A phase 3 active-controlled trial of liposomal bupivacaine via sciatic nerve block in the popliteal fossa after bunionectomy.

To investigate the efficacy, safety, pharmacodynamics, and pharmacokinetics of liposomal bupivacaine (LB) administered via ultrasound-guided sciatic nerve block in the popliteal fossa in participants undergoing bunionectomy. Two-part, randomized, double-blind, active-controlled trial (NCT05157841). Operating room, postanesthesia care unit, and health care facility (6 sites). Adults with American Society of Anesthesiologists physical status classification ≤3 and body mass index ≥18 to <40 kg/m Part A participants were randomized 1:1:1 to LB 266 mg, LB 133 mg, or bupivacaine hydrochloride 50 mg (BUPI). Part B participants were randomized 1:1 to LB (at the dose established by part A) or BUPI. The primary endpoint was area under the curve (AUC) of numerical rating scale (NRS) pain intensity scores 0-96 h after surgery. Secondary endpoints included total postsurgical opioid consumption, opioid-free status 0-96 h after surgery, and pharmacokinetic endpoints. Part A enrolled 22 participants per group. In part B, additional participants were randomized to LB 133 mg (n = 59) and BUPI (n = 60) (185 total). LB 133 mg had significant reductions versus BUPI in the AUC of NRS pain intensity score (least squares mean [LSM], 207.4 vs 371.4; P < 0.00001) and total opioid consumption 0-96 h after surgery (LSM, 17.7 [95% confidence interval (CI), 13.7, 22.8] morphine milligram equivalents [MMEs] vs 45.3 [95% CI, 35.1, 58.5] MMEs; P < 0.00001) and an increased proportion of opioid-free participants (24.4% vs 6%; odds ratio, 5.04 [95% CI, 2.01, 12.62]; P = 0.0003) in parts A + B. Adverse events were similar across groups. LB 133 mg administered via sciatic nerve block in the popliteal fossa after bunionectomy demonstrated superior and long-lasting postsurgical pain control versus BUPI. The clinical relevance of these findings is supported by concurrent reductions in pain and opioid consumption over 4 days after surgery and a significantly greater percentage of participants remaining opioid-free.

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Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gary Schwartz reports financial support was provided by Pacira BioSciences, Inc. Jeffrey C. Gadsden reports financial support was provided by Pacira BioSciences, Inc. Jeffrey Gonzales reports financial support was provided by Pacira BioSciences, Inc. Jacob Hutchins reports financial support was provided by Pacira BioSciences, Inc. Gary Schwartz reports a relationship with Pacira BioSciences, Inc. that includes: consulting or advisory. Gary Schwartz reports a relationship with Dorsal Health that includes: consulting or advisory. Jeffrey C. Gadsden reports a relationship with Pacira BioSciences, Inc. that includes: consulting or advisory. Jeffrey Gonzales reports a relationship with Pacira BioSciences, Inc. that includes: employment. Jacob Hutchins reports a relationship with Pacira BioSciences, Inc. that includes: consulting or advisory. Jacob Hutchins reports a relationship with Insitu Biologics, Inc. that includes: consulting or advisory and equity or stocks. Jacob Hutchins reports a relationship with AceIRX that includes: consulting or advisory. Jacob Hutchins reports a relationship with AtriCure that includes: consulting or advisory. Jia Song reports a relationship with Pacira BioSciences, Inc. that includes: employment and equity or stocks. O'Dane Brady reports a relationship with Pacira BioSciences, Inc. that includes: employment and equity or stocks. Mary DiGiorgi reports a relationship with Pacira BioSciences, Inc. that includes: employment and equity or stocks. Roy Winston reports a relationship with Pacira BioSciences, Inc. that includes: employment and equity or stocks.