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

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

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.

Study Overview

• Status: Terminated
• Conditions: Gynecologic Cancer; Malignant Neoplasms of Female Genital Organs
• Intervention / Treatment: Drug: Bupivacaine; Drug: Oxycodone; Behavioral: Pill Diary; Behavioral: Symptom Questionnaire; Drug: Liposomal Bupivacaine

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 Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / 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: OxyContin; Roxicodone; OxyIR; ETH-Oxydose [DSC]; 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; MDASI; MD Anderson Symptom Inventory
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: Oxycodone; 1-2 tabs (5 mg) by mouth every 4 hours as needed for pain.; Other Names: OxyContin; Roxicodone; OxyIR; ETH-Oxydose [DSC]; 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; MDASI; MD Anderson Symptom Inventory; Drug: Liposomal Bupivacaine; 266 mg injected on each side of the wound at the end of surgery before wound closure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants Opioid-Free After Gynecologic Surgery for 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.	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants Opioid-Free After Gynecologic Surgery	Treatment arms compared with respect to the number of opioid-free days using the Cochran-Mantel-Haenszel test stratified by surgeon.	8 weeks
Symptom Scores	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.	Days 0, 2 and 4 postoperatively, up to 8 weeks

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: Pacira Pharmaceuticals, Inc
• Investigators: Principal Investigator: Pedro Ramirez, MD, M.D. Anderson Cancer Center

Publications and helpful links

General Publications

• Meyer LA, Corzo C, Iniesta MD, Munsell M, Shi Q, Pitcher B, Lasala J, Cain KE, Wang XS, Mena G, Ramirez PT. A prospective randomized trial comparing liposomal bupivacaine vs standard bupivacaine wound infiltration in open gynecologic surgery on an enhanced recovery pathway. Am J Obstet Gynecol. 2021 Jan;224(1):70.e1-70.e11. doi: 10.1016/j.ajog.2020.07.017. Epub 2020 Jul 16.

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2016
• Primary Completion (Actual): July 23, 2020
• Study Completion (Actual): July 23, 2020

Study Registration Dates

• First Submitted: April 12, 2016
• First Submitted That Met QC Criteria: April 12, 2016
• First Posted (Estimate): April 15, 2016

Study Record Updates

• Last Update Posted (Actual): October 18, 2021
• Last Update Submitted That Met QC Criteria: September 21, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Bupivacaine; Malignant neoplasms of female genital organs; Questionnaires; Surveys; Liposomal Bupivacaine; Oxycodone; Gynecologic cancer; MDASI; Open gynecologic surgery; Local wound infiltration; ETH-Oxydose [DSC]; OxyContin; OxyIR; Roxicodone; MD Anderson Symptom Inventory; Pill diary; Medication log
• Additional Relevant MeSH Terms: Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Neoplasms, Female; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Opioid; Narcotics; Anesthetics, Local; Bupivacaine; Oxycodone
• Other Study ID Numbers: 2015-1119; NCI-2016-00739 (Registry Identifier: NCI CTRP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No