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Completed

NCT Number: NCT04117074

Thoracic Epidural Analgesia vs Surgical Site Infiltration With Liposomal Bupivacaine 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.

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Key information

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 3

Primary location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Liposomal bupivacaine

Drug

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

Other names: Exparel

Thoracic epidural analgesia (bupivacaine)

Other

Perioperative bupivacaine based thoracic epidural placed preoperatively.

Primary outcomes

  1. Analgesia Assessed by the Area Under the Curve of Visual Analog Scale Pain Intensity Scores

    Time frame: 0 to 48 hours postoperatively

    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.

  2. Total Opioid Consumption

    Time frame: 0 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 outcomes

  1. Patient-perceived Quality of Recovery as Assessed by the Quality of Recovery-15 Instrument (QoR-15)

    Time frame: 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 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.

  2. Time (Days) to Return of Bowel Function (ROBF)

    Time frame: 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.

  3. Number of Participants With Postoperative Ileus

    Time frame: Up 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.

  4. Mobility as Assessed by the Johns Hopkins Highest Level of Mobility (JH-HLM) Scale

    Time frame: Up to 7 days post-intervention

    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.

  5. Number of Participants With Sedation Score ≥2 as Assessed by the Pasero Opioid-Induced Sedation Scale

    Time frame: Up 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.

  6. Length of Stay

    Time frame: Up to 1 year

    The duration of the index inpatient postoperative admission in days.

  7. Time to Postoperative Diuresis

    Time frame: Arrival 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.

  8. Total Intravenous Fluids Administered in mL

    Time frame: Arrival in recovery through hospital discharge, up to 1 year

    Total intravenous fluids administered in mL.

  9. Amount of Vasopressor Required

    Time frame: Start of operation through hospital discharge, up to 1 year

    Total amount (micrograms) of Levophed required.

  10. Duration of Vasopressor Administration

    Time frame: Start of operation through hospital discharge, up to 1 year

    Duration (minutes) of vasopressor administration.

  11. Number Participants With Postoperative Complications

    Time frame: Day of admission through postoperative day 30

    Number of participants with postoperative complications (Maryland Hospital Acquired Conditions).

  12. Total Direct Cost of TEA Placement and LB Surgical Site Infiltration

    Time frame: Up to 1 year

    Total Direct Cost (Pharmacy and equipment costs, professional fees and the dollar-value of total OR time required for administration of each intervention)

  13. Post-discharge Narcotic Utilization

    Time frame: Postoperative day 14

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

  14. Number of Participants With 30-day Hospital Readmission

    Time frame: Up to 30 days post discharge from index admission

    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.

Other outcomes

  1. Change in Serum Adrenocorticotropic Hormone (ACTH)

    Time frame: Baseline and postoperative day 7

    Serum ACTH level in pg/mL.

  2. Change in Epinephrine Level (pg/mL)

    Time frame: Baseline and postoperative day 7

  3. Change in Total Cortisol Level (Microgram/dL)

    Time frame: Baseline and postoperative day 7

  4. Change in Anti-diuretic Hormone (ADH) Level

    Time frame: Baseline and postoperative day 7

    ADH level in pg/mL.

  5. Change in Interleukin-6 Level (pg/mL)

    Time frame: Baseline and postoperative day 7

  6. Change in Syndecan-1 Level (pg/mL)

    Time frame: Baseline and postoperative day 7

  7. Change in Atrial Natriuretic Peptide (ANP) Level

    Time frame: Baseline and postoperative day 7

    ANP level in pg/mL.

  8. Change in Glycosaminoglycans Level (ng/mL)

    Time frame: Baseline and postoperative day 7

  9. Change in Endothelial Glycocalyx Constituents (ng/mL)

    Time frame: Baseline and postoperative day 7

  10. Change in C-reactive Protein Level (ng/mL)

    Time frame: Baseline and postoperative day 7

  11. Change in Tumor Necrosis Factor Alpha (TNF-α) Level

    Time frame: Baseline and postoperative day 7

    TNF-α level in pg/mL.

  12. Change in Salivary Cortisol (Microgram/dL) Level

    Time frame: Baseline and postoperative day 7

Sponsors and collaborators

Lead sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Other

Collaborators

  • Pacira Pharmaceuticals, Inc

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2025
Study completion
2025
First posted
Oct 7, 2019
Registry last updated
May 19, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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