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

Pain, Postoperative Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02352922
• Other study ID #: 691275
• Status: Completed
• Phase: Phase 4
• Start date: July 2015
• Est. completion date: February 2016

Study information

• Verified date: September 2020
• Source: AdventHealth
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: February 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Benign indication for surgery

2. Planned multiport laparoscopic or robotic assisted hysterectomy

3. Non-pregnant

4. Able to provide informed consent

5. Owns smartphone or computer with internet access

6. Willing to provide contact phone number and accept SMS text messages

7. Ability to speak and read English (because texts and online surveys will be in English only)

Exclusion Criteria:

1. Planned additional procedures (e.g. incontinence surgery, prolapse repair or bowel surgery)

2. Contraindication to study drug

1. Severe Hepatic disease

2. Severe Kidney disease

3. Current use of monoamine oxidase inhibitors

4. Current use of tricyclic antidepressants

3. History of substance or alcohol abuse within the past 2 years

Related Conditions & MeSH terms

• Pain, Postoperative
• Surgical Procedure, Unspecified

Intervention

Drug:
• Liposomal Bupivacaine
pre-incision infiltration with liposomal bupivacaine
• Bupivacaine HCl
pre-incision infiltration with bupivacaine HCl

Locations

Country	Name	City	State
United States	Florida Hospital Orlando	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AdventHealth

Country where clinical trial is conducted

United States, 

References & Publications (8)

Bergese SD, Onel E, Portillo J. Evaluation of DepoFoam(®) bupivacaine for the treatment of postsurgical pain. Pain Manag. 2011 Nov;1(6):539-47. doi: 10.2217/pmt.11.62. — View Citation

Bramlett K, Onel E, Viscusi ER, Jones K. A randomized, double-blind, dose-ranging study comparing wound infiltration of DepoFoam bupivacaine, an extended-release liposomal bupivacaine, to bupivacaine HCl for postsurgical analgesia in total knee arthroplasty. Knee. 2012 Oct;19(5):530-6. doi: 10.1016/j.knee.2011.12.004. Epub 2012 Jan 28. — View Citation

Golf M, Daniels SE, Onel E. A phase 3, randomized, placebo-controlled trial of DepoFoam® bupivacaine (extended-release bupivacaine local analgesic) in bunionectomy. Adv Ther. 2011 Sep;28(9):776-88. doi: 10.1007/s12325-011-0052-y. Epub 2011 Aug 12. — View Citation

Gorfine SR, Onel E, Patou G, Krivokapic ZV. Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double-blind, placebo-controlled trial. Dis Colon Rectum. 2011 Dec;54(12):1552-9. doi: 10.1097/DCR.0b013e318232d4c1. — View Citation

Kato J, Ogawa S, Katz J, Nagai H, Kashiwazaki M, Saeki H, Suzuki H. Effects of presurgical local infiltration of bupivacaine in the surgical field on postsurgical wound pain in laparoscopic gynecologic examinations: a possible preemptive analgesic effect. Clin J Pain. 2000 Mar;16(1):12-7. — View Citation

Ke RW, Portera SG, Bagous W, Lincoln SR. A randomized, double-blinded trial of preemptive analgesia in laparoscopy. Obstet Gynecol. 1998 Dec;92(6):972-5. — View Citation

Loizides S, Gurusamy KS, Nagendran M, Rossi M, Guerrini GP, Davidson BR. Wound infiltration with local anaesthetic agents for laparoscopic cholecystectomy. Cochrane Database Syst Rev. 2014 Mar 12;(3):CD007049. doi: 10.1002/14651858.CD007049.pub2. Review. — View Citation

Saleh A, Fox G, Felemban A, Guerra C, Tulandi T. Effects of local bupivacaine instillation on pain after laparoscopy. J Am Assoc Gynecol Laparosc. 2001 May;8(2):203-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	NRS Pain Score at 8 Hours	Pain scale (0-10), where 0 = no pain and 10 = worst pain imaginable	8 hours post-op
Secondary	NRS Pain Score at 16 Hours	Pain scale (0-10), where 0 = no pain and 10 = worst pain imaginable	16 hours post-op
Secondary	NRS Pain Score Post-op Day 2	Pain scale (0-10), where 0 = no pain and 10 = worst pain imaginable	2 days post-op
Secondary	NRS Pain Score Post-op Day 3	Pain scale, where 0 = no pain and 10 = worst pain imaginable	3 days post-op
Secondary	NRS Pain Score Post-op Day 14	Pain scale (0-10), where 0 = no pain and 10 = worst pain imaginable	Post-Operative Day 14
Secondary	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
Secondary	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
Secondary	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
Secondary	Total Opioid Use Prior to Hospital Discharge	Oral morphine equivalent of opioid use while in the hospital	24 hours
Secondary	Total Opioid Use End of Post-op Day 3	Total use of home opioids by pill count/ oral morphine equivalents	72 hrs post-op
Secondary	Total Opioid Use at Post-op Day 14	Total use of home opioids by pill count/ oral morphine equivalents	Post-Operative Day 14
Secondary	Number of Participants With Adverse Events		Post-Operative Day 14