Liposomal Bupivacaine for Pain Control Following Thoracic Surgery.

January 25, 2017 updated by: Harald Ott, Massachusetts General Hospital

Liposomal Bupivacaine Versus Bupivacaine for Postoperative Analgesia Following Video-assisted Thoracoscopic Surgery.

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

200

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
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.
Other Names:
  • Marcaine
  • Sensorcaine
  • Marcain
  • Vivacaine
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.
Other Names:
  • Adrenalin
  • Adrenaline
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.
Experimental: 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.
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.
Drug: 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.
Other Names:
  • Exparel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Patient self-reported pain visual analog scale score - Day 1
Time Frame: Postoperative Day #1
Postoperative Day #1

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient self-reported pain visual analog scale score - Day 3
Time Frame: Postoperative Day #3
Postoperative Day #3
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.
At the day of discharge from the hospital. Discharge day could be on average postoperative day #4 or #5.
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.
After the surgery and until the participant receives the first opioid medication, assessed up to 10 days after surgery.
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.
After the surgery and until the participant is discharged from the hospital. Discharge day could be on average postoperative day #4 or #5.
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.
After the surgery and until the participant is discharged from the hospital. Discharge day could be on average postoperative day #4 or #5.
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.
After the surgery and until the participant is discharged from the hospital. Discharge day could be on average postoperative day #4 or #5.
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.
After the surgery and until the participant is discharged from the hospital. Discharge day could be on average postoperative day #4 or #5.
Postoperative complications (e.g. pneumonia, pulmonary complications, wound infections etc)
Time Frame: The first 30 days after surgery
The first 30 days after surgery
Time to ambulation
Time Frame: After the surgery and until the participant starts ambulating during hospitalization, assessed up to 10 days after surgery.
After the surgery and until the participant starts ambulating during hospitalization, assessed up to 10 days after surgery.
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.
After the surgery and until the participant has the first bowel movement during hospitalization, assessed up to 10 days after surgery.
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.
After the surgery and until the participant has his/her chest tube removed during hospitalization, assessed up to 10 days after surgery.
Peak expiratory flow measurements
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.
Measures air flowing in and out of the lungs.
Measured twice daily following surgery until the participant is discharged from the hospital. Discharge day could be on average postoperative day #4 or #5.
Peak expiratory flow measurements
Time Frame: Measured twice daily the day at the first postoperative visit (usually within 10-30 days postoperatively)
Measures air flowing in and out of the lungs.
Measured twice daily the day at the first postoperative visit (usually within 10-30 days postoperatively)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Investigators

  • Principal Investigator: Harald Ott, MD, Division of Thoracic Surgery, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

February 1, 2017

Primary Completion (Anticipated)

December 1, 2017

Study Completion (Anticipated)

December 1, 2017

Study Registration Dates

First Submitted

December 9, 2016

First Submitted That Met QC Criteria

January 25, 2017

First Posted (Estimate)

January 30, 2017

Study Record Updates

Last Update Posted (Estimate)

January 30, 2017

Last Update Submitted That Met QC Criteria

January 25, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016P002754

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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