Liposomal Bupivacaine in Vaginal Hysterectomy

• Sponsor: Mayo Clinic (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03907033
• Collaborator: Pacira Pharmaceuticals, Inc (Industry)
• Enrollment: 28
• Location: 1
• Arms: 2
• Actual Duration (Months): 22.6
• Patients Per Site Per Month: 1.2

Study Details

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
• 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.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: Sep 3, 2019
• Actual Primary Completion Date: Jul 23, 2021
• Actual Study Completion Date: Jul 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 Names: 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 [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 [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 [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 [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 [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 [24, 48, and 72 hours post-surgery]

   Number of times the patient vomited

5. Urinary Retention [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 [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

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	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)

• Study Protocol and Statistical Analysis Plan - Sep 27, 2019

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

• 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.
• 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.
• 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.
• 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.
• 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.

• Responsible Party: Johnny Yi, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT03907033
• Other Study ID Numbers: 15-008413
• First Posted: Apr 8, 2019
• Last Update Posted: Oct 15, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• 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

Study Results

Participant Flow

Arm/Group Title	Standard Bupivacaine	Liposomal Bupivacaine
Arm/Group Description	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. 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.	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 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. 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.
Period Title: Overall Study
STARTED	14	14
COMPLETED	14	14
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Standard Bupivacaine	Liposomal Bupivacaine	Total
Arm/Group Description	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. 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.	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 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. 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.	Total of all reporting groups
Overall Participants	14	14	28
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.2 (10.96)	60.4 (12.56)	57.8 (11.86)
Sex: Female, Male (Count of Participants)
Female	14 100%	14 100%	28 100%
Male	0 0%	0 0%	0 0%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	14 100%	14 100%	28 100%

Outcome Measures

1. Primary Outcome

Title	Total Post-surgical Opioid Medication Use
Description	Participants post-surgical analgesic medication use of IV hydrocodone and oxycodone measured in morphine equivalents (ME)
Time Frame	First 72 hours following surgery completion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Bupivacaine	Liposomal Bupivacaine
Arm/Group Description	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. 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.	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 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. 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.
Measure Participants	14	14
Hydrocodone	0	0
Oxycodone	30.0	30.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Bupivacaine, Liposomal Bupivacaine
	Comments	Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm for Hydrocodone use
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Standard Bupivacaine, Liposomal Bupivacaine
	Comments	Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm for Oxycodone use
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Primary Outcome

Title	Total Post-surgical Analgesic Medication Use
Description	Participants post-surgical analgesic medication use of Ibuprofen and acetaminophen measured in milligrams (mg)
Time Frame	First 72 hours following surgery completion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Bupivacaine	Liposomal Bupivacaine
Arm/Group Description	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. 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.	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 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. 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.
Measure Participants	14	14
Ibuprofen	5400.0	4800.0
Tylenol	6500.0	6500.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Bupivacaine, Liposomal Bupivacaine
	Comments	Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm for Ibuprofen use
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.248
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Standard Bupivacaine, Liposomal Bupivacaine
	Comments	Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm for Tylenol use
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Mean PACU Visual Analog Scale (VAS) (0-10) Pain Score
Description	Scale Ranges from 0 (no pain) to 10 (extreme pain)
Time Frame	Assessed while patient in PACU for recovery post-surgery per standard procedure

Outcome Measure Data

Analysis Population Description

Data not collected or analyzed

Arm/Group Title	Standard Bupivacaine	Liposomal Bupivacaine
Arm/Group Description	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. 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.	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 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. 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.
Measure Participants	0	0

4. Secondary Outcome

Title	VAS Pain Score at 24, 48, and 72 Hours Post-surgery Completion
Description	Scale Ranges from 0 (no pain) to 10 (extreme pain)
Time Frame	24, 48, and 72 hours post-surgery completion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Bupivacaine	Liposomal Bupivacaine
Arm/Group Description	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. 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.	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 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. 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.
Measure Participants	14	14
24 hours post-surgery	3.1	3.5
48 hours post-surgery	2.5	3.6
72 hours post-surgery	1.6	2.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Bupivacaine, Liposomal Bupivacaine
	Comments	Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm 24 hours post-surgery
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.846
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Standard Bupivacaine, Liposomal Bupivacaine
	Comments	Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm 48 hours post-surgery
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.490
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Standard Bupivacaine, Liposomal Bupivacaine
	Comments	Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm 72 hours post-surgery
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.564
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Nausea at 24, 48, and 72 Hours Post-surgery Completion
Description	Number of times patient reported feeling nauseous
Time Frame	24, 48, and 72 hours post-surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Bupivacaine	Liposomal Bupivacaine
Arm/Group Description	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. 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.	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 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. 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.
Measure Participants	14	14
24 hours post-surgery	0.0	0.0
48 hours post-surgery	0.0	0.0
72 hours post-surgery	0.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Bupivacaine, Liposomal Bupivacaine
	Comments	Standard Bupivacaine study arm compared to Liposomal Bupivacaine arm at 24 hours post-surgery
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.264
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Standard Bupivacaine, Liposomal Bupivacaine
	Comments	Standard Bupivacaine study arm compared to Liposomal Bupivacaine arm at 48 hours post-surgery
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.970
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Standard Bupivacaine, Liposomal Bupivacaine
	Comments	Standard Bupivacaine study arm compared to Liposomal Bupivacaine arm at 72 hours post-surgery
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.536
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Secondary Outcome

Title	Emesis at 24, 48, and 72 Hours Post-surgery Completion
Description	Number of times the patient vomited
Time Frame	24, 48, and 72 hours post-surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Bupivacaine	Liposomal Bupivacaine
Arm/Group Description	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. 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.	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 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. 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.
Measure Participants	14	14
24 hours post-surgery	0.0	0.0
48 hours post-surgery	0.0	0.0
72 hours post-surgery	0.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Bupivacaine, Liposomal Bupivacaine
	Comments	Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm at 24 hours post-surgery
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.957
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Standard Bupivacaine, Liposomal Bupivacaine
	Comments	Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm at 48 hours post-surgery
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.353
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Standard Bupivacaine, Liposomal Bupivacaine
	Comments	Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm at 72 hours post-surgery
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.165
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Secondary Outcome

Title	Urinary Retention
Description	Number of patients who had post-void residual (PVR) >150cc's at voiding trial prior to discharge
Time Frame	At voiding trial prior to discharge from hospital, approximately 72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Bupivacaine	Liposomal Bupivacaine
Arm/Group Description	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. 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.	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 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. 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.
Measure Participants	14	14
Count of Participants [Participants]	1 7.1%	1 7.1%

8. Secondary Outcome

Title	Patient Satisfaction With Pain Management at 72 Hours and 7-10 Days Post Surgery
Description	Assessed on 0-10 scale (0 being worst level of satisfaction, 10 being best level)
Time Frame	72 hours and 7-10 days post surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Standard Bupivacaine	Liposomal Bupivacaine
Arm/Group Description	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. 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.	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 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. 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.
Measure Participants	14	14
72 hours post-surgery	10.0	9.5
7-10 days post-surgery	10.00	9.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Bupivacaine, Liposomal Bupivacaine
	Comments	Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm at 72 hours post-surgery
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.802
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Standard Bupivacaine, Liposomal Bupivacaine
	Comments	Standard Bupivacaine study arm compared to Liposomal Bupivacaine study arm at 7-10 days post-surgery
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.656
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	Adverse events were collected post operative on all participants, approximately 7 days.
Arm/Group Title	Standard Bupivacaine		Liposomal Bupivacaine
Arm/Group Description	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. 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.		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 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. 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.
All Cause Mortality
	Standard Bupivacaine		Liposomal Bupivacaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)
Serious Adverse Events
	Standard Bupivacaine		Liposomal Bupivacaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Standard Bupivacaine		Liposomal Bupivacaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/14 (21.4%)		2/14 (14.3%)
Renal and urinary disorders
Urinary Retention	1/14 (7.1%)		1/14 (7.1%)
Urinary Incontinence	1/14 (7.1%)		1/14 (7.1%)
Surgical and medical procedures
Protruding sutures	1/14 (7.1%)		0/14 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.