Category: Professional Posters
Purpose: HTX-011 is a novel extended-release dual-acting local anesthetic combining bupivacaine with low-dose meloxicam in a Biochronomer polymer. In a Phase 3 herniorrhaphy study (EPOCH 2), treatment with HTX-011 without background multimodal analgesia (MMA) provided superior pain relief, significantly reduced the incidence of severe pain and total opioid consumption, and resulted in significantly more opioid-free patients through 72 hours than either placebo or bupivacaine hydrochloride. This follow-on study was conducted to evaluate the efficacy and safety of HTX-011 when given as the foundation of a scheduled non-opioid MMA regimen that includes nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen.
Methods: This was an open-label follow-on study to the Phase 3 trial in patients undergoing unilateral, open inguinal herniorrhaphy including 2 sequential cohorts. In both cohorts, patients received HTX-011 300 mg/9 mg (bupivacaine/meloxicam) administered via needle-free application into the surgical site. The nonopioid MMA regimen consisted of preoperative oral acetaminophen 1 g and postoperative oral ibuprofen 600 mg and oral acetaminophen 1 g, each given every 6 hours (alternating every 3 hours) throughout the 72-hour inpatient postoperative period. Patients in cohort 2 also received intravenous ketorolac intraoperatively as part of the MMA regimen. Upon discharge, patients were instructed to manage pain with oral ibuprofen 600 mg every 6 hours as needed and add oral acetaminophen 1 g every 6 hours if needed. The primary efficacy endpoint was the proportion of patients who remained opioid-free through 72 hours after surgery. Secondary endpoints included the proportion of patients who remained opioid-free through recovery on days 10 and 28, total opioid consumption, and the proportion of patients in severe pain (numeric rating scale [NRS] ≥7) at any time through 72 hours after surgery.
Results: Across both cohorts 63 patients were treated. More than 90% of patients who received HTX-011 and a non-opioid MMA regimen did not require opioids to manage their postoperative pain for 72 hours after surgery; in comparison, 51%, 40%, and 22% of patients were opioid-free from the Phase 3 study who received HTX-011, bupivacaine hydrochloride, and placebo, respectively, when no MMA was employed. Among the patients who were opioid-free through 72 hours in this study, 96.5% remained opioid-free through Day 10 and 91.2% remained opioid-free through Day 28. Mean ± SE total postoperative opioid consumption was 0.9 ± 0.41 milligram morphine equivalents overall. The proportion of patients with severe pain during the 72-hour postoperative period was 17.5% across both cohorts. Mean pain scores were mild throughout the 72-hour period (NRS < 4). Intravenous ketorolac did not provide additional efficacy benefit. Overall, 24 (38.1%) patients experienced an adverse event (AE); this number was comparatively lower than the incidence of AEs observed in the Phase 3 study, because of the lower rates of opioid-related AEs. There were no new safety signals associated with the use of ibuprofen, acetaminophen, or ketorolac together with HTX-011, including no evidence of NSAID-related cardiovascular, gastrointestinal, or renal toxicity.
Conclusion: The use of HTX-011 as the foundation of a scheduled non-opioid MMA regimen enabled the majority of patients to remain in mild pain with more than 90% of patients remaining opioid-free through 72 hours. This may translate to a reduced need for opioid prescriptions at discharge. The high proportion of opioid-free patients led to fewer opioid-related AEs and fewer overall AEs than in the Phase 3 study. This study demonstrated that HTX-011 can safely be administered with other NSAIDs and acetaminophen.