A Phase 3 Active-Controlled Trial of Liposomal Bupivacaine via Adductor Canal Block for Total Knee Arthroplasty

Abstract

Background: The efficacy, safety, pharmacokinetics, and pharmacodynamics of liposomal bupivacaine combined with bupivacaine hydrochloride administered via adductor canal block for total knee arthroplasty were evaluated. Methods: This randomized, double-blind, active-controlled, multicenter trial (NCT05139030) enrolled adults undergoing primary unilateral total knee arthroplasty. Participants were randomized 1:1 to receive an adductor canal block administered as a single dose of liposomal bupivacaine 133 mg admixed with bupivacaine hydrochloride 50 mg (liposomal bupivacaine group) or bupivacaine hydrochloride 50 mg admixed with saline (bupivacaine group). The study enrolled 167 participants (liposomal bupivacaine group, n = 85; bupivacaine group, n = 82). The primary endpoint was the area under the curve of numerical rating scale pain intensity scores from 0 to 96 hours postsurgery. Results: From zero to 96 hours after surgery, the least squares mean (LSM) (SE) of the area under the curve of the numerical rating scale pain intensity score was lower in the liposomal bupivacaine group (568.9 [20.07]) versus the bupivacaine group (634.7 [20.04]) (LSM difference versus bupivacaine, ‒65.8 [95% CI (confidence interval), ‒118.7 to ‒12.9]; P = 0.0074). In the liposomal bupivacaine group, total opioid consumption was lower from 0 to 96 hours versus the bupivacaine group (LSM [95% CI], 101.8 [89.1 to 116.3] versus 132.8 [116.3 to 151.7] morphine milligram equivalents; LSM ratio relative to bupivacaine [95% CI], 0.77 [0.64 to 0.92]; P = 0.0018). The median time to first opioid consumption after surgery was longer for the liposomal bupivacaine group (median [interquartile range], liposomal bupivacaine, 4.2 hours [2.7 to 6.1]; bupivacaine, 3.6 hours [2.5 to 4.8]; P = 0.0127). Treatment-related adverse event incidence was similar between groups (liposomal bupivacaine: 3.5%; bupivacaine: 2.5%). Conclusions: Liposomal bupivacaine administered via adductor canal block for total knee arthroplasty was associated with concurrent reductions in pain and opioid consumption compared with bupivacaine during the first 96 hours after surgery.