A randomized, double-blind, dose-ranging study comparing wound infiltration of DepoFoam bupivacaine, an extended-release liposomal bupivacaine, to bupivacaine HCl for postsurgical analgesia in total knee arthroplasty

Abstract

IntroductionDepoFoam bupivacaine is a novel liposomal formulation of bupivacaine designed to provide prolonged postsurgical analgesia. This dose-ranging study evaluated extent and duration of analgesia following administration of DepoFoam bupivacaine in patients undergoing total knee arthroplasty (TKA). MethodsEfficacy, safety, and pharmacokinetics of DepoFoam bupivacaine doses of 133, 266, 399, or 532mg were compared with bupivacaine HCl (150mg) with epinephrine given as single injections via wound infiltration in TKA patients (N=138). Primary efficacy measure was AUC of pain intensity scores assessed by numeric rating scale with activity (NRS-A) through Day 4 postsurgery. Other assessments included pain intensity at rest (NRS-R), postsurgical opioid consumption, and safety, among others. ResultsMean AUC of NRS-A scores through Day 4 were 20.7, 19.5, 18.8, and 19.1 for the 133-mg, 266-mg, 399-mg, and 532-mg DepoFoam bupivacaine groups vs 20.4 for bupivacaine HCl. With DepoFoam bupivacaine 532-mg, differences in NRS-R scores reached statistical significance (P<0.05) vs bupivacaine HCl on Days 1 and 5 and mean AUC NRS-R scores were significantly lower through Days 2–5; a dose–response trend was demonstrated. Mean rating for blinded care provider's satisfaction with analgesia was significantly higher for DepoFoam bupivacaine 532mg vs bupivacaine HCl (P≤0.05). Other efficacy measures showed no statistically significant differences. ConclusionExposure to bupivacaine increased in a dose-related manner, as reflected by mean and maximum plasma bupivacaine concentrations, and AUC0−∞. Treatment with DepoFoam bupivacaine 532mg was associated with statistically significantly greater analgesia while patients were at rest after surgery compared with bupivacaine HCl.