Liposomal Bupivacaine in Implant Based Breast Reconstruction

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ClinicalTrials.gov Identifier: NCT02659501

Recruitment Status : Terminated

First Posted : January 20, 2016

Results First Posted : August 21, 2019

Last Update Posted : January 12, 2021

Sponsor:

Information provided by (Responsible Party):

Subhas Gupta, MD, PhD, Loma Linda University

Study Description

Brief Summary:

Objectives:

To evaluate the effect of liposomal bupivacaine on postoperative pain levels.
To evaluate the effect of liposomal bupivacaine on postoperative opioid consumption and opioid related adverse events.
To evaluate the effect of liposomal bupivacaine on length of hospital stay.
To evaluate the effect of liposomal bupivacaine on patient satisfaction with postoperative pain control.
To evaluate the effect of liposomal bupivacaine on overall patient satisfaction.

Condition or disease	Intervention/treatment	Phase
Breast Cancer Postoperative Pain	Drug: Liposomal bupivacaine Drug: Bupivacaine with epinephrine Drug: Morphine sulfate Drug: Hydrocodone/acetaminophen Drug: Diazepam	Not Applicable

Detailed Description:

Objectives:

To evaluate the effect of liposomal bupivacaine on postoperative pain levels.
To evaluate the effect of liposomal bupivacaine on postoperative opioid consumption and opioid related adverse events.
To evaluate the effect of liposomal bupivacaine on length of hospital stay.
To evaluate the effect of liposomal bupivacaine on patient satisfaction with postoperative pain control.
To evaluate the effect of liposomal bupivacaine on overall patient satisfaction.

The objective of this project is to evaluate the role of liposomal bupivacaine in postoperative pain control following tissue expander and implant based breast reconstruction. This unique formulation of bupivacaine lends this drug a longer duration of action and reduced plasma bupivacaine concentrations compared to plain bupivacaine. This agent has been demonstrated to be safe, well tolerated, and effective in a number of different clinical applications. However, its role has yet to be evaluated in the context of breast reconstruction.

Thus, the authors propose the first, randomized, controlled clinical trial of liposomal bupivacaine for postoperative pain management following tissue expander and implant based breast reconstruction. Patients will be stratified into two study groups. Patients in the Group 1 (Bupivacaine) will be treated intraoperatively with injections of 0.5% bupivacaine and epinephrine 1:200,000, with 50 mg delivered to perform a field block of each pocket. This is the current standard of care. Patients in the Group 2 (Liposomal Bupivacaine) will be treated intraoperatively with injections of 1.33% liposomal bupivacaine, with 133 mg delivered to perform a field block of each breast pocket. This is the experimental intervention. Postoperatively, the investigators will assess pain levels, opioid consumption, opioid related adverse events, length of stay, and satisfaction.

The findings from this study will allow the authors to better elucidate the role of liposomal bupivacaine in expander/implant based breast reconstruction. In doing so, they may allow the authors to identify the ideal pain regimen for these patients. This holds important implications, with the potential to reduce postoperative pain, opioid consumption, opioid related adverse events, length of stay, and patient satisfaction.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	24 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Participant)
Primary Purpose:	Treatment
Official Title:	Liposomal Bupivacaine in Implant Based Breast Reconstruction
Actual Study Start Date :	July 2015
Actual Primary Completion Date :	September 2016
Actual Study Completion Date :	July 2017

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Breast cancer

MedlinePlus related topics: Breast Reconstruction Plastic and Cosmetic Surgery

Drug Information available for: Bupivacaine hydrochloride Bupivacaine

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Bupivacaine with epinephrine injections Patients in the control arm of the study will be treated intra-operatively with standard of care, 0.5% bupivacaine and epinephrine injection (1:200,000), with 50 mg delivered into each breast pocket to perform a field block of the breast pocket (see below). Postoperatively, these patients will be treated with standard postoperative pain control, including narcotics as needed, such as morphine sulfate and hydrocodone/acetaminophen, and muscle relaxants, such as diazepam.	Drug: Bupivacaine with epinephrine Bupivacaine, like other local anesthetics reduces the flow of sodium in and out of nerves. This decreases the initiation and transfer of nerve signals in the area in which the drug is injected. This leads first to a loss of sensation of pain, temperature, touch, and deep pressure. This drug is the current standard of care for local, postoperative local anesthesia following breast reconstruction. Epinephrine, a vasoconstrictor, is included in bupivacaine formulations to improve the duration of local anesthesia. Other Names: Marcaine Sensorcaine Drug: Morphine sulfate Morphine is an opiate pain medication administered intravenously for severe, breakthrough post-operative pain. Other Name: Roxanol Drug: Hydrocodone/acetaminophen Hydrocodone acetaminophen is a combination of an opiate pain medication (hydrocodone) and a non-steroidal anti-inflammatory drug (acetaminophen) given orally to patients for moderate post-operative pain. Other Name: Norco Drug: Diazepam Diazepam is a benzodiazepine medication that is administered orally to treat muscle spasms in patient's following expander and implant-based breast reconstruction. Other Name: Valium
Experimental: Liposomal bupivacaine Patients in the experimental arm of the study will be treated intra-operatively with 1.33% liposomal bupivacaine, with 133 mg delivered to perform a field block of each breast pocket. Postoperatively, these patients will be treated with standard postoperative pain control, including narcotics as needed, such as morphine sulfate and hydrocodone/acetaminophen, and muscle relaxants, such as diazepam.	Drug: Liposomal bupivacaine Liposomal Bupivacaine is an aqueous suspension of multivesicular liposomes containing bupivacaine. After injection into soft tissue, bupivacaine is slowly released from the multivesicular liposomes, extending this drug's duration of action. Other Name: Exparel Drug: Morphine sulfate Morphine is an opiate pain medication administered intravenously for severe, breakthrough post-operative pain. Other Name: Roxanol Drug: Hydrocodone/acetaminophen Hydrocodone acetaminophen is a combination of an opiate pain medication (hydrocodone) and a non-steroidal anti-inflammatory drug (acetaminophen) given orally to patients for moderate post-operative pain. Other Name: Norco Drug: Diazepam Diazepam is a benzodiazepine medication that is administered orally to treat muscle spasms in patient's following expander and implant-based breast reconstruction. Other Name: Valium

Arm

Intervention/treatment

Active Comparator: Bupivacaine with epinephrine injections

Patients in the control arm of the study will be treated intra-operatively with standard of care, 0.5% bupivacaine and epinephrine injection (1:200,000), with 50 mg delivered into each breast pocket to perform a field block of the breast pocket (see below). Postoperatively, these patients will be treated with standard postoperative pain control, including narcotics as needed, such as morphine sulfate and hydrocodone/acetaminophen, and muscle relaxants, such as diazepam.

Drug: Bupivacaine with epinephrine

Bupivacaine, like other local anesthetics reduces the flow of sodium in and out of nerves. This decreases the initiation and transfer of nerve signals in the area in which the drug is injected. This leads first to a loss of sensation of pain, temperature, touch, and deep pressure. This drug is the current standard of care for local, postoperative local anesthesia following breast reconstruction. Epinephrine, a vasoconstrictor, is included in bupivacaine formulations to improve the duration of local anesthesia.

Other Names:

Marcaine
Sensorcaine

Drug: Morphine sulfate

Morphine is an opiate pain medication administered intravenously for severe, breakthrough post-operative pain.

Other Name: Roxanol

Drug: Hydrocodone/acetaminophen

Hydrocodone acetaminophen is a combination of an opiate pain medication (hydrocodone) and a non-steroidal anti-inflammatory drug (acetaminophen) given orally to patients for moderate post-operative pain.

Other Name: Norco

Drug: Diazepam

Diazepam is a benzodiazepine medication that is administered orally to treat muscle spasms in patient's following expander and implant-based breast reconstruction.

Other Name: Valium

Experimental: Liposomal bupivacaine

Patients in the experimental arm of the study will be treated intra-operatively with 1.33% liposomal bupivacaine, with 133 mg delivered to perform a field block of each breast pocket. Postoperatively, these patients will be treated with standard postoperative pain control, including narcotics as needed, such as morphine sulfate and hydrocodone/acetaminophen, and muscle relaxants, such as diazepam.

Drug: Liposomal bupivacaine

Liposomal Bupivacaine is an aqueous suspension of multivesicular liposomes containing bupivacaine. After injection into soft tissue, bupivacaine is slowly released from the multivesicular liposomes, extending this drug's duration of action.

Other Name: Exparel

Drug: Morphine sulfate

Morphine is an opiate pain medication administered intravenously for severe, breakthrough post-operative pain.

Other Name: Roxanol

Drug: Hydrocodone/acetaminophen

Other Name: Norco

Drug: Diazepam

Diazepam is a benzodiazepine medication that is administered orally to treat muscle spasms in patient's following expander and implant-based breast reconstruction.

Other Name: Valium

Outcome Measures

Primary Outcome Measures :

The Effect of Liposomal Bupivacaine on Average Postoperative Pain Levels on Postoperative Day 1. [ Time Frame: Average Pain Scores 24 hours Post-Operatively ]
Postoperative pain levels were determined with a numeric rating scale (NRS), rating pain from 0 - 10, where 0 = no pain, 10 = worst possible pain. Higher scores indicate a worse outcome. Pain levels were determined during routine vital signs every 4 hours post-operatively.
The Effect of Liposomal Bupivacaine on Antiemetic Consumption [ Time Frame: 24 hours ]
The effect of liposomal bupivacaine on antiemetic consumption was assessed in mg of ondansetron consumed over first 24 hours post-operatively.
The Effect of Liposomal Bupivacaine on Postoperative Opioid Consumption [ Time Frame: 24 hours ]
Postoperative opioid consumption will be determined in each group. Opioid consumption post-operatively will be determined for patients in each group in standardized units of morphine milligram dosing equivalents per hour.
The Effect of Liposomal Bupivacaine on Postoperative Diazepam Consumption [ Time Frame: 24 hours ]
Benzodiazepine consumption, in mg of diazepam, was recorded for all patients and compared over the first 24 hours post-operatively.
The Effect of Liposomal Bupivacaine on Length of Hospital Stay [ Time Frame: 24-60 hours ]
Length of hospital stay will be determined for patients in each group, in total hours.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 99 Years (Adult, Older Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Women undergoing immediate unilateral or bilateral tissue-expander breast reconstruction following skin-sparing or nipple-sparing mastectomy

Exclusion Criteria:

Women who are unable to give informed consent to participate in this study
Women with a documented history of hypersensitivity reactions to local-anesthetic agents
Women with a diagnosis of chronic pain disorders such as fibromyalgia, chronic migraine headaches, or psychiatric disorders other than depression or anxiety
Women who are currently pregnant
Women undergoing tissue expander based breast reconstruction with a muscle flap in combination with a tissue expander
Women with impaired hepatic function

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02659501

Locations

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United States, California
Loma Linda University Health System
Loma Linda, California, United States, 92354

Sponsors and Collaborators

Loma Linda University

Investigators

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Principal Investigator:	Subhas C. Gupta, MD, PhD	Loma Linda University
Study Director:	Wendy W. Wong, MD	Loma Linda University

More Information

Publications:

Heller L, Kowalski AM, Wei C, Butler CE. Prospective, randomized, double-blind trial of local anesthetic infusion and intravenous narcotic patient-controlled anesthesia pump for pain management after free TRAM flap breast reconstruction. Plast Reconstr Surg. 2008 Oct;122(4):1010-8. doi: 10.1097/PRS.0b013e3181858c09.

Wheble GA, Tan EK, Turner M, Durrant CA, Heppell S. Surgeon-administered, intra-operative transversus abdominis plane block in autologous breast reconstruction: a UK hospital experience. J Plast Reconstr Aesthet Surg. 2013 Dec;66(12):1665-70. doi: 10.1016/j.bjps.2013.07.017. Epub 2013 Jul 31.

Dasta J, Ramamoorthy S, Patou G, Sinatra R. Bupivacaine liposome injectable suspension compared with bupivacaine HCl for the reduction of opioid burden in the postsurgical setting. Curr Med Res Opin. 2012 Oct;28(10):1609-15. doi: 10.1185/03007995.2012.721760. Epub 2012 Sep 3.

Richard BM, Ott LR, Haan D, Brubaker AN, Cole PI, Nelson KG, Ross PE, Rebelatto MC, Newton PE. The safety and tolerability evaluation of DepoFoam bupivacaine (bupivacaine extended-release liposome injection) administered by incision wound infiltration in rabbits and dogs. Expert Opin Investig Drugs. 2011 Oct;20(10):1327-41. doi: 10.1517/13543784.2011.611499. Epub 2011 Aug 26.

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.

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Responsible Party:	Subhas Gupta, MD, PhD, Principal Investigator, Loma Linda University
ClinicalTrials.gov Identifier:	NCT02659501
Other Study ID Numbers:	5150012
First Posted:	January 20, 2016 Key Record Dates
Results First Posted:	August 21, 2019
Last Update Posted:	January 12, 2021
Last Verified:	December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Subhas Gupta, MD, PhD, Loma Linda University:


Breast reconstruction Bupivacaine Liposomal bupivacaine Postoperative analgesia

Additional relevant MeSH terms:

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Pain, Postoperative Postoperative Complications Pathologic Processes Pain Neurologic Manifestations Acetaminophen Acetaminophen, hydrocodone drug combination Epinephrine Diazepam Morphine Hydrocodone Bupivacaine Anesthetics, Local Anesthetics Central Nervous System Depressants	Physiological Effects of Drugs Sensory System Agents Peripheral Nervous System Agents Analgesics, Opioid Narcotics Analgesics Analgesics, Non-Narcotic Antipyretics Adrenergic alpha-Agonists Adrenergic Agonists Adrenergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Adrenergic beta-Agonists Bronchodilator Agents

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