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)
• Enrollment: 105
• Location: 1
• Arms: 2
• Actual Duration (Months): 46.7
• Patients Per Site Per Month: 2.2

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 Disease	Intervention/Treatment	Phase
Malignant Neoplasms of Female Genital Organs; Gynecologic Cancer	Drug: Bupivacaine; Drug: Liposomal Bupivacaine; Drug: Oxycodone; Behavioral: Pill Diary; Behavioral: Symptom Questionnaire	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

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: 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

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

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)

• Study Protocol and Statistical Analysis Plan - Sep 10, 2018

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by M.D. Anderson Cancer Center: Malignant neoplasms of female genital organs; Open gynecologic surgery; Local wound infiltration; Gynecologic cancer; Bupivacaine; Liposomal Bupivacaine; Oxycodone; ETH-Oxydose [DSC]; OxyContin; OxyIR; Roxicodone; Questionnaires; Surveys; MD Anderson Symptom Inventory; MDASI; Pill diary; Medication log
• Additional relevant MeSH terms: Neoplasms; Genital Neoplasms, Female; Oxycodone; Bupivacaine

Study Results

Participant Flow

Recruitment Details	All patients were consented during preoperative visit at MD Anderson Cancer Center from August 31st 2016 to August 31st 2017.
Pre-assignment Detail	One 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 Title	Active Comparator: Bupivacaine Group	Experimental: Liposomal Bupivacaine + Bupivacaine Group
Arm/Group Description	Local 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
STARTED	54	48
COMPLETED	54	48
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Active Comparator: Bupivacaine Group	Experimental: Liposomal Bupivacaine + Bupivacaine Group	Total
Arm/Group Description	Local 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 Participants	54	48	102
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

Title	Participants Opioid-Free After Gynecologic Surgery for 48 Hours
Description	Treatment arms compared with respect to the proportion of patients opioid-free at 48 hours using the Cochran-Mantel-Haenszel test stratified by surgeon.
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Comparator: Bupivacaine Group	Experimental: Liposomal Bupivacaine + Bupivacaine Group
Arm/Group Description	Local 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 Participants	54	48
Number (95% Confidence Interval) [percentage of participants]	14.8 27.4%	16.70 34.8%

2. Secondary Outcome

Title	Participants Opioid-Free After Gynecologic Surgery
Description	Treatment arms compared with respect to the number of opioid-free days using the Cochran-Mantel-Haenszel test stratified by surgeon.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Comparator: Bupivacaine Group	Experimental: Liposomal Bupivacaine + Bupivacaine Group
Arm/Group Description	Local 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 Participants	54	48
Count of Participants [Participants]	6 11.1%	8 16.7%

3. Secondary Outcome

Title	Symptom Scores
Description	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.
Time Frame	Days 0, 2 and 4 postoperatively, up to 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active Comparator: Bupivacaine Group	Experimental: Liposomal Bupivacaine + Bupivacaine Group
Arm/Group Description	Local 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 Participants	54	48
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 Frame	within 30 days of the surgery
Arm/Group Title	Active Comparator: Bupivacaine Group		Experimental: Liposomal Bupivacaine + Bupivacaine Group
Arm/Group Description	Local 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 Group		Experimental: Liposomal Bupivacaine + Bupivacaine Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/54 (0%)		0/48 (0%)
Serious Adverse Events
	Active Comparator: Bupivacaine Group		Experimental: Liposomal Bupivacaine + Bupivacaine Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/54 (0%)		0/48 (0%)
Other (Not Including Serious) Adverse Events
	Active Comparator: Bupivacaine Group		Experimental: Liposomal Bupivacaine + Bupivacaine Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/54 (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.