Cannabidiol to reduce persistent post-surgical pain following total knee arthroplasty: protocol for a multi-centre, randomized, controlled pilot trial

BACKGROUND: Total knee arthroplasty (TKA) is commonly performed to reduce pain and improve functional limitations associated with late-stage osteoarthritis. However, 1 in 4 patients experience persistent post-surgical pain (PPSP); a complaint that is associated with higher peri-operative pain. Cannabidiol (CBD) possesses analgesic and anti-inflammatory properties that may reduce the risk of persistent pain among TKA patients. We designed a pilot trial to assess the feasibility of a definitive trial comparing CBT to placebo for reducing PPSP in patients undergoing TKA. METHODS: We propose a randomized, controlled, pilot trial in which 40 patients scheduled to undergo TKA will be randomized to receive MPL-001 (an oral CBD-dominant formulation) or placebo, in addition to standard care. The feasibility outcomes of this pilot trial are as follows: (1) our ability to recruit 40 patients in 6 months, (2) achieve ≥75% treatment adherence among patients, and (3) <15% loss to follow-up. Secondary outcomes are the effects of MPL-001 relative to placebo on PPSP, opioid use, peri-operative pain interference, physical and emotional function, return to functioning, sleep, and adverse events (AEs) up to 6 months post-surgery. DISCUSSION: The results of our pilot study will inform the feasibility of a definitive trial to establish the effectiveness of CBD to reduce PPSP after TKA. If no major changes to our protocol are required, we will treat this study as a vanguard trial and enroll our pilot patients into a definitive trial. TRIAL REGISTRATION: We prospectively registered our trial on ClinicalTrials.gov (identifier: NCT03825965) before enrolling any patients.