Liposomal Bupivacaine Versus Plain Bupivacaine After Intercostal Injections For Pain Management After Thoracoscopy

NCT03737292 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 10129
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess pharmacokinetics of liposomal bupivacaine (Exparel) after multilevel intercostal injections of this local anesthetic for pain control during and after thoracoscopic surgeries. The specific aim of this study is to evaluate plasma concentration of bupivacaine after intraoperative intercostal injections of 266 mg of liposomal bupivacaine and compare it to plasma concentrations of bupivacaine after intercostal injections of 2mg/kg of 0.5% plain Bupivacaine with maximal dose of 30 ml or 150 mg. The hypothesis of the study is that plasma concentration of bupivacaine after intercostal injections of 266 mg of liposomal bupivacaine will be similar to concentrations after injections of plain bupivacaine, and will remain below the toxic level threshold range of 2000-3000 ng/mL (2-3 mg/L) at which central nervous system and cardiovascular adverse events would be expected to occur. The secondary objective is to evaluate if intercostal injections of 266 mg of liposomal bupivacaine will significantly reduce opioid consumption and postsurgical pain, within the first 48 hours and up to 3 months after minimally invasive thoracic surgeries, to determine if both acute and chronic post-thoracotomy pain can be decreased by intraoperative intercostal injections of liposomal bupivacaine. Additionally, the rate of pneumonia, the rate of atrial fibrillation and length of hospital stay will be assessed as secondary outcomes after thoracic surgeries. These outcomes can be affected by the level of postoperative pain and inflammation. Significance of this study: If positive, the results of this research have the potential to significantly improve pain management after thoracoscopic surgery. Based on prior experience, prolonged analgesia after liposomal bupivacaine injection is safe, and may help reduce perioperative opioid consumption and decrease opioid related complications. It will improve patient comfort, eliminate need for indwelling neuraxial catheters and risks associated with them.

Conditions

Pain, Postoperative; Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Plasma concentration of bupivacaine

  The primary end points to be measured in the study are plasma concentrations of bupivacaine 0.5, 1, 2, 4, 8, 12, 24, 32, 48 hours after intraoperative multiple level intercostal injections of plain Bupivacaine or Exparel. If the patient remains in the hospital, additional samples will be collected at 72 hours. If the patient gets discharged before this time, the last sample will be drawn at time of discharge from the hospital.

  0.5, 1, 2, 4, 8, 12, 24, 32, 48, 72 hours after intraoperative multiple level intercostal injections.

Study Arms (2)

Exparel

EXPERIMENTAL

Intercostal injection of 266mg of Exparel diluted to 30 ml.

Drug: Exparel

Bupivacaine

ACTIVE COMPARATOR

Intercostal injection of 0.5% Bupivacaine 2 mg/kg dose diluted to 30 ml.

Drug: Bupivacaine

Interventions

Exparel DRUG

The intercostal blocks will be performed at several levels corresponding to the incisions and chest tube insertion sites + two levels above and two levels below the incisions. On average, 5-6 intercostal spaces will be injected with 4-5 ml of local anesthetic at each level.

Exparel

Bupivacaine DRUG

The intercostal injections of 0.5% Bupivacaine 2 mg/kg dose diluted to 30 ml total will be performed at several levels corresponding to the incisions and chest tube insertion sites + two levels above and two levels below the incisions.

Bupivacaine

Eligibility Criteria

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

You may qualify if:

• \. Male or female patients over age 18 undergoing minimally invasive thoracic surgeries including but not limited to:
• VATS wedge resection /segmentectomy
• VATS lobectomy.
• Robot assisted thoracoscopic wedge resection/segmentectomy.
• Robot assisted thoracoscopic lobectomy procedures.

You may not qualify if:

• Patients under18 years of age
• Patients weighing less than 48 kg
• Pregnant and lactating females will be excluded from the trial
• Patients preoperatively taking narcotics for chronic pain in proximity to surgical site
• Patients with previous ipsilateral thoracic surgery
• Patients undergoing pleurectomy/mechanical pleurodesis.
• Patients with high likelihood of conversion from thoracoscopic procedure to open thoracotomy as determined by an operating surgeon
• Patients with pre-existing painful conditions (CRIPS, fibromyalgia, neuropathy)
• Patients unable to reliably communicate pain scores such as patients with dementia, alterations in mental status
• Patients with hypersensitivity to local anesthetics and pain medications used in the study
• Patients with previous thoracic spine surgeries
• Patients with increased creatinine (over 1.5mg/dl)
• Patients with liver dysfunction
• Non-English speaking patients

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead

Study Sites (1)

Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

RECRUITING

Related Publications (7)

• Scott DB. Evaluation of the toxicity of local anaesthetic agents in man. Br J Anaesth. 1975 Jan;47(1):56-61. doi: 10.1093/bja/47.1.56.

  PMID: 1096908 BACKGROUND

• Richard BM, Rickert DE, Doolittle D, Mize A, Liu J, Lawson CF. Pharmacokinetic Compatibility Study of Lidocaine with EXPAREL in Yucatan Miniature Pigs. ISRN Pharm. 2011;2011:582351. doi: 10.5402/2011/582351. Epub 2011 Dec 27.

  PMID: 22389853 BACKGROUND

• Scott DB, Lee A, Fagan D, Bowler GM, Bloomfield P, Lundh R. Acute toxicity of ropivacaine compared with that of bupivacaine. Anesth Analg. 1989 Nov;69(5):563-9.

  PMID: 2679230 BACKGROUND

• Knudsen K, Beckman Suurkula M, Blomberg S, Sjovall J, Edvardsson N. Central nervous and cardiovascular effects of i.v. infusions of ropivacaine, bupivacaine and placebo in volunteers. Br J Anaesth. 1997 May;78(5):507-14. doi: 10.1093/bja/78.5.507.

  PMID: 9175963 BACKGROUND

• Neal JM, Barrington MJ, Fettiplace MR, Gitman M, Memtsoudis SG, Morwald EE, Rubin DS, Weinberg G. The Third American Society of Regional Anesthesia and Pain Medicine Practice Advisory on Local Anesthetic Systemic Toxicity: Executive Summary 2017. Reg Anesth Pain Med. 2018 Feb;43(2):113-123. doi: 10.1097/AAP.0000000000000720.

  PMID: 29356773 BACKGROUND

• Khalil KG, Boutrous ML, Irani AD, Miller CC 3rd, Pawelek TR, Estrera AL, Safi HJ. Operative Intercostal Nerve Blocks With Long-Acting Bupivacaine Liposome for Pain Control After Thoracotomy. Ann Thorac Surg. 2015 Dec;100(6):2013-8. doi: 10.1016/j.athoracsur.2015.08.017. Epub 2015 Oct 24.

  PMID: 26507422 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

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Bupivacaine

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Zoulfira Nisnevitch-Savarese, MD

  Penn State Hershey College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zoulfira Nisnevitch-Savarese, MD

CONTACT

717-531-4264; znisnevitchsavarese@pennstatehealth.psu.edu

Christopher Cowart, MD

CONTACT

717-531-4264; ccowart@pennstatehealth.psu.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Anesthesiology & Perioperative Medicine

Model Details: This is a prospective randomized controlled, double blind study.

Study Record Dates

• First Submitted: November 8, 2018
• First Posted: November 9, 2018
• Study Start: April 9, 2019
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: June 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)