Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03708198
Other study ID # 180006
Secondary ID
Status Completed
Phase Phase 4
First received
Last updated
Start date June 11, 2018
Est. completion date August 11, 2020

Study information

Verified date May 2022
Source University of Virginia
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

In this study, patients who are undergoing thoracotomies will be consented separately from the surgery itself. Patients will be consented for the study in the surgical clinic or on the day of the surgery in the Surgical Admission Suites (SAS), prior to being taken to the OR. 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. Immediately prior to the injection of the local anesthetic, 5 ml of blood will be drawn from the patient via the arterial line. The arterial line will be placed as part of standard surgery procedure and not for the purposes of the study. Blood will then be drawn from the patient after the injection of the local anesthetic at 5 mins, 15 mins, 30 mins, 1, 2, 4, 8, 12, 24, 48, 72 and 96 h. Each blood draw will be 5 ml. Blood will be drawn a total of 13 times. The arterial line will not remain in the patient for the purposes of the study and will be removed per standard procedure. If more blood samples are needed after the arterial line is removed, we will first attempt to obtain blood an existing venous catheter. If blood cannot be obtained this way, a venipuncture will be performed. Blood samples will be analyzed for the following pharmacokinetic parameters: area under the serum concentration-time infinity (AUC), maximum observed serum concentration (Cmax), time to attain Cmax (Tmax), and apparent terminal elimination half-life (T1/2). At the time blood samples are drawn, pain scores will be recorded on a standard ten-point pain scale. These pain scores will be omitted if the patient is under general anesthesia.


Recruitment information / eligibility

Status Completed
Enrollment 15
Est. completion date August 11, 2020
Est. primary completion date October 11, 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - over 18 years of age - Undergoing thoracotomy Exclusion Criteria: - Non-English speaking - Pregnant women (self reported) - Prisoners - Weighing <50 kg - Allergy to local anesthetics - Unable to consent for themselves

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Liposomal Bupivacaine
intercostal block

Locations

Country Name City State
United States University of Virginia Health System Charlottesville Virginia

Sponsors (1)

Lead Sponsor Collaborator
University of Virginia

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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
See also
  Status Clinical Trial Phase
Completed NCT06049264 - Thoracic Spine Manual Traction With Mobilization Versus Manipulation N/A
Completed NCT04251637 - Non Invasive Cardiac Output Evaluation With Starling SV for Lung Elective Surgery
Withdrawn NCT05100160 - Gabapentin for the Reduction of Opiate Use Following Pulmonary Resection (GROUP Trial) Phase 3
Not yet recruiting NCT04546594 - Epidemiological Data on Pain
Terminated NCT03962036 - Effect of One-lung Ventilation on BIS Values
Completed NCT05091281 - Macintosh Versus GlideScope Versus C-MAC for Double Lumen Endotracheal Intubation N/A
Completed NCT05091398 - Erector Spinae Plane, Paravertebral Versus Intercostal Nerve Block for VATS Surgery N/A
Completed NCT01476761 - MicroCutter in Surgical Stapling - European Trial I Phase 4
Active, not recruiting NCT06252740 - Investigation of Regional Interdependence of the Hip and Spine in Baseball Players With Low Back Pain
Recruiting NCT06075316 - Improving Thoracic Surgical Care Using Electronic Patient-Reported Outcomes (ePROS) N/A
Completed NCT05392517 - Effects of Self-mobilization Techniques in Chronic Thoracic Pain N/A
Completed NCT05395078 - Effects of Thoracic Extension Versus Thoracic Stabilization Exercises in Patients With Maigne's Thoracic Pain N/A
Active, not recruiting NCT05798585 - Comparing Erector Spinae Plane (ESP) and Thoracic Paravertebral (TPV) Block Analgesic Effect After Elective VATS N/A
Not yet recruiting NCT06253741 - Rhomboid Intercostal and Subserratus / Paravertebral Block N/A
Completed NCT05204537 - The Role of Surgery in Patients With Coronavirus Disease - 19 (COVID-19) Related Thoracic Complications
Completed NCT04246099 - Opioid-free Anesthesia in Thoracic Surgery
Not yet recruiting NCT06434727 - Evaluating Intuitive 3D Models in Preoperative Surgical Planning for Thoracic and Colorectal Procedures.
Terminated NCT02259452 - Radiation Induced Cardiopulmonary Injury in Humans
Completed NCT04964973 - Effect of Transcutaneous Electro-stimulation in Ambulatory Postoperative Rehabilitation Treatment in Thoracic Surgery. N/A
Completed NCT06310850 - The Effect of Preprocedural Subanesthetic Ketamine on Pain and Anxiety Phase 3