• 1. 

    Gan TJ, Habib AS & Miller TE et al.: Incidence, patient satisfaction, and perceptions of post-surgical pain: results from a US national survey. Curr Med Res Opin 30: 149, 2014.

    • Crossref
    • PubMed
    • Web of Science
    • Search Google Scholar
    • Export Citation
  • 2. 

    Svensson I, Sjostrom B & Haljamae H: Assessment of pain experiences after elective surgery. J Pain Symptom Manage 20: 193, 2000.

  • 3. 

    Viscusi E, Gimbel JS & Pollak RA et al.: HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in bunionectomy: phase III results from the randomized EPOCH 1 study. Reg Anesth Pain Med 44: 700, 2019.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. 

    Golembiewski J & Dasta J: Evolving role of local anesthetics in managing postsurgical analgesia. Clin Ther 37: 1354, 2015.

    • Crossref
    • PubMed
    • Web of Science
    • Search Google Scholar
    • Export Citation
  • 5. 

    Kehlet H & Andersen LO: Local infiltration analgesia in joint replacement: the evidence and recommendations for clinical practice. Acta Anaesthesiol Scand 55: 778, 2011.

    • Crossref
    • PubMed
    • Web of Science
    • Search Google Scholar
    • Export Citation
  • 6. 

    Braito M, Dammerer D & Schlager A et al.: Continuous wound infiltration after hallux valgus surgery. Foot Ankle Int 39: 180, 2018.

    • Crossref
    • PubMed
    • Web of Science
    • Search Google Scholar
    • Export Citation
  • 7. 

    Dasta J, Ramamoorthy S & Patou G et al.: Bupivacaine liposome injectable suspension compared with bupivacaine HCl for the reduction of opioid burden in the postsurgical setting. Curr Med Res Opin 28: 1609, 2012.

    • Crossref
    • PubMed
    • Web of Science
    • Search Google Scholar
    • Export Citation
  • 8. 

    Tw, Hamilton, Athanassoglou V & Mellon S et al.: Liposomal bupivacaine infiltration at the surgical site for the management of postoperative pain. Cochrane Database Syst Rev 2: CD011419, 2017.

    • Web of Science
    • Search Google Scholar
    • Export Citation
  • 9. 

    Enoch S & Leaper D: Basic science of wound healing. Surgery (Oxford) 23: 31, 2006.

  • 10. 

    Hargreaves KM & Keiser K: Local anesthetic failure in endodontics. Endod Top 1: 26, 2002.

  • 11. 

    Kessler ER, Shah M & Gruschkus SK et al.: Cost and quality implications of opioid-based postsurgical pain control using administrative claims data from a large health system: opioid-related adverse events and their impact on clinical and economic outcomes. Pharmacotherapy 33: 383, 2013.

    • Crossref
    • PubMed
    • Web of Science
    • Search Google Scholar
    • Export Citation
  • 12. 

    Ramachandran SK, Haider N & Saran KA et al.: Life-threatening critical respiratory events: a retrospective study of postoperative patients found unresponsive during analgesic therapy. J Clin Anesth 23: 207, 2011.

    • Crossref
    • PubMed
    • Web of Science
    • Search Google Scholar
    • Export Citation
  • 13. 

    Sun EC, Darnall BD & Baker LC et al.: Incidence of and risk factors for chronic opioid use among opioid-naive patients in the postoperative period. JAMA Intern Med 176: 1286, 2016.

    • Crossref
    • PubMed
    • Web of Science
    • Search Google Scholar
    • Export Citation
  • 14. 

    Brummett CM, Waljee JF & Goesling J et al.: New persistent opioid use after minor and major surgical procedures in US adults. JAMA Surg 152: e170504, 2017.

    • Crossref
    • PubMed
    • Web of Science
    • Search Google Scholar
    • Export Citation
  • 15. 

    Ottoboni T, Quart B & Pawasaukas J et al.: Mechanism of action of HTX-011: a novel, extended-release, dual-acting local anesthetic formulation for postoperative pain. Reg Anesth Pain Med 45: 117, 2020.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16. 

    Wang H, Gargano C & Lukac S et al.: An enhanced bunionectomy model as a potential tool for early decision-making in the development of new analgesics. Adv Ther 27: 963, 2010.

    • Crossref
    • PubMed
    • Web of Science
    • Search Google Scholar
    • Export Citation
  • 17. 

    Singla NK, Desjardins PJ & Chang PD: A comparison of the clinical and experimental characteristics of four acute surgical pain models: dental extraction, bunionectomy, joint replacement, and soft tissue surgery. Pain 155: 441, 2014.

    • Crossref
    • PubMed
    • Web of Science
    • Search Google Scholar
    • Export Citation
  • 18. 

    Essex MN, Zhang RY & Berger MF et al.: Safety of celecoxib compared with placebo and non-selective NSAIDs: cumulative meta-analysis of 89 randomized controlled trials. Expert Opin Drug Saf 12: 465, 2013.

    • Crossref
    • PubMed
    • Web of Science
    • Search Google Scholar
    • Export Citation
  • 19. 

    Viscusi E, Minkowitz H & Winkle P et al.: HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in herniorrhaphy: results from the phase 3 EPOCH 2 study. Hernia 23: 1071, 2019.

    • Crossref
    • PubMed
    • Web of Science
    • Search Google Scholar
    • Export Citation
  • 20. 

    Lachiewicz PF, Lee GC & Pollak R et al.: HTX-011 reduced pain and opioid use after primary total knee arthroplasty: results of a randomized phase 2b trial. J Arthroplast https://doi.org/10.1016/j.arth.2020.05.044, 2020.

    • Web of Science
    • Search Google Scholar
    • Export Citation
  • 21. 

    Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology 116: 248, 2012.

    • PubMed
    • Web of Science
    • Search Google Scholar
    • Export Citation
  • 22. 

    Chou R, Gordon DB & De Leon-Casaola OA et al.: Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain 17: 131, 2016.

    • Web of Science
    • Search Google Scholar
    • Export Citation
  • 23. 

    Daniels SE, Playne R & Stanescu I et al.: Efficacy and safety of an intravenous acetaminophen/ibuprofen fixed-dose combination after bunionectomy: a randomized, double-blind, factorial, placebo-controlled trial. Clin Ther 41: 1982, 2019.

    • Crossref
    • PubMed
    • Web of Science
    • Search Google Scholar
    • Export Citation
  • 24. 

    Hah JM, Bateman BT & Ratliff J et al.: Chronic opioid use after surgery: implications for perioperative management in the face of the opioid epidemic. Anesth Analg 125: 1733, 2017.

    • Crossref
    • PubMed
    • Web of Science
    • Search Google Scholar
    • Export Citation
  • 25. 

    Golf M, Daniels SE & Onel E: A phase 3, randomized, placebo-controlled trial of DepoFoam(R) bupivacaine (extended-release bupivacaine local analgesic) in bunionectomy. Adv Ther 28: 776, 2011.

    • Crossref
    • PubMed
    • Web of Science
    • Search Google Scholar
    • Export Citation

Opioid-Free Recovery from Bunionectomy with HTX-011, a Dual-Acting Local Anesthetic Combining Bupivacaine and Meloxicam, as the Foundation of Non-Opioid Multimodal Analgesia

Richard Pollak DPM, Danlin Cai PhD, and Tong J. Gan MD, MBA, MHS
View More View Less
Restricted access

Background

There is a need for postoperative pain control that minimizes or eliminates opioid use during the first 72 hours following surgery, when pain is most severe. HTX-011 is an extended-release, dual-acting local anesthetic that demonstrated superior 72-hour analgesia over standard of care bupivacaine hydrochloride (HCl) and saline placebo in a phase 3 bunionectomy study (EPOCH-1). Having shown HTX-011 monotherapy is superior to bupivacaine HCl in reducing postoperative pain intensity and opioid use, this follow-on study evaluated the safety and efficacy of HTX-011 as the foundation of a multimodal analgesia (MMA) regimen using over-the-counter medications recommended by practice guidelines for pain management.

Methods

Following regional anesthesia administered as a lidocaine block, patients underwent unilateral bunionectomy with osteotomy and internal fixation. Prior to closure, HTX-011 (up to 60 mg bupivacaine/1.8 mg meloxicam) was applied without a needle. Patients received scheduled postoperative MMA alternating ibuprofen (600 mg) and acetaminophen (1 g) every 3 hours for 72 hours. Efficacy was assessed based on pain intensity (numeric rating scale [NRS; 0–10]) and consumption of opioid rescue medication (intravenous morphine milligram equivalents [MME]). Adverse event and vital sign monitoring, plus laboratory and wound healing assessments, were used to determine safety.

Results

Over the 72-hour assessment period following bunionectomy, mean pain scores were mild in severity (NRS <4) and 22/31 patients (71%) experienced no severe pain (NRS ≥7) with HTX-011 as the foundation of scheduled, non-opioid MMA. Patients consumed an average of 1.61 MME total, with 24/31 (77%) requiring no opioid rescue medication (opioid-free). HTX-011 was well-tolerated and demonstrated no safety concerns with the inclusion of postoperative MMA.

Conclusions

HTX-011 as the foundation of an MMA regimen including scheduled ibuprofen and acetaminophen maintained mean postoperative pain scores in the mild range and enabled opioid-free recovery for 77% of bunionectomy patients through the 28-day recovery period.

Endeavor Clinical Trials, San Antonio, TX.

Heron Therapeutics, Inc, San Diego, CA.

Renaissance School of Medicine at Stony Brook University, Stony Brook, NY.

Corresponding author: Richard Pollak, DPM, Endeavor Clinical Trials, 8042 Wurzbach #420, San Antonio, TX 78229. (E-mail: rpollak@ergclinical.com)