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Liposomal Bupivacaine With or Without Hydromorphone for the Improvement of Pain Control After Laparotomy in Patients With Gynecological Malignancies

Primary Purpose

Malignant Female Reproductive System Neoplasm

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Hydromorphone
Laparotomy
Liposomal Bupivacaine
Questionnaire Administration
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Malignant Female Reproductive System Neoplasm

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Elective surgery for suspected (based on consulting surgeon's opinion-imaging, laboratory [lab], pathology [path]) gynecological malignancy, enhanced recovery after surgery (ERAS) protocol

Exclusion Criteria:

  • Inability to read or understand English
  • Prehospitalization narcotic use if weekly average daily oral morphine equivalent of > 20 mg
  • Chronic pain syndromes such as fibromyalgia
  • Extensive surgery planned (surrogate for post-operative [postop] pain): Planned intensive care unit (ICU) admission, abdominoperineal resection, exenteration, use of intraoperative radiation (IORT), hyperthermic intraperitoneal chemotherapy (HIPEC)

  • Contraindication to neuraxial analgesia:

    • Coagulopathy

      • International normalized ratio (INR) > 1.2 current or predicted after surgery (e.g. planned right hepatic resection)
      • Thrombocytopenia. Platelets (plts) < 100
      • Hemophiliac disease states (hemophilia, von Willebrand disease, etc.)
      • Patients receiving antithrombotic or thrombolytic therapy are excluded according to the American Society of Regional Anesthesia and Pain Medicine (ASRA) guidelines
    • Localized infection at the potential site of injection
    • Significant developmental or structural spinal abnormalities that would preclude a safe spinal technique. These include spina bifida, tethered spinal cord, lumbar spinal fusion, and active lumbar radiculopathy
  • Patients with stage 4 or 5 kidney disease (glomerular filtration rate [GFR] less than 30 ml/min per 1.73 m^2)
  • Intolerance or allergy to opioids, acetaminophen, or amide-type local anesthetics
  • Current pregnancy

Sites / Locations

  • Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm I (laparotomy, liposomal bupivacaine)

Arm II (laparotomy, liposomal bupivacaine, hydromorphone)

Arm Description

Patients undergo standard of care laparotomy and then receive liposomal bupivacaine.

Patients undergo standard of care laparotomy and then receive liposomal bupivacaine and hydromorphone IT.

Outcomes

Primary Outcome Measures

Overall Benefit of Analgesia Score (OBAS)
The mean OBAS score between the two groups will be presented along with the upper limit of the 95% confidence bound for the mean difference. Will conclude non-inferiority if this upper limit is less than the predefined limit for noninferiority. Multivariable regression models will be fit to assess for differences in outcomes if there are unbalanced baseline covariates in the two treatment arms. Each of 7 questions are scored on a scale of 0 - 4 with a lower total score reflecting a better outcome.

Secondary Outcome Measures

Cumulative 24 hour narcotic consumption
Will be measured in morphine metabolic equivalents. Data will be summarized using standard descriptive statistics by reporting mean (standard deviation [SD]) or median (interquartile range [IQR]) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Post-operative pain scores
Post-operative pain scores, including rest and movement, will be measured at 4, 8, 16 and 24 hours after surgery. Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test. Postoperative pain is scored on a scale of 0 - 10, with the lower score showing a better outcome.
Time to first analgesic request
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Use of intravenous (IV) patient-controlled analgesia
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Use of intravenous rescue opioids
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Length of stay
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Additional fluid requirement after 24 hours of surgery
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Weight gain following surgery
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Cost of care
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Incidence of adverse events
Incidence of adverse events related to spinal injection, systemic opioid effects and delayed recovery will be assessed. Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Operating room time
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Surgical time
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Total and pain management related standardized costs
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.

Full Information

First Posted
February 4, 2020
Last Updated
May 19, 2023
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04258631
Brief Title
Liposomal Bupivacaine With or Without Hydromorphone for the Improvement of Pain Control After Laparotomy in Patients With Gynecological Malignancies
Official Title
Wound Infiltration With Liposomal Bupivacaine With or Without Intrathecal Analgesia in Laparotomy for Gynecological Malignancy: A Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
July 9, 2020 (Actual)
Primary Completion Date
May 8, 2023 (Actual)
Study Completion Date
May 8, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase IV trial studies how well liposomal bupivacaine with or without hydromorphone works in improving pain control during the first 24 hours after surgery in patients with gynecological malignancies undergoing laparotomy. Liposomal bupivacaine is routinely infiltrated into the skin surrounding the abdominal incision, and is effective in providing good relief of incisional pain. Hydromorphone is also a type of pain medication that may provide better management of deep abdominal pain. It is not yet known if giving liposomal bupivacaine with or without hydromorphone will work better in improving pain in patients with gynecological malignancies during the first 24 hours after surgery.
Detailed Description
PRIMARY OBJECTIVES: I. Evaluate if no additional intervention is noninferior to intrathecal analgesia (ITA) for postoperative pain experience 24 hours after surgery after laparotomy for gynecological malignancy within an established enhanced recovery pathway which includes incisional liposomal bupivacaine (ILB). II. Evaluate the effect of intrathecal analgesia on patient satisfaction with postoperative analgesia after laparotomy for gynecological malignancy. III. Report the impact of ITA use on cost. IV. Validate the Quality of Recovery (QOR)-15 in our population. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo standard of care laparotomy and then receive liposomal bupivacaine. ARM II: Patients undergo standard of care laparotomy and then receive liposomal bupivacaine and hydromorphone intrathecally (IT).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Female Reproductive System Neoplasm

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
104 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (laparotomy, liposomal bupivacaine)
Arm Type
Active Comparator
Arm Description
Patients undergo standard of care laparotomy and then receive liposomal bupivacaine.
Arm Title
Arm II (laparotomy, liposomal bupivacaine, hydromorphone)
Arm Type
Experimental
Arm Description
Patients undergo standard of care laparotomy and then receive liposomal bupivacaine and hydromorphone IT.
Intervention Type
Drug
Intervention Name(s)
Hydromorphone
Other Intervention Name(s)
(-)-Hydromorphone, Dihydromorphinone, Hydromorphon
Intervention Description
Given IT
Intervention Type
Procedure
Intervention Name(s)
Laparotomy
Intervention Description
Undergo laparotomy
Intervention Type
Drug
Intervention Name(s)
Liposomal Bupivacaine
Other Intervention Name(s)
Bupivacaine Liposome Injectable Suspension, Exparel
Intervention Description
Drug
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Overall Benefit of Analgesia Score (OBAS)
Description
The mean OBAS score between the two groups will be presented along with the upper limit of the 95% confidence bound for the mean difference. Will conclude non-inferiority if this upper limit is less than the predefined limit for noninferiority. Multivariable regression models will be fit to assess for differences in outcomes if there are unbalanced baseline covariates in the two treatment arms. Each of 7 questions are scored on a scale of 0 - 4 with a lower total score reflecting a better outcome.
Time Frame
Up to 24 hours after surgery
Secondary Outcome Measure Information:
Title
Cumulative 24 hour narcotic consumption
Description
Will be measured in morphine metabolic equivalents. Data will be summarized using standard descriptive statistics by reporting mean (standard deviation [SD]) or median (interquartile range [IQR]) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Time Frame
Up to 24 hours after surgery
Title
Post-operative pain scores
Description
Post-operative pain scores, including rest and movement, will be measured at 4, 8, 16 and 24 hours after surgery. Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test. Postoperative pain is scored on a scale of 0 - 10, with the lower score showing a better outcome.
Time Frame
Up to 24 hours after surgery
Title
Time to first analgesic request
Description
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Time Frame
Up to 24 hours after surgery
Title
Use of intravenous (IV) patient-controlled analgesia
Description
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Time Frame
Up to 24 hours after surgery
Title
Use of intravenous rescue opioids
Description
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Time Frame
Up to 24 hours after surgery
Title
Length of stay
Description
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Time Frame
Up to 24 hours after surgery
Title
Additional fluid requirement after 24 hours of surgery
Description
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Time Frame
Up to 24 hours after surgery
Title
Weight gain following surgery
Description
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Time Frame
Up to 24 hours after surgery
Title
Cost of care
Description
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Time Frame
Up to 24 hours after surgery
Title
Incidence of adverse events
Description
Incidence of adverse events related to spinal injection, systemic opioid effects and delayed recovery will be assessed. Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Time Frame
Up to 24 hours after surgery
Title
Operating room time
Description
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Time Frame
Up to 24 hours after surgery
Title
Surgical time
Description
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Time Frame
Up to 24 hours after surgery
Title
Total and pain management related standardized costs
Description
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test.
Time Frame
Up to 24 hours after surgery
Other Pre-specified Outcome Measures:
Title
Quality of Recovery-15
Description
Data will be summarized using standard descriptive statistics by reporting mean (SD) or median (IQR) for continuous variables and frequency and percentages for categorical variables. Continuous variables will be compared between the two treatment arms using the two-sample t-test or the Wilcoxon rank sum test as appropriate. Categorical variables will be compared between the two treatment arms using the chi-square test or the Fisher's exact test. The questionnaire includes 15 items, each scored on a scale of 1 - 10, with a total higher score reflecting better outcomes.
Time Frame
At 24 hours after surgery

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Elective surgery for suspected (based on consulting surgeon's opinion-imaging, laboratory [lab], pathology [path]) gynecological malignancy, enhanced recovery after surgery (ERAS) protocol Exclusion Criteria: Inability to read or understand English Prehospitalization narcotic use if weekly average daily oral morphine equivalent of > 20 mg Chronic pain syndromes such as fibromyalgia Extensive surgery planned (surrogate for post-operative [postop] pain): Planned intensive care unit (ICU) admission, abdominoperineal resection, exenteration, use of intraoperative radiation (IORT), hyperthermic intraperitoneal chemotherapy (HIPEC) Contraindication to neuraxial analgesia: Coagulopathy International normalized ratio (INR) > 1.2 current or predicted after surgery (e.g. planned right hepatic resection) Thrombocytopenia. Platelets (plts) < 100 Hemophiliac disease states (hemophilia, von Willebrand disease, etc.) Patients receiving antithrombotic or thrombolytic therapy are excluded according to the American Society of Regional Anesthesia and Pain Medicine (ASRA) guidelines Localized infection at the potential site of injection Significant developmental or structural spinal abnormalities that would preclude a safe spinal technique. These include spina bifida, tethered spinal cord, lumbar spinal fusion, and active lumbar radiculopathy Patients with stage 4 or 5 kidney disease (glomerular filtration rate [GFR] less than 30 ml/min per 1.73 m^2) Intolerance or allergy to opioids, acetaminophen, or amide-type local anesthetics Current pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sean C Dowdy
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Liposomal Bupivacaine With or Without Hydromorphone for the Improvement of Pain Control After Laparotomy in Patients With Gynecological Malignancies

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