Pharmacokinetics of Single-Dose Liposomal Bupivacaine in Surgeon Performed Intercostal Nerve Blocks

NCT03708198 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 180006
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Post-surgery pain management is critical for ensuring timely patient recovery and minimizing complications. Part of the multimodal approach to managing severe acute pain in the days following surgeries is the use of nerve blocks. The relatively short-lived effect of commonly used local anesthetics recently prompted the development and subsequent approval of a liposomal formulation of bupivacaine (Exparel; Pacira Pharmaceuticals, Parsippany, New Jersey). It has demonstrated favorable pharmacokinetics compared to bupivacaine HCl(hydrochloride), with a slower release into blood stream of up to 96 hours after administration, following a single dose wound infiltration at the end of various surgeries. Studies using other modes of administration reported similar results. Thoracic surgeries pose an exceptional challenge as they are one of the most painful surgeries and poor pain-management contributes to reduced quality of life and severely delayed recovery. The anesthesiology protocol within the Enhanced Recovery After Surgery (ERAS) program at medical centers across the world aim to increase patient comfort after surgery while reducing complications and use of opioids. As a common part of this protocol, intercostal nerve blocks with liposomal bupivacaine are regularly utilized for reduction of post-thoracotomy pain and studies show that it may be just as or more effective than bupivacaine HCl for treatment of pain, decreasing hospital stays and reducing the incidence of complications. Despite its frequent use in the surgical room for nerve blocks, the pharmacokinetics of a single dose injection of liposomal bupivacaine at the intercostal nerves has never been investigated. The aim of this study is to assess the pharmacokinetics of liposomal bupivacaine injected at the intercostal nerves. The results of this small-scale study will aid in the development of larger such studies in the future, and may aid in the standardization of post-thoracotomy pain management. Specifically, the information gleaned from this study will allow for the optimal use of additional local anesthetics, particularly those administered intravenously, for the purpose of obtaining maximal pain relief while minimizing the occurrence of local anesthetic toxicity.

Conditions

Thoracic

Outcome Measures

Primary Outcomes (1)

• Tmax, or the Time Until the Maximum Concentration

  the tmax, or the time until the maximum concentration

  until study completion, which is 6 months on average

Study Arms (1)

Intercostal Nerve Block

OTHER

The study participants will be given a standard 266 mg single dose injection of liposomal bupivacaine by the surgeon at the start of the surgery.

Drug: Liposomal Bupivacaine

Interventions

Liposomal Bupivacaine DRUG

intercostal block

Intercostal Nerve Block

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• over 18 years of age
• Undergoing thoracotomy

You may not qualify if:

• Non-English speaking
• Pregnant women (self reported)
• Prisoners
• Weighing \<50 kg
• Allergy to local anesthetics
• Unable to consent for themselves

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Related Publications (5)

• Hu D, Onel E, Singla N, Kramer WG, Hadzic A. Pharmacokinetic profile of liposome bupivacaine injection following a single administration at the surgical site. Clin Drug Investig. 2013 Feb;33(2):109-15. doi: 10.1007/s40261-012-0043-z.

  PMID: 23229686 BACKGROUND

• Davidson EM, Barenholz Y, Cohen R, Haroutiunian S, Kagan L, Ginosar Y. High-dose bupivacaine remotely loaded into multivesicular liposomes demonstrates slow drug release without systemic toxic plasma concentrations after subcutaneous administration in humans. Anesth Analg. 2010 Apr 1;110(4):1018-23. doi: 10.1213/ANE.0b013e3181d26d2a.

  PMID: 20357145 BACKGROUND

• De Cosmo G, Aceto P, Gualtieri E, Congedo E. Analgesia in thoracic surgery: review. Minerva Anestesiol. 2009 Jun;75(6):393-400. Epub 2008 Oct 27.

  PMID: 18953284 BACKGROUND

• Mehran RJ, Walsh GL, Zalpour A, Cata JP, Correa AM, Antonoff MB, Rice DC. Intercostal Nerve Blocks With Liposomal Bupivacaine: Demonstration of Safety, and Potential Benefits. Semin Thorac Cardiovasc Surg. 2017 Winter;29(4):531-537. doi: 10.1053/j.semtcvs.2017.06.004. Epub 2017 Jun 6.

  PMID: 29698654 BACKGROUND

• Rice DC, Cata JP, Mena GE, Rodriguez-Restrepo A, Correa AM, Mehran RJ. Posterior Intercostal Nerve Block With Liposomal Bupivacaine: An Alternative to Thoracic Epidural Analgesia. Ann Thorac Surg. 2015 Jun;99(6):1953-60. doi: 10.1016/j.athoracsur.2015.02.074. Epub 2015 Apr 23.

  PMID: 25912739 BACKGROUND

Results Point of Contact

• Title: William Manson, MD
• Organization: UVA Health

wcm6m@virginia.edu

4349242283

Study Officials

• William Manson, MD

  UVA Department of Anesthesiology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Anesthesiology

Study Record Dates

• First Submitted: June 8, 2018
• First Posted: October 17, 2018
• Study Start: June 11, 2018
• Primary Completion: October 11, 2019
• Study Completion: August 11, 2020
• Last Updated: May 23, 2022
• Results First Posted: May 23, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)