search
Back to results

Liposomal Bupivacaine for Pain Control Following Thoracic Surgery.

Primary Purpose

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

Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Liposomal bupivacaine
Bupivacaine
Epinephrine
Normal saline
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pain, Postoperative focused on measuring postoperative pain, video-assisted thoracoscopic surgery (VATS), opioids, bupivacaine, liposomal bupivacaine, analgesia, local anesthetics

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Experimental

    Arm Label

    Bupivacaine

    Liposomal bupivacaine

    Arm Description

    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.

    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.

    Outcomes

    Primary Outcome Measures

    Patient self-reported pain visual analog scale score - Day 1

    Secondary Outcome Measures

    Patient self-reported pain visual analog scale score - Day 3
    Patient self-reported pain visual analog scale score - Discharge
    Time until first opioid usage
    Total opioid usage (in morphine equivalents)
    Anti-emetic usage
    Naloxone usage
    Length of hospital stay
    Postoperative complications (e.g. pneumonia, pulmonary complications, wound infections etc)
    Time to ambulation
    Time to first bowel movement
    Time to chest tube removal
    Peak expiratory flow measurements
    Measures air flowing in and out of the lungs.
    Peak expiratory flow measurements
    Measures air flowing in and out of the lungs.

    Full Information

    First Posted
    December 9, 2016
    Last Updated
    January 25, 2017
    Sponsor
    Massachusetts General Hospital
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT03036085
    Brief Title
    Liposomal Bupivacaine for Pain Control Following Thoracic Surgery.
    Official Title
    Liposomal Bupivacaine Versus Bupivacaine for Postoperative Analgesia Following Video-assisted Thoracoscopic Surgery.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2017
    Overall Recruitment Status
    Unknown status
    Study Start Date
    February 2017 (Anticipated)
    Primary Completion Date
    December 2017 (Anticipated)
    Study Completion Date
    December 2017 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Massachusetts General Hospital

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    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
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pain, Postoperative, Thoracic Diseases, Local Anesthetics Causing Adverse Effects in Therapeutic Use, Opioid Dependence
    Keywords
    postoperative pain, video-assisted thoracoscopic surgery (VATS), opioids, bupivacaine, liposomal bupivacaine, analgesia, local anesthetics

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2, Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    200 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Bupivacaine
    Arm Type
    Active Comparator
    Arm Description
    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.
    Arm Title
    Liposomal bupivacaine
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Liposomal bupivacaine
    Other Intervention Name(s)
    Exparel
    Intervention Description
    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
    Intervention Name(s)
    Bupivacaine
    Other Intervention Name(s)
    Marcaine, Marcain, Sensorcaine, Vivacaine
    Intervention Description
    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
    Intervention Name(s)
    Epinephrine
    Other Intervention Name(s)
    Adrenaline, Adrenalin
    Intervention Description
    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
    Intervention Name(s)
    Normal saline
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Patient self-reported pain visual analog scale score - Day 1
    Time Frame
    Postoperative Day #1
    Secondary Outcome Measure Information:
    Title
    Patient self-reported pain visual analog scale score - Day 3
    Time Frame
    Postoperative Day #3
    Title
    Patient self-reported pain visual analog scale score - Discharge
    Time Frame
    At the day of discharge from the hospital. Discharge day could be on average postoperative day #4 or #5.
    Title
    Time until first opioid usage
    Time Frame
    After the surgery and until the participant receives the first opioid medication, assessed up to 10 days after surgery.
    Title
    Total opioid usage (in morphine equivalents)
    Time Frame
    After the surgery and until the participant is discharged from the hospital. Discharge day could be on average postoperative day #4 or #5.
    Title
    Anti-emetic usage
    Time Frame
    After the surgery and until the participant is discharged from the hospital. Discharge day could be on average postoperative day #4 or #5.
    Title
    Naloxone usage
    Time Frame
    After the surgery and until the participant is discharged from the hospital. Discharge day could be on average postoperative day #4 or #5.
    Title
    Length of hospital stay
    Time Frame
    After the surgery and until the participant is discharged from the hospital. Discharge day could be on average postoperative day #4 or #5.
    Title
    Postoperative complications (e.g. pneumonia, pulmonary complications, wound infections etc)
    Time Frame
    The first 30 days after surgery
    Title
    Time to ambulation
    Time Frame
    After the surgery and until the participant starts ambulating during hospitalization, assessed up to 10 days after surgery.
    Title
    Time to first bowel movement
    Time Frame
    After the surgery and until the participant has the first bowel movement during hospitalization, assessed up to 10 days after surgery.
    Title
    Time to chest tube removal
    Time Frame
    After the surgery and until the participant has his/her chest tube removed during hospitalization, assessed up to 10 days after surgery.
    Title
    Peak expiratory flow measurements
    Description
    Measures air flowing in and out of the lungs.
    Time Frame
    Measured twice daily following surgery until the participant is discharged from the hospital. Discharge day could be on average postoperative day #4 or #5.
    Title
    Peak expiratory flow measurements
    Description
    Measures air flowing in and out of the lungs.
    Time Frame
    Measured twice daily the day at the first postoperative visit (usually within 10-30 days postoperatively)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Konstantinos P. Economopoulos, MD, PhD
    Phone
    617-510-4641
    Email
    keconomopoulos@mgh.harvard.edu
    First Name & Middle Initial & Last Name or Official Title & Degree
    Harald Ott, MD
    Phone
    617-726-2311
    Email
    hott@mgh.harvard.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Harald Ott, MD
    Organizational Affiliation
    Division of Thoracic Surgery, Massachusetts General Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    9879238
    Citation
    Chen AH. Toxicity and allergy to local anesthesia. J Calif Dent Assoc. 1998 Sep;26(9):683-92.
    Results Reference
    result
    PubMed Identifier
    12873949
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    15919269
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    17341537
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    22013534
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    22227789
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    23049275
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    25866297
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    26447431
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    26507422
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    25912739
    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.
    Results Reference
    result
    PubMed Identifier
    26308513
    Citation
    Uskova A, O'Connor JE. Liposomal bupivacaine for regional anesthesia. Curr Opin Anaesthesiol. 2015 Oct;28(5):593-7. doi: 10.1097/ACO.0000000000000240.
    Results Reference
    result
    PubMed Identifier
    27790554
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    27042786
    Citation
    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.
    Results Reference
    result
    PubMed Identifier
    1517644
    Citation
    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.
    Results Reference
    result
    Links:
    URL
    http://www.hcahpsonline.org/Files/HCAHPS_Fact_Sheet_June_2015.pdf
    Description
    HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) fact sheet
    URL
    http://www.exparel.com/hcp/pdf/EXPAREL_Prescribing_Information.pdf
    Description
    Exparel prescribing information

    Learn more about this trial

    Liposomal Bupivacaine for Pain Control Following Thoracic Surgery.

    We'll reach out to this number within 24 hrs