
• Patients undergoing primary unilateral total knee replacement
• Patient is able to provide informed consent to participation in the study

You may not qualify if:

• Pregnancy
• Breastfeeding
• Current opioid use
• Cognitive impairment or mental illness (e.g., dementia, Alzheimer disease and psychoses), which will prevent patients from reliably providing primary outcome data
• Unable to swallow an oral tablet (medication)
• History of opiate, narcotic and alcohol abuse
• Revision total knee replacement surgery
• High risk of falls as determined by the treating physician
• Patients refusing participation
• Pre-existing/ regular cannabis use

Sponsors & Collaborators

• Unity Health Toronto: lead

Study Sites (1)

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Related Publications (15)

• Canadian Institute for Health Information. Hip and Knee Replacements in Canada, 2016-2017: Canadian Joint Replacement Registry Annual Report. Ottawa, ON: CIHI; 2018

  BACKGROUND

• Terkawi AS, Mavridis D, Sessler DI, Nunemaker MS, Doais KS, Terkawi RS, Terkawi YS, Petropoulou M, Nemergut EC. Pain Management Modalities after Total Knee Arthroplasty: A Network Meta-analysis of 170 Randomized Controlled Trials. Anesthesiology. 2017 May;126(5):923-937. doi: 10.1097/ALN.0000000000001607.

  PMID: 28288050 BACKGROUND

• Canata GL, Casale V, Chiey A. Pain management in total knee arthroplasty: efficacy of a multimodal opiate-free protocol. Joints. 2017 Feb 7;4(4):222-227. doi: 10.11138/jts/2016.4.4.222. eCollection 2016 Oct-Dec.

  PMID: 28217658 BACKGROUND

• Mohamadi A, Chan JJ, Lian J, Wright CL, Marin AM, Rodriguez EK, von Keudell A, Nazarian A. Risk Factors and Pooled Rate of Prolonged Opioid Use Following Trauma or Surgery: A Systematic Review and Meta-(Regression) Analysis. J Bone Joint Surg Am. 2018 Aug 1;100(15):1332-1340. doi: 10.2106/JBJS.17.01239.

  PMID: 30063596 BACKGROUND

• Hadlandsmyth K, Vander Weg MW, McCoy KD, Mosher HJ, Vaughan-Sarrazin MS, Lund BC. Risk for Prolonged Opioid Use Following Total Knee Arthroplasty in Veterans. J Arthroplasty. 2018 Jan;33(1):119-123. doi: 10.1016/j.arth.2017.08.022. Epub 2017 Aug 24.

  PMID: 28927564 BACKGROUND

• Morris BJ, Mir HR. The opioid epidemic: impact on orthopaedic surgery. J Am Acad Orthop Surg. 2015 May;23(5):267-71. doi: 10.5435/JAAOS-D-14-00163.

  PMID: 25911660 BACKGROUND

• Goesling J, Moser SE, Zaidi B, Hassett AL, Hilliard P, Hallstrom B, Clauw DJ, Brummett CM. Trends and predictors of opioid use after total knee and total hip arthroplasty. Pain. 2016 Jun;157(6):1259-1265. doi: 10.1097/j.pain.0000000000000516.

  PMID: 26871536 BACKGROUND

• Franklin PD, Karbassi JA, Li W, Yang W, Ayers DC. Reduction in narcotic use after primary total knee arthroplasty and association with patient pain relief and satisfaction. J Arthroplasty. 2010 Sep;25(6 Suppl):12-6. doi: 10.1016/j.arth.2010.05.003. Epub 2010 Jun 26.

  PMID: 20580191 BACKGROUND

• Soffin EM, Waldman SA, Stack RJ, Liguori GA. An Evidence-Based Approach to the Prescription Opioid Epidemic in Orthopedic Surgery. Anesth Analg. 2017 Nov;125(5):1704-1713. doi: 10.1213/ANE.0000000000002433.

  PMID: 29049115 BACKGROUND

• Cozowicz C, Olson A, Poeran J, Morwald EE, Zubizarreta N, Girardi FP, Hughes AP, Mazumdar M, Memtsoudis SG. Opioid prescription levels and postoperative outcomes in orthopedic surgery. Pain. 2017 Dec;158(12):2422-2430. doi: 10.1097/j.pain.0000000000001047.

  PMID: 28891865 BACKGROUND

• Lynch ME, Campbell F. Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials. Br J Clin Pharmacol. 2011 Nov;72(5):735-44. doi: 10.1111/j.1365-2125.2011.03970.x.

  PMID: 21426373 BACKGROUND

• Schrot RJ, Hubbard JR. Cannabinoids: Medical implications. Ann Med. 2016;48(3):128-41. doi: 10.3109/07853890.2016.1145794. Epub 2016 Feb 25.

  PMID: 26912385 BACKGROUND

• Manzanares J, Julian M, Carrascosa A. Role of the cannabinoid system in pain control and therapeutic implications for the management of acute and chronic pain episodes. Curr Neuropharmacol. 2006 Jul;4(3):239-57. doi: 10.2174/157015906778019527.

  PMID: 18615144 BACKGROUND

• Vigil JM, Stith SS, Adams IM, Reeve AP. Associations between medical cannabis and prescription opioid use in chronic pain patients: A preliminary cohort study. PLoS One. 2017 Nov 16;12(11):e0187795. doi: 10.1371/journal.pone.0187795. eCollection 2017.

  PMID: 29145417 BACKGROUND

• Lucas P, Walsh Z. Medical cannabis access, use, and substitution for prescription opioids and other substances: A survey of authorized medical cannabis patients. Int J Drug Policy. 2017 Apr;42:30-35. doi: 10.1016/j.drugpo.2017.01.011. Epub 2017 Feb 9.

  PMID: 28189912 BACKGROUND

MeSH Terms

Conditions

Agnosia; Marijuana Abuse

Interventions

Cannabinol; Medical Marijuana

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals; Pharmaceutical Preparations

Study Officials

• Amit Atrey, MD

  Unity Health Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luana Melo, PhD

CONTACT

416-864-6060; melol@smh.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel Assignment

Study Record Dates

• First Submitted: August 28, 2018
• First Posted: September 18, 2018
• Study Start: May 1, 2020
• Primary Completion: May 15, 2021
• Study Completion: May 1, 2022
• Last Updated: October 1, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)