Liposomal Bupivacaine in Vaginal Hysterectomy

• ClinicalTrials.gov Identifier: NCT03907033
• Recruitment Status: Terminated
• First Posted: April 8, 2019
• Results First Posted: October 15, 2021
• Last Update Posted: October 15, 2021
• Sponsor: Mayo Clinic
• Collaborator: Pacira Pharmaceuticals, Inc
• Information provided by (Responsible Party): Johnny Yi, Mayo Clinic

Study Description

Brief Summary:

The aim of this study is to compare the effects of preemptive analgesia using liposomal bupivacaine mixed with bupivacaine HCl, versus bupivacaine HCl alone for uterosacral ligament injection in patients undergoing vaginal hysterectomy. We hypothesize that the group receiving a combination of liposomal bupivacaine and bupivacaine HCl will report superior postoperative pain management. Enhancement in pain control should confer a decrease in opioid and other analgesic medication requirements, which may contribute to decreased nausea, vomiting, and higher overall patient satisfaction with pain control.

Condition or disease	Intervention/treatment	Phase
Vaginal Hysterectomy	Drug: Liposomal bupivacaine; Drug: Bupivacaine Hydrochloride	Phase 4

Detailed Description:

Prior to surgery, patients are assigned by chance (like a coin toss) to receive either the bupivacaine HCl injection at the time of surgery or bupivacaine HCl plus liposomal bupivacaine. Patients and the Principal Investigator cannot choose the study group. Patients will have a 50% chance of being assigned to either group; however, regardless of which group they are assigned to, the medical record will show that they received liposomal bupivacaine. The injections will be given in the vaginal area when the patient is under anesthesia.

After surgery, patients will be asked to record their pain, medication use, pain scores and symptoms in a diary for each 12 hour interval up to 72 hours. Someone will also call twice a day during the 72 hours after surgery to ask about pain level and pain medication use.

Patients will also receive a phone call 7-10 days after the surgery to ask about their recovery and pain level.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Patients will be randomized to receive either the bupivacaine HCl injection at the time of surgery or bupivacaine HCl plus liposomal bupivacaine.
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: This will be a blinded study where investigators, patients, and care providers will be blinded to treatment assignment.
• Primary Purpose: Prevention
• Official Title: Preemptive Local Analgesia With Liposomal Bupivacaine in Vaginal Hysterectomy: A Randomized Controlled Study
• Actual Study Start Date: September 3, 2019
• Actual Primary Completion Date: July 23, 2021
• Actual Study Completion Date: July 23, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Standard Bupivacaine; Patients in the control group will receive 0.25% bupivacaine hydrochloride (bupivacaine HCl). 10cc will be injected bilaterally into each uterosacral ligament prior to the colpotomy incision. After entry into the posterior cul-de-sac, an additional 10cc of will be injected bilaterally into the deeper uterosacral ligaments.	Drug: Bupivacaine Hydrochloride; We currently administer local plain bupivacaine during vaginal hysterectomy to decrease pain in the postoperative period. Bupivacaine is an anesthetic that works by blocking nerve conduction and producing a numbing effect.
Experimental: Liposomal Bupivacaine; Patients in the study group will receive a mixture of 0.5% bupivacaine HCl and liposomal bupivacaine in 1:1 ratio. 10cc of the mixture will be injected bilaterally into each uterosacral ligament prior to the colpotomy incision. After entry into the posterior cul-de-sac, an additional 10cc will be injected bilaterally into the deeper uterosacral ligaments	Drug: Liposomal bupivacaine; Liposomal bupivacaine is a novel formulation of local bupivacaine and allows prolonged release of the medication, thereby providing longer lasting effects. It is approved by the FDA and has been shown to provide excellent pain control after surgery.; Other Name: Exparel; Drug: Bupivacaine Hydrochloride; We currently administer local plain bupivacaine during vaginal hysterectomy to decrease pain in the postoperative period. Bupivacaine is an anesthetic that works by blocking nerve conduction and producing a numbing effect.

Outcome Measures

Primary Outcome Measures :

1. Total Post-surgical Opioid Medication Use [ Time Frame: First 72 hours following surgery completion ]
   Participants post-surgical analgesic medication use of IV hydrocodone and oxycodone measured in morphine equivalents (ME)
2. Total Post-surgical Analgesic Medication Use [ Time Frame: First 72 hours following surgery completion ]
   Participants post-surgical analgesic medication use of Ibuprofen and acetaminophen measured in milligrams (mg)

Secondary Outcome Measures :

1. Mean PACU Visual Analog Scale (VAS) (0-10) Pain Score [ Time Frame: Assessed while patient in PACU for recovery post-surgery per standard procedure ]
   Scale Ranges from 0 (no pain) to 10 (extreme pain)
2. VAS Pain Score at 24, 48, and 72 Hours Post-surgery Completion [ Time Frame: 24, 48, and 72 hours post-surgery completion ]
   Scale Ranges from 0 (no pain) to 10 (extreme pain)
3. Nausea at 24, 48, and 72 Hours Post-surgery Completion [ Time Frame: 24, 48, and 72 hours post-surgery ]
   Number of times patient reported feeling nauseous
4. Emesis at 24, 48, and 72 Hours Post-surgery Completion [ Time Frame: 24, 48, and 72 hours post-surgery ]
   Number of times the patient vomited
5. Urinary Retention [ Time Frame: At voiding trial prior to discharge from hospital, approximately 72 hours ]
   Number of patients who had post-void residual (PVR) >150cc's at voiding trial prior to discharge
6. Patient Satisfaction With Pain Management at 72 Hours and 7-10 Days Post Surgery [ Time Frame: 72 hours and 7-10 days post surgery ]
   Assessed on 0-10 scale (0 being worst level of satisfaction, 10 being best level)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

INCLUSION CRITERIA

1. Women 18-85 who will be having an outpatient vaginal hysterectomy with or without concurrent prolapse repair surgery at Mayo Clinic Hospital in Arizona

EXCLUSION CRITERIA

1. Known history of hepatic (liver) disease as evidenced by an AST or ALT that is greater than normal values
2. Known history of renal (kidney) disease as evidenced by a serum creatinine that is greater than normal values
3. Known history of prolonged QT (QTc greater than 500 m/s)
4. Opiate tolerance as noted by daily use of greater than 20 mg morphine daily oral equivalents per day for a minimum of 1 month prior to surgery
5. Allergy or contraindication to amide local anesthetics, celecoxib, ketorolac, NSAIDs, acetaminophen, gabapentin, sulfa drugs, or ondansetron
6. Allergy to both oxycodone and hydromorphone
7. Patients with acute gastrointestinal bleed that has occurred less than 6 months prior to study enrollment
8. Adults lacking the ability to consent

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic in Arizona

Phoenix, Arizona, United States, 85054

Sponsors and Collaborators

Mayo Clinic

Pacira Pharmaceuticals, Inc

Investigators

• Principal Investigator: Jeffrey L Cornella; Mayo Clinic

  Study Documents (Full-Text)

Documents provided by Johnny Yi, Mayo Clinic:

Study Protocol and Statistical Analysis Plan  [PDF] September 27, 2019

More Information

Additional Information:

Mayo Clinic Clinical Trials 

Publications:

Long JB, Eiland RJ, Hentz JG, Mergens PA, Magtibay PM, Kho RM, Magrina JF, Cornella JL. Randomized trial of preemptive local analgesia in vaginal surgery. Int Urogynecol J Pelvic Floor Dysfunct. 2009 Jan;20(1):5-10. doi: 10.1007/s00192-008-0716-6. Epub 2008 Oct 2.

Ilfeld BM, Viscusi ER, Hadzic A, Minkowitz HS, Morren MD, Lookabaugh J, Joshi GP. Safety and Side Effect Profile of Liposome Bupivacaine (Exparel) in Peripheral Nerve Blocks. Reg Anesth Pain Med. 2015 Sep-Oct;40(5):572-82. doi: 10.1097/AAP.0000000000000283.

Bergese SD, Ramamoorthy S, Patou G, Bramlett K, Gorfine SR, Candiotti KA. Efficacy profile of liposome bupivacaine, a novel formulation of bupivacaine for postsurgical analgesia. J Pain Res. 2012;5:107-16. doi: 10.2147/JPR.S30861. Epub 2012 May 1.

Hutchins J, Delaney D, Vogel RI, Ghebre RG, Downs LS Jr, Carson L, Mullany S, Teoh D, Geller MA. Ultrasound guided subcostal transversus abdominis plane (TAP) infiltration with liposomal bupivacaine for patients undergoing robotic assisted hysterectomy: A prospective randomized controlled study. Gynecol Oncol. 2015 Sep;138(3):609-13. doi: 10.1016/j.ygyno.2015.06.008. Epub 2015 Jun 6.

Mont MA, Beaver WB, Dysart SH, Barrington JW, Del Gaizo DJ. Local Infiltration Analgesia With Liposomal Bupivacaine Improves Pain Scores and Reduces Opioid Use After Total Knee Arthroplasty: Results of a Randomized Controlled Trial. J Arthroplasty. 2018 Jan;33(1):90-96. doi: 10.1016/j.arth.2017.07.024. Epub 2017 Jul 25. Erratum in: J Arthroplasty. 2019 Feb;34(2):399-400.

Kalogera E, Bakkum-Gamez JN, Jankowski CJ, Trabuco E, Lovely JK, Dhanorker S, Grubbs PL, Weaver AL, Haas LR, Borah BJ, Bursiek AA, Walsh MT, Cliby WA, Dowdy SC. Enhanced recovery in gynecologic surgery. Obstet Gynecol. 2013 Aug;122(2 Pt 1):319-328. doi: 10.1097/AOG.0b013e31829aa780.

• Responsible Party: Johnny Yi, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT03907033
• Other Study ID Numbers: 15-008413
• First Posted: April 8, 2019
• Results First Posted: October 15, 2021
• Last Update Posted: October 15, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Bupivacaine; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents