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

Phase 4

Completed

• Conditions: Postoperative Pain
• Interventions: Drug: Placebo - injection; Drug: Liposomal bupivacaine

• Registration Number: NCT03875664
• Lead Sponsor: Wake Forest University Health Sciences

Brief Summary

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.

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 Timeline

• Study Start: 2018-07-23
• Primary Completion: 2019-03-12
• Study First Submitted: 2019-03-13
• Study First Submitted QC: 2019-03-14
• Study First Posted: 2019-03-15
• Study Completion: 2019-03-31
• Results First Submitted: 2020-04-17
• Status Verified: 2020-05
• Results First Submitted QC: 2020-05-01
• Results First Posted: 2020-05-13
• Last Update Submitted: 2022-08-24
• Last Update Posted: 2022-09-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 72

Inclusion Criteria

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo - injection	Receives 30 mL of injectable sterile normal 0.9% saline solution injected in the posterior vaginal compartment in a standardized technique
Intervention	Liposomal bupivacaine	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

Primary Outcome Measures

Name	Time	Method
Postoperative Pain	Night of surgery (POD#0), POD#1 morning, POD#1 evening, POD#2 morning, POD#2 evening, POD#3 morning, POD#3 evening	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).

Secondary Outcome Measures

Name	Time	Method
Number of Participants Who Had a Bowel Movement Within the First 3 Postoperative Days	72 hours after surgery	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.
Number of Patients With Adverse Events	Assessed until 30 days after surgery	Total adverse postoperative events
Total Opioid Administration	Cumulatively, over a time period of 72 hours after surgery	Measured in milligram morphine equivalents
Voiding Trial Failures	2 weeks after surgery	Proportion of patients discharged home with Foley catheters after failed voiding trials in the hospital
Time to First Opioid Administration	Assessed up to 72 hours after surgery	Median time until first opioid administered after surgery
Number of Antiemetic Doses Required Per Participant While Inpatient	Cumulatively, over a time period of 72 hours after surgery	Number of as-needed antiemetic doses patient received while in the hospital after surgery
Number of Participants Reporting Satisfaction With Pain Control	2 weeks after surgery	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.
Hospital Length of Stay	Assessed until 30 days after surgery	Total length of hospital stay measured in hours, including readmissions
Length of Stay in Post-anesthesia Care Unit (PACU)	Assessed up to 72 hours after surgery	Total length of stay in PACU measured in minutes

Trial Locations

Locations (1)

Women's Center for Pelvic Health; 🇺🇸 Charlotte, North Carolina, United States