Clinical trial NCT02352922: Randomized Trial of Wound Infiltration With Extended-release Bupivacaine Before Laparoscopic or Robotic Hysterectomy
Official title: A Randomized Controlled Trial of Wound Infiltration With Extended-release Versus Short-acting Bupivacaine Before Laparoscopic or Robotic Hysterectomy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pain, Postoperative
Surgical Procedure, Unspecified
Keywords: Laparoscopy
Robotic Surgical Procedures
Hysterectomy
Anesthetics, Local
Bupivacaine
Pain, Postoperative
Lead sponsor: AdventHealth
Sponsor class: OTHER
First posted: 2015-02-02
Enrollment: 64
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Numerical Rating Scale (NRS) Post-operative Pain Score on Post-Operative Day 1 (POD1).
timeFrame: 24 hours
Secondary outcomes:
measure: NRS Pain Score at 2 Hours
timeFrame: 2 hours post-op
measure: NRS Pain Score at 4 Hours
timeFrame: 4 hours post-op
measure: NRS Pain Score at 8 Hours
timeFrame: 8 hours post-op
measure: NRS Pain Score at 16 Hours
timeFrame: 16 hours post-op
measure: NRS Pain Score Post-op Day 2
timeFrame: 2 days post-op
measure: NRS Pain Score Post-op Day 3
timeFrame: 3 days post-op
measure: NRS Pain Score Post-op Day 14
timeFrame: Post-Operative Day 14
measure: Quality of Life as Measured by the Brief Pain Inventory (BPI)
timeFrame: Post-Operative Day 2
measure: Quality of Life as Measured by the Brief Pain Inventory (BPI)
timeFrame: Post-Operative Day 3
measure: Quality of Life as Measured by the Brief Pain Inventory (BPI)
timeFrame: Post-Operative Day 14
measure: Total Opioid Use Prior to Hospital Discharge
timeFrame: 24 hours
measure: Total Opioid Use End of Post-op Day 3
timeFrame: 72 hrs post-op
measure: Total Opioid Use at Post-op Day 14
timeFrame: Post-Operative Day 14
measure: Number of Participants With Adverse Events
timeFrame: Post-Operative Day 14
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Florida Hospital Orlando
state: Florida
Study officials:
affiliation: Florida Hospital Orlando
name: Georgine Lamvu, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Florida Hospital Orlando
name: Kenneth I Barron, MD
role: STUDY_DIRECTOR
References:
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. doi: 10.1016/s1074-3804(05)60578-6.
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. doi: 10.1016/s0029-7844(98)00303-2.
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;2014(3):CD007049. doi: 10.1002/14651858.CD007049.pub2.
citation: Bergese SD, Onel E, Portillo J. Evaluation of DepoFoam((R)) bupivacaine for the treatment of postsurgical pain. Pain Manag. 2011 Nov;1(6):539-47. doi: 10.2217/pmt.11.62.
citation: Golf M, Daniels SE, Onel E. A phase 3, randomized, placebo-controlled trial of DepoFoam(R) 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.
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.
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.
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. doi: 10.1097/00002508-200003000-00003.