Thoracic Epidural Analgesia vs Surgical Site Infiltration With Liposomal Bupivacaine Following Open Gynecologic Surgery

A Non-Inferiority Randomized Trial Comparing the Impact of Thoracic Epidural Analgesia Versus Surgical Site Infiltration With Liposomal Bupivicaine on the Postoperative Recovery of Patients Following Open Gynecologic Surgery

The goal of this study is to test the hypothesis that surgical site infiltration with liposomal bupivacaine (LB) is non-inferior to and more cost effective than thoracic epidural analgesia (TEA) for patients undergoing open gynecologic surgery on an established enhanced recovery program (ERP) using a non-inferiority randomized trial design. The impact of TEA and surgical site infiltration with LB on neuroendocrine and inflammatory mediators of surgical stress response (SSR) will also be investigated as a translational endpoint.

Study Overview

• Status: Completed
• Conditions: Analgesia; Surgery
• Intervention / Treatment: Other: Thoracic epidural analgesia (bupivacaine); Drug: Liposomal bupivacaine

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Individuals ≥ 18 years of age
• Planned laparotomy by the gynecologic oncology service at the sponsor institution.

Exclusion Criteria:

• Individuals who have a contraindication to thoracic epidural analgesia
• Individuals with a coagulation disorder
• Individuals with an infection at the site of epidural placement
• Individuals with intracranial pathology such as non-communicating increased intracranial pressure or obstruction of cerebrospinal fluid flow related to mass lesions
• Individuals with spinal pathology: abnormal spine anatomy, surgical fusion, or spinal column lesions
• Individuals who have a contraindication to liposomal bupivacaine
• Individuals with a known allergic reaction to liposomal bupivacaine
• Individuals with Childs-Pugh Class B or C liver disease
• Individuals who have a history of long-term opioid use for chronic pain, defined as use of opioid pain medications for ≥4 weeks prior to surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Thoracic Epidural Analgesia with bupivicaine; Thoracic epidural analgesia (TEA): 0.125 % Bupivicaine infusion (5-7 milliliter [mL] per hour) intraoperatively with a 3 mL bolus at the end of the operative procedure just prior to emergence from general anesthesia. Postoperatively 0.0625% Bupivicaine until patient-controlled epidural analgesia (PCEA) pump. PCEA pump 0.0625% bupivacaine at 5-7 mL per hour infusion with a 3 mL q20 minutes demand. PCEA discontinuation with oral tolerance.	Other: Thoracic epidural analgesia (bupivacaine); Perioperative bupivacaine based thoracic epidural placed preoperatively.
Experimental: Arm 2: Surgical Site Infiltration with Liposomal Bupivacaine; Liposomal bupivacaine (LB) surgical site infiltration: A single 20 mL liposomal bupivacaine vial containing 266 mg of free-base bupivacaine will be mixed with 60 mL of 0.25% bupivacaine hydrochloride (HCl) and then diluted in preservative-free sterile 0.9% saline for maximal volume not to exceed 300 mL. Dilution with 0.9% saline will be dependent upon length of surgical incision per protocol. The solution will be injected using 22-gauge needle in equal distribution into the peritoneum, along the fascia and into the subcutaneous tissues of the surgical wound by trained faculty surgeons.	Drug: Liposomal bupivacaine; Surgical site infiltration with 20 mL liposomal bupivacaine prior to laparotomy closure.; Other Names: Exparel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analgesia Assessed by the Area Under the Curve of Visual Analog Scale Pain Intensity Scores	Pain intensity was measured using the Visual Analog Scale (VAS), a 0-10 scale where 0 indicates no pain and 10 indicates worst pain imaginable. VAS scores were assessed hourly from 0 to 48 hours postoperatively. The area under the curve (AUC) was calculated as the sum of hourly VAS scores over 48 hours, yielding a possible range of 0 to 480. Higher scores indicate greater cumulative pain burden and worse outcomes.	0 to 48 hours postoperatively
Total Opioid Consumption	Total opioid consumption in IV mg morphine equivalents from 0 to 48 hours postoperatively will be compared between the two arms.	0 to 48 hours postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-perceived Quality of Recovery as Assessed by the Quality of Recovery-15 Instrument (QoR-15)	Mean patient-perceived quality of recovery scores using the Quality of Recovery-15 instrument (QoR-15) on postoperative days 1 to 7 were compared between the two arms. The QoR-15 is a validated instrument designed to measure the major domains of postoperative recovery with a score range of 0 indicating the poorest patient-perceived quality of recovery to 150 indicating the highest patient-perceived quality of recovery. QoR-15 scores were analyzed using a linear mixed-effects model for repeated measures across postoperative days 1-7. The single value reported for each arm represents the model-based estimated marginal mean (least squares mean) across all assessed postoperative days using all available observed data without imputation. This reflects an overall POD1-7 summary rather than a score from a single postoperative day.	Days 1 through 7 post-intervention
Time (Days) to Return of Bowel Function (ROBF)	Time to ROBF is defined as the time lapse from the day of surgery (DOS) to the day oral intake is consistently tolerated for 48 hours without vomiting.	Up to 7 days post-intervention
Number of Participants With Postoperative Ileus	Ileus is defined as the occurrence of postoperative nausea and vomiting requiring cessation of oral intake and initiation of intravenous hydration +/- nasogastric tube placement following documented ROBF or the persistence of these symptoms beyond postoperative day 5 in the absence of ROBF.	Up to 7 days post-intervention
Mobility as Assessed by the Johns Hopkins Highest Level of Mobility (JH-HLM) Scale	The Johns Hopkins Highest Level of Mobility (JH-HLM) scale is an ordinal scale ranging from 1 to 8, with higher scores indicating better mobility. Scores represent observed mobility milestones achieved by the patient; a score of 1 indicates lying in bed, while a score of 8 indicates walking 250 feet or more. Mobility was analyzed using a linear mixed-effects model for repeated measures across postoperative days 1-7. The single value reported for each arm represents the model-based estimated marginal mean (least squares mean) across all assessed postoperative days using all available observed data without imputation. This reflects an overall POD1-7 summary rather than a single postoperative day.	Up to 7 days post-intervention
Number of Participants With Sedation Score ≥2 as Assessed by the Pasero Opioid-Induced Sedation Scale	The Pasero Opioid-induced Sedation Scale (POSS) is a valid, reliable tool used to assess sedation when administering opioid medications to manage pain. It uses an ordinal scale of 1-4 with a POSS of 1 or 2 indicating an acceptable level of sedation and a score of 3 or 4 indicating over-sedation and the need for intervention, such as the administration of a reversal agent in the case of a score of 4.	Up to 7 days post-intervention
Length of Stay	The duration of the index inpatient postoperative admission in days.	Up to 1 year
Time to Postoperative Diuresis	Time to diuresis is defined as the recovery time in hours to achieve a net negative fluid balance sustained over a 24 hour time period.	Arrival in recovery through hospital discharge, up to 1 year
Total Intravenous Fluids Administered in mL	Total intravenous fluids administered in mL.	Arrival in recovery through hospital discharge, up to 1 year
Amount of Vasopressor Required	Total amount (micrograms) of Levophed required.	Start of operation through hospital discharge, up to 1 year
Duration of Vasopressor Administration	Duration (minutes) of vasopressor administration.	Start of operation through hospital discharge, up to 1 year
Number Participants With Postoperative Complications	Number of participants with postoperative complications (Maryland Hospital Acquired Conditions).	Day of admission through postoperative day 30
Total Direct Cost of TEA Placement and LB Surgical Site Infiltration	Total Direct Cost (Pharmacy and equipment costs, professional fees and the dollar-value of total OR time required for administration of each intervention)	Up to 1 year
Post-discharge Narcotic Utilization	Patient reported total outpatient narcotic use in IV morphine (mg) equivalents on nurse phone survey administered on postoperative day 14.	Postoperative day 14
Number of Participants With 30-day Hospital Readmission	Number of participants with 30-day hospital readmission assessed as the number of participants who get readmitted within 30 days of discharge from the initial admission.	Up to 30 days post discharge from index admission

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Serum Adrenocorticotropic Hormone (ACTH)	Serum ACTH level in pg/mL.	Baseline and postoperative day 7
Change in Epinephrine Level (pg/mL)		Baseline and postoperative day 7
Change in Total Cortisol Level (Microgram/dL)		Baseline and postoperative day 7
Change in Anti-diuretic Hormone (ADH) Level	ADH level in pg/mL.	Baseline and postoperative day 7
Change in Interleukin-6 Level (pg/mL)		Baseline and postoperative day 7
Change in Syndecan-1 Level (pg/mL)		Baseline and postoperative day 7
Change in Atrial Natriuretic Peptide (ANP) Level	ANP level in pg/mL.	Baseline and postoperative day 7
Change in Glycosaminoglycans Level (ng/mL)		Baseline and postoperative day 7
Change in Endothelial Glycocalyx Constituents (ng/mL)		Baseline and postoperative day 7
Change in C-reactive Protein Level (ng/mL)		Baseline and postoperative day 7
Change in Tumor Necrosis Factor Alpha (TNF-α) Level	TNF-α level in pg/mL.	Baseline and postoperative day 7
Change in Salivary Cortisol (Microgram/dL) Level		Baseline and postoperative day 7

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Pacira Pharmaceuticals, Inc
• Investigators: Principal Investigator: Rebecca L Stone, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2021
• Primary Completion (Actual): March 3, 2025
• Study Completion (Actual): March 17, 2025

Study Registration Dates

• First Submitted: October 3, 2019
• First Submitted That Met QC Criteria: October 3, 2019
• First Posted (Actual): October 7, 2019

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Agnosia; Organic Chemicals; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Anilides; Amides; Aniline Compounds; Amines; Beverages; Plant Preparations; Biological Products; Complex Mixtures; Bupivacaine; Tea
• Other Study ID Numbers: J17157; IRB00223229 (Other Identifier: JHM IRB)

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.: Yes