HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in herniorrhaphy: results from the phase 3 EPOCH 2 study

• Published in: Hernia : the journal of hernias and abdominal wall surgery Vol. 23; no. 6; pp. 1071 - 1080
• Main Authors: Viscusi, E., Minkowitz, H., Winkle, P., Ramamoorthy, S., Hu, J., Singla, N.
• Format: Journal Article
• Language: English
• Published: Paris Springer Paris 01.12.2019; Springer Nature B.V
• Subjects: Abdominal Surgery; Adult; Analgesia; Analgesics, Opioid - administration & dosage; Anesthetics; Anesthetics, Local - administration & dosage; Bupivacaine; Bupivacaine - administration & dosage; Chronic Pain; Double-Blind Method; Female; Hernia, Inguinal - surgery; Herniorrhaphy; Humans; Local anesthetics; Male; Medicine; Medicine & Public Health; Meloxicam; Meloxicam - administration & dosage; Middle Aged; Narcotics; Opioids; Original; Original Article; Pain; Pain Management; Pain Measurement; Pain perception; Pain, Postoperative - diagnosis; Pain, Postoperative - etiology; Pain, Postoperative - prevention & control; Toxicity; Postoperative pain; HTX-011; Opioid sparing; Multimodal analgesia; Inguinal hernia repair; Pain management
• ISSN: 1265-4906; 1248-9204; 1248-9204
• DOI: 10.1007/s10029-019-02023-6

Purpose Currently available local anesthetics have not demonstrated sufficient analgesia beyond 12–24 h postoperatively. The purpose of the study was to assess the safety and efficacy of HTX-011 (bupivacaine and meloxicam in Biochronomer ® polymer technology), a long-acting investigational anesthetic, in reducing both postoperative pain over 72 h and postoperative opioid use compared to bupivacaine hydrochloride (HCl). Methods A phase 3, randomized, double-blind, active-controlled multi-center study (EPOCH 2; NCT03237481) in subjects undergoing unilateral open inguinal herniorrhaphy with mesh placement was performed. Subjects randomly received a single intraoperative dose of HTX-011, immediate-release bupivacaine HCl, or saline placebo prior to closure. Results The study evaluated 418 subjects, and the primary and all key secondary efficacy endpoints were in favor of HTX-011. HTX-011 reduced mean pain intensity by 23% versus placebo (primary endpoint; p  < 0.001) and by 21% versus bupivacaine HCl ( p  < 0.001) with significant reductions in the number of patients experiencing severe pain. Opioid consumption over 72 h was reduced by 38% versus placebo ( p  < 0.001) and 25% versus bupivacaine HCl ( p  = 0.024). Overall, 51% of HTX-011 subjects were opioid-free through 72 h (versus 22% for placebo [ p  < 0.001] and 40% for bupivacaine HCl [ p  = 0.049]). HTX-011 was generally well-tolerated with fewer opioid-related adverse events reported compared to the bupivacaine HCl and placebo and no evidence of local anesthetic systemic toxicity. Conclusions HTX-011 demonstrated significant improvement in postoperative pain control and a clinically meaningful reduction in opioid consumption when compared to the most widely used local anesthetic, bupivacaine HCl.