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

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Primary Purpose

Status

Recruiting

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Liposomal bupivacaine

Thoracic epidural analgesia (bupivacaine)

About this trial

This is an interventional treatment trial for Surgery

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleAccepts Healthy Volunteers

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.

Sites / Locations

Johns Hopkins HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm 1: Thoracic Epidural Analgesia with bupivicaine

Arm 2: Surgical Site Infiltration with Liposomal Bupivacaine

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Total opioid consumption

Total opioid consumption in IV mg morphine equivalents from 0 to 48 hours postoperatively will be compared between the two arms.

Secondary Outcome Measures

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.

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.

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.

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.

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.

Length of stay

The duration of the index inpatient postoperative admission in days.

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.

Total intravenous fluids administered in mL

Amount of Vasopressor required

Total amount (micrograms) of vasopressor required.

Duration of Vasopressor administration

Duration (minutes) of vasopressor administration.

Number of postoperative complications

Number of postoperative complications (Maryland Hospital Acquired Conditions).

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.

Post-discharge narcotic utilization

Patient reported total outpatient narcotic use in IV morphine (mg) equivalents on nurse phone survey administered on postoperative day 14.

Change in Serum adrenocorticotropic hormone (ACTH)

Serum ACTH level in pg/mL.

Change in Epinephrine level (pg/mL)

Change in Total cortisol level (microgram/dL)

Change in Anti-diuretic hormone (ADH) level

ADH level in pg/mL.

Change in Interleukin-6 level (pg/mL)

Change in Atrial natriuretic peptide (ANP) level

ANP level in pg/mL.

Change in Syndecan-1 level (pg/mL)

Change in Glycosaminoglycans level (ng/mL)

Change in Endothelial glycocalyx constituents (ng/mL)

Change in C-reactive protein level (ng/mL)

Change in Tumor necrosis factor alpha (TNF-α) level

TNF-α level in pg/mL.

Change in Salivary cortisol (microgram/dL) level

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.

Full Information

NCT ID

NCT04117074

First Posted

October 3, 2019

Last Updated

June 16, 2023

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

Pacira Pharmaceuticals, Inc

1. Study Identification

Unique Protocol Identification Number

NCT04117074

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Recruiting

Study Start Date

April 14, 2021 (Actual)

Primary Completion Date

September 2024 (Anticipated)

Study Completion Date

September 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

Pacira Pharmaceuticals, Inc

4. Oversight

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

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Surgery, Analgesia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm 1: Thoracic Epidural Analgesia with bupivicaine

Arm Type

Experimental

Arm Description

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.

Arm Title

Arm 2: Surgical Site Infiltration with Liposomal Bupivacaine

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Liposomal bupivacaine

Other Intervention Name(s)

Exparel

Intervention Description

Surgical site infiltration with 20 mL liposomal bupivacaine prior to laparotomy closure.

Intervention Type

Other

Intervention Name(s)

Thoracic epidural analgesia (bupivacaine)

Intervention Description

Perioperative bupivacaine based thoracic epidural placed preoperatively.

Primary Outcome Measure Information:

Title

Analgesia as assessed by pain intensity scores on a visual analog scale

Description

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.

Time Frame

0 to 48 hours postoperatively

Title

Total opioid consumption

Description

Total opioid consumption in IV mg morphine equivalents from 0 to 48 hours postoperatively will be compared between the two arms.

Time Frame

0 to 48 hours postoperatively

Secondary Outcome Measure Information:

Title

Change in Patient-perceived quality of recovery as assessed by the Quality of Recovery-15 instrument (QoR-15)

Description

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.

Time Frame

Days 1 through 7 post-intervention

Title

Time (days) to return of bowel function (ROBF)

Description

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.

Time Frame

Up to 7 days post-intervention

Title

Number of participants with postoperative ileus

Description

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.

Time Frame

Up to 7 days post-intervention

Title

Mobility as assessed by the Johns Hopkins Highest Level of Mobility (JH-HLM) scale

Description

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.

Time Frame

Up to 7 days post-intervention

Title

Degree of sedation as assessed by the Pasero Opioid-Induced Sedation Scale

Description

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.

Time Frame

Up to 7 days post-intervention

Title

Length of stay

Description

The duration of the index inpatient postoperative admission in days.

Time Frame

Up to 1 year

Title

Time to postoperative diuresis

Description

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.

Time Frame

Arrival in recovery through hospital discharge, up to 1 year

Title

Total intravenous fluids administered in mL

Time Frame

Arrival in recovery through hospital discharge, up to 1 year

Title

Amount of Vasopressor required

Description

Total amount (micrograms) of vasopressor required.

Time Frame

Start of operation through hospital discharge, up to 1 year

Title

Duration of Vasopressor administration

Description

Duration (minutes) of vasopressor administration.

Time Frame

Start of operation through hospital discharge, up to 1 year

Title

Number of postoperative complications

Description

Number of postoperative complications (Maryland Hospital Acquired Conditions).

Time Frame

Day of admission through postoperative day 30

Title

Total direct cost of TEA placement and LB surgical site infiltration

Description

Pharmacy and equipment costs, professional fees and the dollar-value of total OR time required for administration of each intervention will be compared.

Time Frame

Up to 1 year

Title

Post-discharge narcotic utilization

Description

Patient reported total outpatient narcotic use in IV morphine (mg) equivalents on nurse phone survey administered on postoperative day 14.

Time Frame

Postoperative day 14

Title

Change in Serum adrenocorticotropic hormone (ACTH)

Description

Serum ACTH level in pg/mL.

Time Frame