TY - JOUR
T1 - A phase 3 active-controlled trial of liposomal bupivacaine via sciatic nerve block in the popliteal fossa after bunionectomy
AU - Schwartz, Gary
AU - Gadsden, Jeffrey C.
AU - Gonzales, Jeffrey
AU - Hutchins, Jacob
AU - Song, Jia
AU - Brady, O'Dane D.
AU - DiGiorgi, Mary
AU - Winston, Roy
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/6
Y1 - 2024/6
N2 - Study objective: 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. Design: Two-part, randomized, double-blind, active-controlled trial (NCT05157841). Setting: Operating room, postanesthesia care unit, and health care facility (6 sites). Patients: Adults with American Society of Anesthesiologists physical status classification ≤3 and body mass index ≥18 to <40 kg/m2 undergoing elective distal metaphyseal osteotomy. Interventions: 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. Measurements: 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. Main results: 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. Conclusions: 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.
AB - Study objective: 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. Design: Two-part, randomized, double-blind, active-controlled trial (NCT05157841). Setting: Operating room, postanesthesia care unit, and health care facility (6 sites). Patients: Adults with American Society of Anesthesiologists physical status classification ≤3 and body mass index ≥18 to <40 kg/m2 undergoing elective distal metaphyseal osteotomy. Interventions: 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. Measurements: 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. Main results: 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. Conclusions: 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.
KW - Bupivacaine
KW - Hallux valgus
KW - Liposomes
KW - Nerve blocks
KW - Nonopioid analgesic
KW - Postoperative pain
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U2 - 10.1016/j.jclinane.2024.111402
DO - 10.1016/j.jclinane.2024.111402
M3 - Article
C2 - 38340677
AN - SCOPUS:85184568511
SN - 0952-8180
VL - 94
JO - Journal of Clinical Anesthesia
JF - Journal of Clinical Anesthesia
M1 - 111402
ER -