Randomized Trial of Wound Infiltration With Extended-release Bupivacaine Before Laparoscopic or Robotic Hysterectomy

Study Overview
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Brief Summary
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The investigators are studying ways to improve pain control after surgery. One way to decrease pain is to inject incisions with a numbing medicine (local anesthetic) while in the operating room. There is an FDA approved extended-release version of a commonly used local anesthetic (bupivacaine) that can last for 4 days instead of 6 hours. The investigators are studying whether using the extended-release medication (Exparel) will give better pain relief after laparoscopic and robotic-assisted hysterectomies.

Detailed Description
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Lidocaine and bupivacaine hydrochloride (HCl) are the most commonly used drugs for wound infiltration during laparoscopic surgery for post-operative pain control. There is some evidence that wound infiltration decreases immediate post-operative pain. While bupivacaine has a slightly slower onset of action (5-10 minutes), it has become the preferred injectable anesthetic for surgical use because of its longer duration of effect (4-8 hours versus 1-2 hours for lidocaine). DepoFoam bupivacaine (EXPAREL, Pacira Pharmaceuticals, Inc., Parsippany, NJ, USA) is a newer extended-release formulation of bupivacaine HCl approved by the U.S. Federal Drug Administration in October 2011. In this suspension, bupivacaine is encapsulated in microscopic spherical lipid-based particles of varying size to allow dispersion of the drug over an extended period of time. Analgesia is prolonged up to 96 hours. Given the extended duration of action, this liposomal bupivacaine may be better at providing post-operative pain relief in laparoscopic surgery. Phase three trials have shown better pain control in the first 24 hours and less opioid use overall in bunionectomies, hemorrhoidectomies, and total knee replacement surgery when compared to placebo. No studies, however, have been published evaluating extended-release liposomal bupivacaine for laparoscopic surgery, or gynecologic surgery in general. Currently, we are using liposomal bupivacaine for pain relief after laparoscopic hysterectomies, but as stated, it has never been formally evaluated. We hypothesize that liposomal bupivacaine (extended-release) provides extended pain relief and decreases the need for supplemental opioid use after major laparoscopic surgery. We will be evaluating whether pre-incision infiltration of extended-release bupivacaine decreases post-operative pain from laparoscopic and robotic-assisted hysterectomy compared to bupivacaine HCl (short-acting). To achieve this evaluation we designed a double-blinded randomized controlled trial. Patients who are scheduled to undergo a laparoscopic or robotic-assisted hysterectomy will be invited to participate. Group A will receive pre-incision infiltration of each trocar site with 4 ml of 0.25% Bupivacaine HCl. Group B will receive pre-incision infiltration of each trocar site with 4 ml of extended-release bupivacaine (EXPAREL) (13.3mg/ml). Subjects and outcome assessors will be blinded to group allocation. Data will be collected while patients are in the hospital on pain levels and consumption of opioid pain medications. Upon discharge, pain levels, functioning, and quantity of opioid and non-steroidal anti-inflammatory (NSAID) pain medications will be collected through online questionnaires. Subjects will be followed until their 2-3 weeks post-operative visit.

Official Title
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A Randomized Controlled Trial of Wound Infiltration With Extended-release Versus Short-acting Bupivacaine Before Laparoscopic or Robotic Hysterectomy

Conditions
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Pain, Postoperative, Surgical Procedure, Unspecified

Intervention / Treatment
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* Drug: Liposomal Bupivacaine
* Drug: Bupivacaine HCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Benign indication for surgery Planned multiport laparoscopic or robotic assisted hysterectomy Non-pregnant Able to provide informed consent Owns smartphone or computer with internet access Willing to provide contact phone number and accept SMS text messages Ability to speak and read English (because texts and online surveys will be in English only) Exclusion Criteria: Planned additional procedures (e.g. incontinence surgery, prolapse repair or bowel surgery) Contraindication to study drug Severe Hepatic disease Severe Kidney disease Current use of monoamine oxidase inhibitors Current use of tricyclic antidepressants History of substance or alcohol abuse within the past 2 years

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liposomal Bupivacaine<br>extended-release bupivacaine (EXPAREL) | Drug: Liposomal Bupivacaine<br>* pre-incision infiltration with liposomal bupivacaine<br>* Other names: Exparel;|
| Active Comparator: Bupivacaine HCl<br>short-acting bupivacaine | Drug: Bupivacaine HCl<br>* pre-incision infiltration with bupivacaine HCl<br>* Other names: Marcaine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numerical Rating Scale (NRS) Post-operative Pain Score on Post-Operative Day 1 (POD1). | Numerical Rating Scale (0-10) post-operative pain score on POD1, where 0 = no pain and 10 = worst pain imaginable | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NRS Pain Score at 2 Hours | numeric rating scale (0-10), mean and SD, where 0 = no pain and 10 = worst pain imaginable | 2 hours post-op | 
| NRS Pain Score at 4 Hours | Pain scale measured from 0-10, where 0 = no pain and 10 = worst pain imaginable | 4 hours post-op | 
| NRS Pain Score at 8 Hours | Pain scale (0-10), where 0 = no pain and 10 = worst pain imaginable | 8 hours post-op | 
| NRS Pain Score at 16 Hours | Pain scale (0-10), where 0 = no pain and 10 = worst pain imaginable | 16 hours post-op | 
| NRS Pain Score Post-op Day 2 | Pain scale (0-10), where 0 = no pain and 10 = worst pain imaginable | 2 days post-op | 
| NRS Pain Score Post-op Day 3 | Pain scale, where 0 = no pain and 10 = worst pain imaginable | 3 days post-op | 
| NRS Pain Score Post-op Day 14 | Pain scale (0-10), where 0 = no pain and 10 = worst pain imaginable | Post-Operative Day 14 | 
| Quality of Life as Measured by the Brief Pain Inventory (BPI) | The brief pain inventory scale uses the 0 to 10 numerical rating scale to measure pain intensity under four different conditions. On the four conditions 0 = no pain, no relief, and does not interfere, whereas 10 = pain as bad as you can imagine, complete relief, and completely interferes | Post-Operative Day 2 | 
| Quality of Life as Measured by the Brief Pain Inventory (BPI) | The brief pain inventory scale uses the 0 to 10 numerical rating scale to measure pain intensity under four different conditions. On the four conditions 0 = no pain, no relief, and does not interfere, whereas 10 = pain as bad as you can imagine, complete relief, and completely interferes | Post-Operative Day 3 | 
| Quality of Life as Measured by the Brief Pain Inventory (BPI) | at time of post-op visit The brief pain inventory scale uses the 0 to 10 numerical rating scale to measure pain intensity under four different conditions. On the four conditions 0 = no pain, no relief, and does not interfere, whereas 10 = pain as bad as you can imagine, complete relief, and completely interferes | Post-Operative Day 14 | 
| Total Opioid Use Prior to Hospital Discharge | Oral morphine equivalent of opioid use while in the hospital | 24 hours | 
| Total Opioid Use End of Post-op Day 3 | Total use of home opioids by pill count/ oral morphine equivalents | 72 hrs post-op | 
| Total Opioid Use at Post-op Day 14 | Total use of home opioids by pill count/ oral morphine equivalents | Post-Operative Day 14 | 
| Number of Participants With Adverse Events |  | Post-Operative Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Laparoscopy, Robotic Surgical Procedures, Hysterectomy, Anesthetics, Local, Bupivacaine, Pain, Postoperative