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

Study Overview
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Brief Summary
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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
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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).

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

Conditions
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Malignant Female Reproductive System Neoplasm

Intervention / Treatment
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* Drug: Hydromorphone
* Procedure: Laparotomy
* Drug: Liposomal Bupivacaine
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I (laparotomy, liposomal bupivacaine)<br>Patients undergo standard of care laparotomy and then receive liposomal bupivacaine. | Procedure: Laparotomy<br>* Undergo laparotomy<br>Drug: Liposomal Bupivacaine<br>* Drug<br>* Other names: Exparel;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Arm II (laparotomy, liposomal bupivacaine, hydromorphone)<br>Patients undergo standard of care laparotomy and then receive liposomal bupivacaine and hydromorphone IT. | Drug: Hydromorphone<br>* Given IT<br>* Other names: Hydromorphon;Procedure: Laparotomy<br>* Undergo laparotomy<br>Drug: Liposomal Bupivacaine<br>* Drug<br>* Other names: Exparel;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 |