A Randomized, Multicenter, Double-Blind Study of Local Infiltration Analgesia with Liposomal Bupivacaine for Postsurgical Pain Following Total Knee Arthroplasty: Rationale and Design of the Pillar Trial.

Liposomal bupivacaine, a prolonged-release formulation of bupivacaine hydrochloride, is indicated for infiltration into the surgical site for postsurgical analgesia. Results from previous total knee arthroplasty (TKA) studies suggest that analgesic efficacy associated with liposomal bupivacaine may be impacted by variability in infiltration technique. The PILLAR study is designed to assess liposomal bupivacaine efficacy in TKA using a standardized infiltration protocol. Materials and Methods/Design: This phase 4, multicenter, randomized, double-blind, controlled, parallel-group study will compare the safety and efficacy of infiltration with liposomal bupivacaine versus standard bupivacaine for postsurgical pain control in adults undergoing primary unilateral TKA. All subjects will receive a standardized pre-surgical analgesic regimen, and will be randomized to receive either liposomal bupivacaine 266 mg/20 mL (admixed with standard bupivacaine 0.5% 20 mL and expanded to a total volume of 120 mL) or bupivacaine 0.5% 20 mL (expanded to a total volume of 120 mL). The study drug will be infiltrated using six syringes (prefilled with 20 mL of study drug solution) to deliver 1-1.5 mL infusions into prespecified periarticular tissues. All subjects will receive standardized postsurgical analgesia and access to rescue medication. The co-primary efficacy endpoints are area under the curve of visual analog scale pain intensity scores from 12-48 hours postsurgery and total postsurgical opioid consumption from 0-48 hours. Secondary efficacy endpoints include other pain assessments, time to first use of rescue medication, discharge readiness, use of skilled nursing facilities, and hospital length of stay. Safety will be evaluated based on adverse events.The use of a standardized protocol comparing infiltration of equal volumes of the study drug, designed by experienced investigators to ensure complete coverage of all areas innervating the surgical site while minimizing leakage of study drug, will help define the role of liposomal bupivacaine in the setting of TKA.