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

Study Overview
=================
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.

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.

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

Conditions
-----------------
Malignant Neoplasms of Female Genital Organs, Gynecologic Cancer

Intervention / Treatment
-----------------
* Drug: Bupivacaine
* Drug: Liposomal Bupivacaine
* Drug: Oxycodone
* Behavioral: Pill Diary
* Behavioral: Symptom Questionnaire


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Undergoing an exploratory laparotomy for suspected gynecologic cancer, which includes metastatic disease from neoplasia originating in other organs Planned participation in the Gynecologic Enhanced Recovery Pathway Female 18 years of age or older Patient must be able to read and speak English Consents to being part of a randomized, single-blinded study Patient has physical and mental capabilities to take part in study 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 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: Sensitivity to amide-type local anesthetics 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 Emergency surgery of any type that does not allow for proper time for protocol review by the patient Surgery that involves known/anticipated resection of anterior abdominal wall with plastic surgery reconstruction Patients undergoing pelvic exenteration Patients undergoing known/anticipated anterior abdominal wall hernia repairs Patients weighing <50 kg

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bupivacaine Group<br>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<br>* 150 mg (0.25%) injected on each side of the wound at the end of surgery before wound closure.<br>Drug: Oxycodone<br>* 1-2 tabs (5 mg) by mouth every 4 hours as needed for pain.<br>* Other names: Roxicodone;Behavioral: Pill Diary<br>* Participants complete a pill diary every day for 30 days after hospital discharge.<br>* Other names: Medication log;Behavioral: Symptom Questionnaire<br>* 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.<br>* Other names: MDASI;|
| Experimental: Liposomal Bupivacaine + Bupivacaine Group<br>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<br>* 150 mg (0.25%) injected on each side of the wound at the end of surgery before wound closure.<br>Drug: Liposomal Bupivacaine<br>* 266 mg injected on each side of the wound at the end of surgery before wound closure.<br>Drug: Oxycodone<br>* 1-2 tabs (5 mg) by mouth every 4 hours as needed for pain.<br>* Other names: Roxicodone;Behavioral: Pill Diary<br>* Participants complete a pill diary every day for 30 days after hospital discharge.<br>* Other names: Medication log;Behavioral: Symptom Questionnaire<br>* 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.<br>* Other names: MDASI;|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Surveys, 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, MD Anderson Symptom Inventory, MDASI, Pill diary, Medication log