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

Phase 3
Completed
Conditions
Analgesia
Surgery
Interventions
Other: Thoracic epidural analgesia (bupivacaine)
Registration Number
NCT04117074
Lead Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
106
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 2: Surgical Site Infiltration with Liposomal BupivacaineLiposomal bupivacaineLiposomal 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.
Arm 1: Thoracic Epidural Analgesia with bupivicaineThoracic epidural analgesia (bupivacaine)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.
Primary Outcome Measures
NameTimeMethod
Analgesia as assessed by pain intensity scores on a visual analog scale0 to 48 hours postoperatively

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 consumption0 to 48 hours postoperatively

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

Secondary Outcome Measures
NameTimeMethod
Amount of Vasopressor requiredStart of operation through hospital discharge, up to 1 year

Total amount (micrograms) of vasopressor required.

Change in Patient-perceived quality of recovery as assessed by the Quality of Recovery-15 instrument (QoR-15)Days 1 through 7 post-intervention

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.

Duration of Vasopressor administrationStart of operation through hospital discharge, up to 1 year

Duration (minutes) of vasopressor administration.

Post-discharge narcotic utilizationPostoperative day 14

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)Baseline and postoperative day 7

Serum ACTH level in pg/mL.

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 C-reactive protein level (ng/mL)Baseline and postoperative day 7
Mobility as assessed by the Johns Hopkins Highest Level of Mobility (JH-HLM) scaleUp to 7 days post-intervention

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 ScaleUp to 7 days post-intervention

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.

Change in Anti-diuretic hormone (ADH) levelBaseline and postoperative day 7

ADH level in pg/mL.

Change in Glycosaminoglycans level (ng/mL)Baseline and postoperative day 7
Change in Tumor necrosis factor alpha (TNF-α) levelBaseline and postoperative day 7

TNF-α level in pg/mL.

Change in Salivary cortisol (microgram/dL) levelBaseline and postoperative day 7
Total intravenous fluids administered in mLArrival in recovery through hospital discharge, up to 1 year
Change in Interleukin-6 level (pg/mL)Baseline and postoperative day 7
Change in Atrial natriuretic peptide (ANP) levelBaseline and postoperative day 7

ANP level in pg/mL.

Change in Syndecan-1 level (pg/mL)Baseline and postoperative day 7
Change in Endothelial glycocalyx constituents (ng/mL)Baseline and postoperative day 7
Time (days) to return of bowel function (ROBF)Up to 7 days post-intervention

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 ileusUp to 7 days post-intervention

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.

Length of stayUp to 1 year

The duration of the index inpatient postoperative admission in days.

Time to postoperative diuresisArrival in recovery through hospital discharge, up to 1 year

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.

Number of postoperative complicationsDay of admission through postoperative day 30

Number of postoperative complications (Maryland Hospital Acquired Conditions).

Total direct cost of TEA placement and LB surgical site infiltrationUp to 1 year

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

Rate of 30-day hospital readmissionUp to 30 days post discharge from index admission

Rate of 30-day hospital readmission assessed as the number of participants who get readmitted within 30 days of discharge from the initial admission.

Trial Locations

Locations (1)

Johns Hopkins Hospital

🇺🇸

Baltimore, Maryland, United States

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