Wound Infiltration With Liposomal Bupivacaine vs. Standard Wound Infiltration With Bupivacaine in Patient's Undergoing Open Gynecologic Surgery on an Enhanced Recovery Pathway

Sponsor
M.D. Anderson Cancer Center (Other)
Overall Status
Terminated
CT.gov ID
NCT02740114
Collaborator
Pacira Pharmaceuticals, Inc (Industry)
105
Enrollment
1
Location
2
Arms
46.7
Actual Duration (Months)
2.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Bupivacaine is a drug that is traditionally given as an injection to numb surgical sites. Liposomes are molecules that are similar to fats. Sometimes drugs are combined with liposomes to make them able to stay in the body for longer periods of time. This has been done with bupivacaine to create liposomal bupivacaine.

The goal of this clinical research study is to compare the effects of bupivacaine to those of liposomal bupivacaine when given to patients who are having gynecologic surgery. Researchers want to compare how long the drugs work to numb the wound and how long patients take to recover from surgery.

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Detailed Description

Study Arms and Drug Administration:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study arms:

  • If you are in Arm 1, you will receive bupivacaine only.

  • If you are in Arm 2, you will receive a combination of liposomal bupivacaine and bupivacaine.

You will have an equal (50/50) chance of being assigned to either group. You will not know what you are receiving. However, the study staff will know what you are receiving.

In both cases, the drug(s) will be injected into your skin and tissue at the end of your surgery, right before the wound is closed.

Study Data Collection:

Every day while you are in the hospital recovering from surgery, you will be asked questions about pain, any side effects you may be having, symptoms, and opioid use.

Within 30 days after you leave the hospital, you may also be called and asked about side effects you may be having. If you are called, this call should last about 10-15 minutes. This information may also be collected during a routinely scheduled clinic visit and from the medical record.

Three (3) and 7 days after you leave the hospital, and then 1 time every week after that for a total of 8 weeks, you will be called or emailed and asked questions about any symptoms you may be having. If you are called, each call should last about 10-15 minutes.

If you are also enrolled on the study BS99-094 "Measuring the Symptom Distress of Cancer Patients: Development of a New Assessment System," information from your participation in this study may also be collected and used in that study.

Length of Study:

Your participation on this study will be over 8 weeks after you leave the hospital.

This is an investigational study. Both bupivacaine and liposomal bupivacaine are FDA approved and commercially available. It is investigational to compare the 2 drugs.

Up to 200 participants will be enrolled in this study. All will take part at MD Anderson.

Study Design

Study Type:
Interventional
Actual Enrollment :
105 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Primary Purpose:
Treatment
Official Title:
Wound Infiltration With Liposomal Bupivacaine vs. Standard Wound Infiltration With Bupivacaine in Patient's Undergoing Open Gynecologic Surgery on an Enhanced Recovery Pathway: A Single-Blinded, Randomized, Controlled Study
Actual Study Start Date :
Aug 31, 2016
Actual Primary Completion Date :
Jul 23, 2020
Actual Study Completion Date :
Jul 23, 2020

Arms and Interventions

ArmIntervention/Treatment
Active Comparator: Bupivacaine Group

Local wound infiltration with Bupivacaine immediately prior to wound closure during gynecological surgery. Participants discharged with analgesic opioid regimen of Oxycodone 1-2 tabs (5 mg) by mouth every 4 hours as needed for pain. Participants complete a pill diary every day for 30 days after hospital discharge. Participants called or emailed and asked questions about symptoms three (3) and 7 days after hospital discharge, and then 1 time every week after that for a total of 8 weeks.

Drug: Bupivacaine
150 mg (0.25%) injected on each side of the wound at the end of surgery before wound closure.

Drug: Oxycodone
1-2 tabs (5 mg) by mouth every 4 hours as needed for pain.
Other Names:
  • ETH-Oxydose [DSC]
  • OxyContin
  • OxyIR
  • Roxicodone
  • Behavioral: Pill Diary
    Participants complete a pill diary every day for 30 days after hospital discharge.
    Other Names:
  • Medication log
  • Behavioral: Symptom Questionnaire
    Participants called or emailed and asked questions about symptoms three (3) and 7 days after hospital discharge, and then 1 time every week after that for a total of 8 weeks.
    Other Names:
  • Survey
  • MD Anderson Symptom Inventory
  • MDASI
  • Experimental: Liposomal Bupivacaine + Bupivacaine Group

    Local wound infiltration with Liposomal Bupivacaine and 0.25% Bupivacaine admixed immediately prior to wound closure during gynecological surgery. Participants discharged with analgesic opioid regimen of Oxycodone 1-2 tabs (5 mg) by mouth every 4 hours as needed for pain. Participants complete a pill diary every day for 30 days after hospital discharge. Participants called or emailed and asked questions about symptoms three (3) and 7 days after hospital discharge, and then 1 time every week after that for a total of 8 weeks.

    Drug: Bupivacaine
    150 mg (0.25%) injected on each side of the wound at the end of surgery before wound closure.

    Drug: Liposomal Bupivacaine
    266 mg injected on each side of the wound at the end of surgery before wound closure.

    Drug: Oxycodone
    1-2 tabs (5 mg) by mouth every 4 hours as needed for pain.
    Other Names:
  • ETH-Oxydose [DSC]
  • OxyContin
  • OxyIR
  • Roxicodone
  • Behavioral: Pill Diary
    Participants complete a pill diary every day for 30 days after hospital discharge.
    Other Names:
  • Medication log
  • Behavioral: Symptom Questionnaire
    Participants called or emailed and asked questions about symptoms three (3) and 7 days after hospital discharge, and then 1 time every week after that for a total of 8 weeks.
    Other Names:
  • Survey
  • MD Anderson Symptom Inventory
  • MDASI
  • Outcome Measures

    Primary Outcome Measures

    1. Participants Opioid-Free After Gynecologic Surgery for 48 Hours [48 hours]

      Treatment arms compared with respect to the proportion of patients opioid-free at 48 hours using the Cochran-Mantel-Haenszel test stratified by surgeon.

    Secondary Outcome Measures

    1. Participants Opioid-Free After Gynecologic Surgery [8 weeks]

      Treatment arms compared with respect to the number of opioid-free days using the Cochran-Mantel-Haenszel test stratified by surgeon.

    2. Symptom Scores [Days 0, 2 and 4 postoperatively, up to 8 weeks]

      Daily pain scores were ascertained by routine nursing care every 4 hours while awake, on a 0 to 10 scale. Descriptive statistics and graphical methods used to summarize MD Anderson Symptom Inventory (MDASI) scores at each assessment time by treatment arm. For each symptom component, individuals were asked to rank symptom severity during the previous 24 hours on a scale of 0 to 10, with 0 being "not present "and 10 being "as bad as you can imagine". Symptom interference was also assessed on a 0 to 10 scale, with 0 being "did not interfere" and 10 being "interfered completely". Higher values represent worst outcomes.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Undergoing an exploratory laparotomy for suspected gynecologic cancer, which includes metastatic disease from neoplasia originating in other organs

    2. Planned participation in the Gynecologic Enhanced Recovery Pathway

    3. Female 18 years of age or older

    4. Patient must be able to read and speak English

    5. Consents to being part of a randomized, single-blinded study

    6. Patient has physical and mental capabilities to take part in study

    7. Bilirubin less than or equal to 1.5 x upper limit of the normal range (ULN); Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic-Pyruvic Transaminase (SGPT) </=2.5 x ULN

    8. If the patient is of childbearing potential, the patient must have a negative blood or urine pregnancy test within 14 days of surgical treatment on study

    Exclusion Criteria:
    1. Sensitivity to amide-type local anesthetics

    2. Patients on long-acting opioid medications, or scheduled (four or more times a day for seven or more days) short-acting opioid medications within the last 30 days

    3. Emergency surgery of any type that does not allow for proper time for protocol review by the patient

    4. Surgery that involves known/anticipated resection of anterior abdominal wall with plastic surgery reconstruction

    5. Patients undergoing pelvic exenteration

    6. Patients undergoing known/anticipated anterior abdominal wall hernia repairs

    7. Patients weighing <50 kg

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of Texas MD Anderson Cancer CenterHoustonTexasUnited States77030

    Sponsors and Collaborators

    • M.D. Anderson Cancer Center
    • Pacira Pharmaceuticals, Inc

    Investigators

    • Principal Investigator: Pedro Ramirez, MD, M.D. Anderson Cancer Center

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT02740114
    Other Study ID Numbers:
    • 2015-1119
    • NCI-2016-00739
    First Posted:
    Apr 15, 2016
    Last Update Posted:
    Oct 18, 2021
    Last Verified:
    Sep 1, 2021

    Study Results

    Participant Flow

    Recruitment DetailsAll patients were consented during preoperative visit at MD Anderson Cancer Center from August 31st 2016 to August 31st 2017.
    Pre-assignment DetailOne patient was excluded after randomization because of scheduled opioid use, and 2 patients were excluded because the surgical approach changed to minimally invasive surgery (these 3 patients were never treated). All patients treated completed the trial.
    Arm/Group TitleActive Comparator: Bupivacaine GroupExperimental: Liposomal Bupivacaine + Bupivacaine Group
    Arm/Group DescriptionLocal wound infiltration with Bupivacaine immediately prior to wound closure during gynecological surgery. Participants discharged with analgesic opioid regimen of Oxycodone 1-2 tabs (5mg) by mouth every 4 hours as needed for pain. Participants complete a pill diary every day for 30 days after hospital discharge. Participants called or emailed and asked questions about symptoms 3 and 7 days after hospital discharge, and then 1 time every week after that for a total of 8 weeks.Local wound infiltration with Liposomal Bupivacaine and 0.25% Bupivacaine admixed immediately prior to wound closure during gynecological surgery. Participants discharged with analgesic opioid regimen of Oxycodone 1-2 tabs (5 mg) by mouth every 4 hours as needed for pain. Participants complete a pill diary every day for 30 days after hospital discharge. Participants called or emailed and asked questions about symptoms 3 and 7 days after hospital discharge, and th3en 1 time every week after that for a total of 8 weeks.
    Period Title: Overall Study
    STARTED5448
    COMPLETED5448
    NOT COMPLETED00

    Baseline Characteristics

    Arm/Group TitleActive Comparator: Bupivacaine GroupExperimental: Liposomal Bupivacaine + Bupivacaine GroupTotal
    Arm/Group DescriptionLocal wound infiltration with Bupivacaine immediately prior to wound closure during gynecological surgery. Participants discharged with analgesic opioid regimen of Oxycodone 1-2 tabs (5mg) by mouth every 4 hours as needed for pain. Participants complete a pill diary every day for 30 days after hospital discharge. Participants called or emailed and asked questions about symptoms 3 and 7 days after hospital discharge, and then 1 time every week after that for a total of 8 weeks.Local wound infiltration with Liposomal Bupivacaine and 0.25% Bupivacaine admixed immediately prior to wound closure during gynecological surgery. Participants discharged with analgesic opioid regimen of Oxycodone 1-2 tabs (5 mg) by mouth every 4 hours as needed for pain. Participants complete a pill diary every day for 30 days after hospital discharge. Participants called or emailed and asked questions about symptoms 3 and 7 days after hospital discharge, and th3en 1 time every week after that for a total of 8 weeks.Total of all reporting groups
    Overall Participants5448102
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    33
    61.1%
    37
    77.1%
    70
    68.6%
    >=65 years
    21
    38.9%
    11
    22.9%
    32
    31.4%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    62.5
    59
    61
    Sex: Female, Male (Count of Participants)
    Female
    54
    100%
    48
    100%
    102
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    41
    75.9%
    37
    77.1%
    78
    76.5%
    Not Hispanic or Latino
    7
    13%
    8
    16.7%
    15
    14.7%
    Unknown or Not Reported
    6
    11.1%
    3
    6.3%
    9
    8.8%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    1.9%
    2
    4.2%
    3
    2.9%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    1
    2.1%
    1
    1%
    Black or African American
    6
    11.1%
    0
    0%
    6
    5.9%
    White
    40
    74.1%
    37
    77.1%
    77
    75.5%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    7
    13%
    8
    16.7%
    15
    14.7%
    Region of Enrollment (Count of Participants)
    United States
    54
    100%
    48
    100%
    102
    100%

    Outcome Measures

    1. Primary Outcome
    TitleParticipants Opioid-Free After Gynecologic Surgery for 48 Hours
    DescriptionTreatment arms compared with respect to the proportion of patients opioid-free at 48 hours using the Cochran-Mantel-Haenszel test stratified by surgeon.
    Time Frame48 hours

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleActive Comparator: Bupivacaine GroupExperimental: Liposomal Bupivacaine + Bupivacaine Group
    Arm/Group DescriptionLocal wound infiltration with Bupivacaine immediately prior to wound closure during gynecological surgery. Participants discharged with analgesic opioid regimen of Oxycodone 1-2 tabs (5mg) by mouth every 4 hours as needed for pain. Participants complete a pill diary every day for 30 days after hospital discharge. Participants called or emailed and asked questions about symptoms 3 and 7 days after hospital discharge, and then 1 time every week after that for a total of 8 weeks.Local wound infiltration with Liposomal Bupivacaine and 0.25% Bupivacaine admixed immediately prior to wound closure during gynecological surgery. Participants discharged with analgesic opioid regimen of Oxycodone 1-2 tabs (5 mg) by mouth every 4 hours as needed for pain. Participants complete a pill diary every day for 30 days after hospital discharge. Participants called or emailed and asked questions about symptoms 3 and 7 days after hospital discharge, and th3en 1 time every week after that for a total of 8 weeks.
    Measure Participants5448
    Number (95% Confidence Interval) [percentage of participants]
    14.8
    27.4%
    16.70
    34.8%
    2. Secondary Outcome
    TitleParticipants Opioid-Free After Gynecologic Surgery
    DescriptionTreatment arms compared with respect to the number of opioid-free days using the Cochran-Mantel-Haenszel test stratified by surgeon.
    Time Frame8 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleActive Comparator: Bupivacaine GroupExperimental: Liposomal Bupivacaine + Bupivacaine Group
    Arm/Group DescriptionLocal wound infiltration with Bupivacaine immediately prior to wound closure during gynecological surgery. Participants discharged with analgesic opioid regimen of Oxycodone 1-2 tabs (5mg) by mouth every 4 hours as needed for pain. Participants complete a pill diary every day for 30 days after hospital discharge. Participants called or emailed and asked questions about symptoms 3 and 7 days after hospital discharge, and then 1 time every week after that for a total of 8 weeks.Local wound infiltration with Liposomal Bupivacaine and 0.25% Bupivacaine admixed immediately prior to wound closure during gynecological surgery. Participants discharged with analgesic opioid regimen of Oxycodone 1-2 tabs (5 mg) by mouth every 4 hours as needed for pain. Participants complete a pill diary every day for 30 days after hospital discharge. Participants called or emailed and asked questions about symptoms 3 and 7 days after hospital discharge, and th3en 1 time every week after that for a total of 8 weeks.
    Measure Participants5448
    Count of Participants [Participants]
    6
    11.1%
    8
    16.7%
    3. Secondary Outcome
    TitleSymptom Scores
    DescriptionDaily pain scores were ascertained by routine nursing care every 4 hours while awake, on a 0 to 10 scale. Descriptive statistics and graphical methods used to summarize MD Anderson Symptom Inventory (MDASI) scores at each assessment time by treatment arm. For each symptom component, individuals were asked to rank symptom severity during the previous 24 hours on a scale of 0 to 10, with 0 being "not present "and 10 being "as bad as you can imagine". Symptom interference was also assessed on a 0 to 10 scale, with 0 being "did not interfere" and 10 being "interfered completely". Higher values represent worst outcomes.
    Time FrameDays 0, 2 and 4 postoperatively, up to 8 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleActive Comparator: Bupivacaine GroupExperimental: Liposomal Bupivacaine + Bupivacaine Group
    Arm/Group DescriptionLocal wound infiltration with Bupivacaine immediately prior to wound closure during gynecological surgery. Participants discharged with analgesic opioid regimen of Oxycodone 1-2 tabs (5mg) by mouth every 4 hours as needed for pain. Participants complete a pill diary every day for 30 days after hospital discharge. Participants called or emailed and asked questions about symptoms 3 and 7 days after hospital discharge, and then 1 time every week after that for a total of 8 weeks.Local wound infiltration with Liposomal Bupivacaine and 0.25% Bupivacaine admixed immediately prior to wound closure during gynecological surgery. Participants discharged with analgesic opioid regimen of Oxycodone 1-2 tabs (5 mg) by mouth every 4 hours as needed for pain. Participants complete a pill diary every day for 30 days after hospital discharge. Participants called or emailed and asked questions about symptoms 3 and 7 days after hospital discharge, and th3en 1 time every week after that for a total of 8 weeks.
    Measure Participants5448
    Median daily pain scores Postoperative day 0
    2.5
    2.7
    Median daily pain scores Postoperative day 2
    2.2
    2.5
    Median daily pain scores Postoperative day 4
    0.8
    1.2

    Adverse Events

    Time Framewithin 30 days of the surgery
    Adverse Event Reporting Description
    Arm/Group TitleActive Comparator: Bupivacaine GroupExperimental: Liposomal Bupivacaine + Bupivacaine Group
    Arm/Group DescriptionLocal wound infiltration with Bupivacaine immediately prior to wound closure during gynecological surgery. Participants discharged with analgesic opioid regimen of Oxycodone 1-2 tabs (5mg) by mouth every 4 hours as needed for pain. Participants complete a pill diary every day for 30 days after hospital discharge. Participants called or emailed and asked questions about symptoms 3 and 7 days after hospital discharge, and then 1 time every week after that for a total of 8 weeks.Local wound infiltration with Liposomal Bupivacaine and 0.25% Bupivacaine admixed immediately prior to wound closure during gynecological surgery. Participants discharged with analgesic opioid regimen of Oxycodone 1-2 tabs (5 mg) by mouth every 4 hours as needed for pain. Participants complete a pill diary every day for 30 days after hospital discharge. Participants called or emailed and asked questions about symptoms 3 and 7 days after hospital discharge, and th3en 1 time every week after that for a total of 8 weeks.
    All Cause Mortality
    Active Comparator: Bupivacaine GroupExperimental: Liposomal Bupivacaine + Bupivacaine Group
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/54 (0%) 0/48 (0%)
    Serious Adverse Events
    Active Comparator: Bupivacaine GroupExperimental: Liposomal Bupivacaine + Bupivacaine Group
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/54 (0%) 0/48 (0%)
    Other (Not Including Serious) Adverse Events
    Active Comparator: Bupivacaine GroupExperimental: Liposomal Bupivacaine + Bupivacaine Group
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/54 (0%) 0/48 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitlePedro Ramirez, MD /Professor, Gyn Onc & Reproductive Med
    OrganizationUT MD Anderson Cancer Center
    Phone713-745-5498
    Emailperamire@mdanderson.org
    Responsible Party:
    M.D. Anderson Cancer Center
    ClinicalTrials.gov Identifier:
    NCT02740114
    Other Study ID Numbers:
    • 2015-1119
    • NCI-2016-00739
    First Posted:
    Apr 15, 2016
    Last Update Posted:
    Oct 18, 2021
    Last Verified:
    Sep 1, 2021