Extended Release Local Anesthetic for Postsurgical Pain After Posterior Colporrhaphy and Perineorrhaphy

Extended Release Local Anesthetic for Postsurgical Pain After Posterior Colporrhaphy and Perineorrhaphy: A Randomized Controlled Study

The specific aim of this randomized double-blind clinical trial is to evaluate the effect of intraoperative infiltration of liposomal bupivacaine at the time of posterior colporrhaphy and/or perineorrhaphy on postsurgical pain scores during the first 72 hours after surgery as measured by visual analog scales (VAS) for patients undergoing surgery for pelvic organ prolapse. Study subjects are randomized to 30 mL of liposomal bupivacaine versus 30 mL of injectable normal saline administered in a standardized technique into the posterior vaginal compartment at the time of posterior repair and/or perineorrhaphy.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: Liposomal bupivacaine; Drug: Placebo - injection

Detailed Description

Liposomal bupivacaine (EXPAREL; Pacira Pharmaceuticals, San Diego, CA) is an extended release local anesthetic approved by the Food and Drug Administration since 2011 for the treatment of postsurgical pain. It is a multivesicular liposomal delivery system, consisting of a liquid bupivacaine core encapsulated by a phospholipid shell. This delivery technology allows for the slow, sustained release of bupivacaine over at least 72 hours.

Liposomal bupivacaine has been studied extensively in the general surgery and orthopedic surgery literature. Specifically, infiltration of liposomal bupivacaine after excisional hemorrhoidectomy has been shown to significantly lower postsurgical pain scores, decrease total postoperative opioid requirements, increase the number of patients who do not require any opioids after surgery, meaningfully delay the median time to first opioid use, and improve patient satisfaction with overall perioperative analgesia.

Posterior colporrhaphy and perineorrhaphy are pelvic reconstructive surgical procedures that are associated with significant postsurgical localized pain resulting from surgical incisions. Investigators hypothesize this localized postsurgical pain will benefit from treatment with an extended release local anesthetic formulation similar to hemorrhoidectomy. Intraoperative infiltration of a standard local anesthetic during posterior repair and perineorrhaphy has been shown to improve early analgesia and facilitate early postoperative recovery. These findings reiterate the need for studies investigating a slow-release, longer-acting local anesthetic formulation for patients undergoing posterior repair and/or perineorrhaphy - one that ideally can be integrated into an evidence-based, opioid-sparing postsurgical pain management regimen to improve perioperative care for the steadily growing pelvic reconstructive surgical patient population.

The primary study objective is to evaluate the effect of intraoperative infiltration of liposomal bupivacaine at the time of posterior colporrhaphy and/or perineorrhaphy on postsurgical pain scores during the first 72 hours after surgery as measured by visual analog scales (VAS).

Secondary objectives include to evaluate total opioid consumption during the first 72 postoperative hours, to evaluate patient satisfaction with postoperative analgesia, to evaluate time to first opioid administration postoperatively, to evaluate hospital length of stay, to evaluate length of stay in post-anesthesia care unit (PACU), to evaluate total hospital costs, to evaluate time to first bowel movement postoperatively, to evaluate rate of postoperative nausea and vomiting, to evaluate time to successful voiding trial, and to evaluate proportion of patients discharged home with a Foley catheter.

Patients will be approached for participation preoperatively and randomized in the operating room to either liposomal bupivacaine or injectable normal saline administered into the posterior vaginal compartment in a standardized technique. All concurrent minimally invasive pelvic reconstructive surgical procedures are allowed. Randomization will be stratified for abdominal versus purely vaginal surgery. Perioperative care is standardized. Data will be abstracted from the medical record. Additionally, subjects will be discharged home with a medication diary and pain scales. Subjects will record their pain every morning and every evening for the first 72 hours after surgery. Subjects will complete a satisfaction survey at their 2 week postoperative visit. Adverse postoperative outcomes will be collected for 30 days after surgery.

The study is powered to detect a 20 mm difference in a 100 mm visual analog scale for pain.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Women's Center for Pelvic Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• English-speaking women ages 18 and older undergoing posterior repair and/or perineorrhaphy at our institution for pelvic organ prolapse

Exclusion Criteria:

• Planned regional anesthesia
• Allergy or contraindication to bupivacaine
• Allergy or contraindication to opioids
• Allergy or contraindication to non-steroidal medications
• Planned laparotomy
• Chronic pain diagnosis and/or chronic narcotic use

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention; Receives 20 mL liposomal bupivacaine expanded with 10 mL of injectable sterile normal saline solution (0.9%) for a total of 30 mL injected in the posterior vaginal compartment in a standardized technique	Drug: Liposomal bupivacaine; Extended-release local anesthetic; Other Names: EXPAREL 266 mg
Placebo Comparator: Placebo; Receives 30 mL of injectable sterile normal 0.9% saline solution injected in the posterior vaginal compartment in a standardized technique	Drug: Placebo - injection; Injectable normal saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Pain	As measured by a 100 mm Visual Analog Scale (VAS). This scale ranges from 0-100 mm with 0 mm indicating no pain and 100 mm indicating the most pain. The study is powered to detect a decrease in postoperative pain by 20 mm on this scale, which is considered to be a clinically meaningful difference in prior studies. Results will be reported as mean pain scores at each time point (night of surgery, morning and evening for the first 72 hours after surgery, i.e. until postoperative day#3).	Night of surgery (POD#0), POD#1 morning, POD#1 evening, POD#2 morning, POD#2 evening, POD#3 morning, POD#3 evening

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reporting Satisfaction With Pain Control	As measured by a 5-question satisfaction survey administered at a 2 week postoperative visit. The survey includes Likert scale responses ranging from very unsatisfied to very satisfied with the surgical experience and specifically analgesia. "Patient Satisfaction" was defined as response "satisfied" or "very satisfied" on the Likert Scale. Average responses will be reported.	2 weeks after surgery
Time to First Opioid Administration	Median time until first opioid administered after surgery	Assessed up to 72 hours after surgery
Total Opioid Administration	Measured in milligram morphine equivalents	Cumulatively, over a time period of 72 hours after surgery
Number of Antiemetic Doses Required Per Participant While Inpatient	Number of as-needed antiemetic doses patient received while in the hospital after surgery	Cumulatively, over a time period of 72 hours after surgery
Hospital Length of Stay	Total length of hospital stay measured in hours, including readmissions	Assessed until 30 days after surgery
Length of Stay in Post-anesthesia Care Unit (PACU)	Total length of stay in PACU measured in minutes	Assessed up to 72 hours after surgery
Number of Participants Who Had a Bowel Movement Within the First 3 Postoperative Days	As recorded by patient - patients were asked each postoperative day (i.e. POD#0, POD#1, POD#2, POD#3) if they had a bowel movement that day, yes or no.	72 hours after surgery
Voiding Trial Failures	Proportion of patients discharged home with Foley catheters after failed voiding trials in the hospital	2 weeks after surgery
Number of Patients With Adverse Events	Total adverse postoperative events	Assessed until 30 days after surgery

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Investigators: Principal Investigator: Sarah Evans, MD, Women's Center for Pelvic Health

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2018
• Primary Completion (Actual): March 12, 2019
• Study Completion (Actual): March 31, 2019

Study Registration Dates

• First Submitted: March 13, 2019
• First Submitted That Met QC Criteria: March 14, 2019
• First Posted (Actual): March 15, 2019

Study Record Updates

• Last Update Posted (Actual): September 13, 2022
• Last Update Submitted That Met QC Criteria: August 24, 2022
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: liposomal bupivacaine; posterior repair
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: Pro00024327

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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