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

Malignant Female Reproductive System Neoplasm Clinical Trial

Official title:

Wound Infiltration With Liposomal Bupivacaine With or Without Intrathecal Analgesia in Laparotomy for Gynecological Malignancy: A Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04258631
• Other study ID #: MC2061
• Secondary ID: NCI-2020-0060919
• Status: Completed
• Phase: Phase 4
• Start date: July 9, 2020
• Est. completion date: May 8, 2023

Study information

• Verified date: May 2023
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: May 8, 2023
• Est. primary completion date: May 8, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Genital Neoplasms, Female
• Malignant Female Reproductive System Neoplasm

Intervention

Drug:
• Hydromorphone
Given IT

Procedure:
• Laparotomy
Undergo laparotomy

Drug:
• Liposomal Bupivacaine
Drug

Other:
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Quality of Recovery-15	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.	At 24 hours after surgery
Primary	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.	Up to 24 hours after surgery
Secondary	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.	Up to 24 hours after surgery
Secondary	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.	Up to 24 hours after surgery
Secondary	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.	Up to 24 hours after surgery
Secondary	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.	Up to 24 hours after surgery
Secondary	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.	Up to 24 hours after surgery
Secondary	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.	Up to 24 hours after surgery
Secondary	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.	Up to 24 hours after surgery
Secondary	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.	Up to 24 hours after surgery
Secondary	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.	Up to 24 hours after surgery
Secondary	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.	Up to 24 hours after surgery
Secondary	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.	Up to 24 hours after surgery
Secondary	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.	Up to 24 hours after surgery
Secondary	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.	Up to 24 hours after surgery