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

Surgery Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04117074
• Other study ID #: J17157
• Secondary ID: IRB00223229
• Status: Recruiting
• Phase: Phase 3
• Start date: April 14, 2021
• Est. completion date: September 2025

Study information

• Verified date: June 2023
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: Rebecca L Stone, MD
• Phone: 410-955-8240
• Email: rstone15[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: September 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Analgesia
• Surgery

Intervention

Drug:
• Liposomal bupivacaine
Surgical site infiltration with 20 mL liposomal bupivacaine prior to laparotomy closure.

Other:
• Thoracic epidural analgesia (bupivacaine)
Perioperative bupivacaine based thoracic epidural placed preoperatively.

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Pacira Pharmaceuticals, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Analgesia as assessed by pain intensity scores on a visual analog scale	Pain intensity will be measured using visual analog scale (VAS) pain intensity scores. The VAS scores pain intensity on a scale of 0-10, where 0 is no pain and 10 is the most severe pain.	0 to 48 hours postoperatively
Primary	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	Change in 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 will be compared between the two arms. The QoR-15 is a validated instrument designed to measure the major domains of postoperative recovery including functional independence, physical comfort/pain, psychological/emotional well-being, cognition and satisfaction with a score of 0 indicating the poorest patient-perceived quality of recovery and 150 indicating the highest patient-perceived quality of recovery.	Days 1 through 7 post-intervention
Secondary	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
Secondary	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
Secondary	Mobility as assessed by the Johns Hopkins Highest Level of Mobility (JH-HLM) scale	The Johns Hopkins Highest Level of Mobility scale is an ordinal scale from 1 to 8, with numbers representing mobility milestones that patients accomplish, based on observation. Patients who score a 2 have some type of bed mobility, while those scoring an 8 can walk more than 250 feet.	Up to 7 days post-intervention
Secondary	Degree of sedation 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
Secondary	Length of stay	The duration of the index inpatient postoperative admission in days.	Up to 1 year
Secondary	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
Secondary	Total intravenous fluids administered in mL		Arrival in recovery through hospital discharge, up to 1 year
Secondary	Amount of Vasopressor required	Total amount (micrograms) of vasopressor required.	Start of operation through hospital discharge, up to 1 year
Secondary	Duration of Vasopressor administration	Duration (minutes) of vasopressor administration.	Start of operation through hospital discharge, up to 1 year
Secondary	Number of postoperative complications	Number of postoperative complications (Maryland Hospital Acquired Conditions).	Day of admission through postoperative day 30
Secondary	Total direct cost of TEA placement and LB surgical site infiltration	Pharmacy and equipment costs, professional fees and the dollar-value of total OR time required for administration of each intervention will be compared.	Up to 1 year
Secondary	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
Secondary	Change in Serum adrenocorticotropic hormone (ACTH)	Serum ACTH level in pg/mL.	Baseline and postoperative day 7
Secondary	Change in Epinephrine level (pg/mL)		Baseline and postoperative day 7
Secondary	Change in Total cortisol level (microgram/dL)		Baseline and postoperative day 7
Secondary	Change in Anti-diuretic hormone (ADH) level	ADH level in pg/mL.	Baseline and postoperative day 7
Secondary	Change in Interleukin-6 level (pg/mL)		Baseline and postoperative day 7
Secondary	Change in Atrial natriuretic peptide (ANP) level	ANP level in pg/mL.	Baseline and postoperative day 7
Secondary	Change in Syndecan-1 level (pg/mL)		Baseline and postoperative day 7
Secondary	Change in Glycosaminoglycans level (ng/mL)		Baseline and postoperative day 7
Secondary	Change in Endothelial glycocalyx constituents (ng/mL)		Baseline and postoperative day 7
Secondary	Change in C-reactive protein level (ng/mL)		Baseline and postoperative day 7
Secondary	Change in Tumor necrosis factor alpha (TNF-a) level	TNF-a level in pg/mL.	Baseline and postoperative day 7
Secondary	Change in Salivary cortisol (microgram/dL) level		Baseline and postoperative day 7
Secondary	Rate of 30-day hospital readmission	Rate of 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