Liposomal Bupivacaine for Pain Control Following Thoracic Surgery.

NCT ID: NCT03036085

Last Updated: 2017-01-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2/PHASE3

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-02-28

Study Completion Date

2017-12-31

Brief Summary

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The aims of the study are to compare the effectiveness and postoperative outcomes of liposomal bupivacaine vs plain bupivacaine following video-assisted thoracoscopic surgery. The investigators' hypothesis is that liposomal bupivacaine will decrease the postoperative pain and will be associated with more favorable postoperative outcomes when compared to plain bupivacaine following video-assisted thoracoscopic surgery.

Detailed Description

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Pain management remains a primary concern for many patients following thoracic surgery. Suboptimal analgesia leads to numerous postoperative complications like reduced cardiac, respiratory and gastrointestinal functions, more septic and thromboembolic complications, increased incidence of developing chronic pain states, increased mortality in high-risk patients with multiple comorbidities, and many others.

Opioids have a distinct role in the postoperative analgesia. Although opioids have positively affected surgery for decades, they are associated with a number of potentially severe side effects including prolonged ileus, nausea, vomiting, central nervous system and respiratory depression, development of hyperalgesia, and the risk of dependency and abuse. These adverse effects increase the overall cost of treatment for these patients and can potentially result in longer hospital stays.

Local infiltration and regional blocks of local anesthetics are increasingly utilized during thoracic surgery procedures as an alternative to epidural analgesia. Bupivacaine is widely used for intercostal nerve blocks but its utility is limited by its short duration of action (\<6 hours). Perineural catheters for continuous infusion of bupivacaine have been used to overcome this limitation but the need of expensive pumps and the risk of significant complications associated with the use of catheters (i.e. infection, septicemia, intravascular migration etc) has limited its use.

Encapsulation of local anesthetics into liposomes is a novel method which extends drug delivery. The use of multivesicular liposomes has been shown to provide a slow and steady release of local anesthetics for several days after nonvascular administration. Liposomal bupivacaine is a novel formulary of bupivacaine, is designed for a single-dose local infiltration into the surgical site and produces postsurgical analgesia for up to 72-96 hours.

Liposomal bupivacaine is not currently licensed by the U.S. Food and Drug Administration for peripheral nerve block but has been approved for single-dose infiltration into the surgical site. However, it has been shown in two retrospective studies of patients with open thoracotomies for lung, pleural or mediastinal pathologies that liposomal bupivacaine intercostal nerve blockade is associated with increased pain control and decreased length of hospital stay compared to thoracic epidural analgesia.

This is a single-blind randomized prospective research study comparing pain control and postoperative outcomes following intercostal neural blockade with liposomal bupivacaine versus plain bupivacaine plus epinephrine during video-assisted thoracoscopic surgical procedures. Eligible patients would be all patients aged older than 18 years who undergo a video-assisted thoracoscopic lung resection at Massachusetts General Hospital. Pregnant women, prisoners, emergent cases, patients under 18 years, and patients with chronic pain, documented alcohol or drug abuse and allergies to bupivacaine will be excluded from this study.

Primary end point will be self-reported pain score on a visual analog scale from 0 to 10 at postoperative day #1. By utilizing a mean difference in self-reported pain scores of 1 point with a standard deviation of 2.5 points, a sample size of 100 patients per group would be needed for a power (beta) of 0.8 and probability level (alpha) of 0.05. All patients would be enrolled at Massachusetts General Hospital.

The video-assisted thoracoscopic surgeries and intercostal nerve blockade with plain bupivacaine plus epinephrine or liposomal bupivacaine will be performed by all thoracic surgeons at Massachusetts General Hospital. In the operating room after induction of general anesthesia patients will be positioned in a lateral decubitus position, prepared and draped in a sterile fashion. Under thoracoscopic guidance, a posterior intercostal nerve block will be performed with liposomal bupivacaine (13.3 mg/ml) or 0.5% bupivacaine with 1% epinephrine. In the liposomal bupivacaine group, a total dose of 266 mg of liposomal bupivacaine (one 20 ml vial of 13.3 mg/ml) per patient will be diluted to a total volume of 40 ml using 20 ml normal saline. In the bupivacaine group 20 ml of 0.5% bupivacaine with 1% epinephrine will be diluted to a total volume of 40 ml using 20 ml normal saline. From those 40 ml, 30 ml will be used for the posterior intercostal nerve block and 10 ml will be injected locally into the surgical wounds.

If immediate postoperative pain scores were rated 4/10 or greater, an intravenous patient controlled analgesia device will be provided with hydromorphone 0.2 mg every 10 minutes or nonopioid analgesics as needed. No narcotics will be given in the spinal space. Oral metoclopramide or ondansetron will be given as needed to combat the side effects of the narcotics.

Conditions

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Pain, Postoperative Thoracic Diseases Local Anesthetics Causing Adverse Effects in Therapeutic Use Opioid Dependence

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Bupivacaine

Under thoracoscopic guidance, a posterior intercostal nerve block will be performed with 0.5% bupivacaine with 1% epinephrine. In the bupivacaine group 20 ml of 0.5% bupivacaine with 1% epinephrine will be diluted to a total volume of 40 ml using 20 ml normal saline. From those 40 ml, 30 ml will be used for the posterior intercostal nerve block and 10 ml will be injected locally into the surgical wounds.

Group Type ACTIVE_COMPARATOR

Bupivacaine

Intervention Type DRUG

In the operating room after induction of general anesthesia patients will be positioned in a lateral decubitus position, prepared and draped in a sterile fashion. Under thoracoscopic guidance, a posterior intercostal nerve block will be performed with bupivacaine plus epinephrine plus normal saline.

Epinephrine

Intervention Type DRUG

In the operating room after induction of general anesthesia patients will be positioned in a lateral decubitus position, prepared and draped in a sterile fashion. Under thoracoscopic guidance, a posterior intercostal nerve block will be performed with bupivacaine plus epinephrine plus normal saline.

Normal saline

Intervention Type DRUG

In the operating room after induction of general anesthesia patients will be positioned in a lateral decubitus position, prepared and draped in a sterile fashion. Under thoracoscopic guidance, a posterior intercostal nerve block will be performed with liposomal bupivacaine plus normal saline or with bupivacaine plus epinephrine plus normal saline.

Liposomal bupivacaine

Under thoracoscopic guidance, a posterior intercostal nerve block will be performed with liposomal bupivacaine (13.3 mg/ml). In the liposomal bupivacaine group, a total dose of 266 mg of liposomal bupivacaine (one 20 ml vial of 13.3 mg/ml) per patient will be diluted to a total volume of 40 ml using 20 ml normal saline.

Group Type EXPERIMENTAL

Liposomal bupivacaine

Intervention Type DRUG

In the operating room after induction of general anesthesia patients will be positioned in a lateral decubitus position, prepared and draped in a sterile fashion. Under thoracoscopic guidance, a posterior intercostal nerve block will be performed with liposomal bupivacaine plus normal saline.

Normal saline

Intervention Type DRUG

In the operating room after induction of general anesthesia patients will be positioned in a lateral decubitus position, prepared and draped in a sterile fashion. Under thoracoscopic guidance, a posterior intercostal nerve block will be performed with liposomal bupivacaine plus normal saline or with bupivacaine plus epinephrine plus normal saline.

Interventions

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Liposomal bupivacaine

In the operating room after induction of general anesthesia patients will be positioned in a lateral decubitus position, prepared and draped in a sterile fashion. Under thoracoscopic guidance, a posterior intercostal nerve block will be performed with liposomal bupivacaine plus normal saline.

Intervention Type DRUG

Bupivacaine

In the operating room after induction of general anesthesia patients will be positioned in a lateral decubitus position, prepared and draped in a sterile fashion. Under thoracoscopic guidance, a posterior intercostal nerve block will be performed with bupivacaine plus epinephrine plus normal saline.

Intervention Type DRUG

Epinephrine

In the operating room after induction of general anesthesia patients will be positioned in a lateral decubitus position, prepared and draped in a sterile fashion. Under thoracoscopic guidance, a posterior intercostal nerve block will be performed with bupivacaine plus epinephrine plus normal saline.

Intervention Type DRUG

Normal saline

In the operating room after induction of general anesthesia patients will be positioned in a lateral decubitus position, prepared and draped in a sterile fashion. Under thoracoscopic guidance, a posterior intercostal nerve block will be performed with liposomal bupivacaine plus normal saline or with bupivacaine plus epinephrine plus normal saline.

Intervention Type DRUG

Other Intervention Names

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Exparel Marcaine Marcain Sensorcaine Vivacaine Adrenaline Adrenalin

Eligibility Criteria

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Inclusion Criteria

* Eligible patients would be all patients aged older than 18 years who undergo a video-assisted thoracoscopic lung resection at Massachusetts General Hospital.

Exclusion Criteria

* Pregnant women, prisoners, emergent cases, patients under 18 years, and patients with chronic pain, documented alcohol or drug abuse and allergies to bupivacaine will be excluded from this study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Harald Ott

Associate Professor of Surgery

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Harald Ott, MD

Role: PRINCIPAL_INVESTIGATOR

Division of Thoracic Surgery, Massachusetts General Hospital

Central Contacts

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Konstantinos P. Economopoulos, MD, PhD

Role: CONTACT

617-510-4641

Harald Ott, MD

Role: CONTACT

617-726-2311

References

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Chen AH. Toxicity and allergy to local anesthesia. J Calif Dent Assoc. 1998 Sep;26(9):683-92.

Reference Type RESULT
PMID: 9879238 (View on PubMed)

Apfelbaum JL, Chen C, Mehta SS, Gan TJ. Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 2003 Aug;97(2):534-540. doi: 10.1213/01.ANE.0000068822.10113.9E.

Reference Type RESULT
PMID: 12873949 (View on PubMed)

Luketich JD, Land SR, Sullivan EA, Alvelo-Rivera M, Ward J, Buenaventura PO, Landreneau RJ, Hart LA, Fernando HC. Thoracic epidural versus intercostal nerve catheter plus patient-controlled analgesia: a randomized study. Ann Thorac Surg. 2005 Jun;79(6):1845-9; discussion 1849-50. doi: 10.1016/j.athoracsur.2004.10.055.

Reference Type RESULT
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Oderda GM, Said Q, Evans RS, Stoddard GJ, Lloyd J, Jackson K, Rublee D, Samore MH. Opioid-related adverse drug events in surgical hospitalizations: impact on costs and length of stay. Ann Pharmacother. 2007 Mar;41(3):400-6. doi: 10.1345/aph.1H386. Epub 2007 Mar 6.

Reference Type RESULT
PMID: 17341537 (View on PubMed)

Richard BM, Rickert DE, Newton PE, Ott LR, Haan D, Brubaker AN, Cole PI, Ross PE, Rebelatto MC, Nelson KG. Safety Evaluation of EXPAREL (DepoFoam Bupivacaine) Administered by Repeated Subcutaneous Injection in Rabbits and Dogs: Species Comparison. J Drug Deliv. 2011;2011:467429. doi: 10.1155/2011/467429. Epub 2011 Oct 5.

Reference Type RESULT
PMID: 22013534 (View on PubMed)

American Society of Anesthesiologists Task Force on Acute Pain Management. 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. 2012 Feb;116(2):248-73. doi: 10.1097/ALN.0b013e31823c1030. No abstract available.

Reference Type RESULT
PMID: 22227789 (View on PubMed)

Chahar P, Cummings KC 3rd. Liposomal bupivacaine: a review of a new bupivacaine formulation. J Pain Res. 2012;5:257-64. doi: 10.2147/JPR.S27894. Epub 2012 Aug 14.

Reference Type RESULT
PMID: 23049275 (View on PubMed)

Golembiewski J, Dasta J. Evolving Role of Local Anesthetics in Managing Postsurgical Analgesia. Clin Ther. 2015 Jun 1;37(6):1354-71. doi: 10.1016/j.clinthera.2015.03.017. Epub 2015 Apr 10.

Reference Type RESULT
PMID: 25866297 (View on PubMed)

Kelly MA. Current Postoperative Pain Management Protocols Contribute to the Opioid Epidemic in the United States. Am J Orthop (Belle Mead NJ). 2015 Oct;44(10 Suppl):S5-8.

Reference Type RESULT
PMID: 26447431 (View on PubMed)

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.

Reference Type RESULT
PMID: 26507422 (View on PubMed)

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.

Reference Type RESULT
PMID: 25912739 (View on PubMed)

Uskova A, O'Connor JE. Liposomal bupivacaine for regional anesthesia. Curr Opin Anaesthesiol. 2015 Oct;28(5):593-7. doi: 10.1097/ACO.0000000000000240.

Reference Type RESULT
PMID: 26308513 (View on PubMed)

Biswas S, Verma R, Bhatia VK, Chaudhary AK, Chandra G, Prakash R. Comparison between Thoracic Epidural Block and Thoracic Paravertebral Block for Post Thoracotomy Pain Relief. J Clin Diagn Res. 2016 Sep;10(9):UC08-UC12. doi: 10.7860/JCDR/2016/19159.8489. Epub 2016 Sep 1.

Reference Type RESULT
PMID: 27790554 (View on PubMed)

Redan JA, Wells T, Reeder S, McCarus SD. Reducing Opioid Adverse Events: A Safe Way to Improve Outcomes. Surg Technol Int. 2016 Apr;28:101-9.

Reference Type RESULT
PMID: 27042786 (View on PubMed)

Clinicians' quick reference guide to postoperative pain management in adults. Pain Management Guideline Panel. Agency for Health Care Policy and Research, US Department of Health and Human Services. J Pain Symptom Manage. 1992 May;7(4):214-28.

Reference Type RESULT
PMID: 1517644 (View on PubMed)

Related Links

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http://www.hcahpsonline.org/Files/HCAHPS_Fact_Sheet_June_2015.pdf

HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) fact sheet

Other Identifiers

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2016P002754

Identifier Type: -

Identifier Source: org_study_id

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