Post-Mastectomy Analgesia Using Exparel (Liposomal) Versus Standard Bupivacaine or Placebo

Study Overview
=================
Brief Summary
-----------------
This is a randomized, single-blinded placebo-controlled trial. Patients will be randomized to one of three arms: (1) injection of liposomal bupivacaine at the end of the operation, (2) injection of standard bupivacaine at the end of the operation, or (3) no injection of local anesthetic. All patients will be able to receive IV and oral narcotic medications in the postoperative period on an as-needed basis. If a patient is randomized to the LB arm, at the appropriate time, under a surgeon's direction, 266 mg of (liposomal bupivacaine) LB in 20 cc of solution was expanded with various amounts of normal saline to cover the appropriate surgical field. Our routine expansion for a bilateral mastectomy is to add 80 mL of saline to 20 mL (266 mg) of LB. In our practice,we use an 18-gauge needle to inject the medication in a field-effect encompassing all 4 quadrants of the chest muscles (pectoralis and serratus) followed by injecting around the edges of the skin incision and drain site. This occurs prior to dissection of the pectoralis muscle and implant or tissue expander placement. Patients randomized to the SB arm will receive weight-based dosing of bupivacaine, administered in the same manner as the LB arm. Patients who are in the placebo arm will have a similar volume of saline injected into the operative site. Postoperatively, all patients will be kept in the hospital for at least one night. Total length of stay will be documented. They will all have the option of receiving IV morphine injections as well as oral acetaminophen-hydrocodone as needed for additional pain control. The administration of these additional medications will be recorded for each patient. On postoperative day 1, each patient will be administered the American Pain Society Outcome Questionnaire while in the hospital. After discharge from the hospital, we will call the patient on postoperative day 2, 3, 5 and 7 to assess pain and satisfaction scores, using the same questions each time. For any patients staying in the hospital longer than 1 day, the questionnaire will be administered in the hospital on the same postoperative days. Subject participation only lasts for these 7 days of follow up.

Official Title
-----------------
Single-Blinded, Randomized Assessment of Post-Mastectomy Analgesia Using Exparel (Liposomal) Versus Standard Bupivacaine or Placebo

Conditions
-----------------
Mastectomy, Breast Cancer

Intervention / Treatment
-----------------
* Drug: Liposomal bupivacaine
* Drug: Standard bupivacaine
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All female patients over 18 Subjects must be scheduled to undergo bilateral therapeutic or prophylactic skin or nipple-sparing mastectomy at Medstar Georgetown University Hospital Subjects must have immediate reconstruction consisting of either tissue expander placement or direct implant placement at the time of mastectomy subjects are capable of giving informed consent Exclusion Criteria: Subjects cannot be homeless persons Subjects cannot have active drug/alcohol dependence or abuse history. Subjects cannot be pregnant Subjects cannot have documented chronic or recent opioid use as well as chronic pain syndromes We will exclude any patients who will plan to undergo postoperative whole breast radiation Subjects cannot have bupivacaine (and all related analog) allergies

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 |
| --- | --- |
| Experimental: Liposomal bupivacaine<br>If a patient is randomized to the LB arm, at the appropriate time, under a surgeon's direction, 266 mg of (liposomal bupivacaine) LB in 20 cc of solution was expanded with various amounts of normal saline to cover the appropriate surgical field. Our routine expansion for a bilateral mastectomy is to add 80 mL of saline to 20 mL (266 mg) of LB. In our practice,we use an 18-gauge needle to inject the medication in a field-effect encompassing all 4 quadrants of the chest muscles (pectoralis and serratus) followed by injecting around the edges of the skin incision and drain site. This occurs prior to dissection of the pectoralis muscle and implant or tissue expander placement. | Drug: Liposomal bupivacaine<br>* Given at the end of the operation.<br>* Other names: Exparel;|
| Active Comparator: Standard bupivacaine<br>Patients randomized to the SB arm will receive weight-based dosing of bupivacaine, administered in the same manner as the LB arm. | Drug: Standard bupivacaine<br>* Given at the end of the operation.<br>|
| Placebo Comparator: Placebo<br>Patients who are in the placebo arm will have a similar volume of saline injected into the operative site. | Other: Placebo<br>* Saline will be administered as the placebo and will be given at the end of the operation.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postop pain and satisfaction scores | Using a validated questionnaire - the American Pain Society Outcome Questionnaire | 1 week | 
| The Number of adverse events | As measured by number by the CTCAE v4.03 | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall narcotic use | The amount of narcotics required per patient | 1 week | 
| Time in recovery | Measured as the number of hours from surgery to recovery | 1 week | 
| Time from recovery to discharge | Measured as the number of days and hours that a patient is admitted to the hospital | 1 week | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Exparel, Bupivacaine