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

Phase 4

Completed

Conditions: Malignant Female Reproductive System Neoplasm

Interventions: Procedure: Laparotomy
Drug: Hydromorphone
Other: Questionnaire Administration
Drug: Liposomal Bupivacaine

Registration Number: NCT04258631

Lead Sponsor: Mayo Clinic

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 105

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (laparotomy, liposomal bupivacaine)	Laparotomy	Patients undergo standard of care laparotomy and then receive liposomal bupivacaine.
Arm I (laparotomy, liposomal bupivacaine)	Questionnaire Administration	Patients undergo standard of care laparotomy and then receive liposomal bupivacaine.
Arm II (laparotomy, liposomal bupivacaine, hydromorphone)	Laparotomy	Patients undergo standard of care laparotomy and then receive liposomal bupivacaine and hydromorphone IT.
Arm II (laparotomy, liposomal bupivacaine, hydromorphone)	Liposomal Bupivacaine	Patients undergo standard of care laparotomy and then receive liposomal bupivacaine and hydromorphone IT.
Arm II (laparotomy, liposomal bupivacaine, hydromorphone)	Questionnaire Administration	Patients undergo standard of care laparotomy and then receive liposomal bupivacaine and hydromorphone IT.
Arm I (laparotomy, liposomal bupivacaine)	Liposomal Bupivacaine	Patients undergo standard of care laparotomy and then receive liposomal bupivacaine.
Arm II (laparotomy, liposomal bupivacaine, hydromorphone)	Hydromorphone	Patients undergo standard of care laparotomy and then receive liposomal bupivacaine and hydromorphone IT.

Primary Outcome Measures

Name	Time	Method
Overall Benefit of Analgesia Score (OBAS)	Up to 24 hours after surgery	The Overall Benefit of Analgesia Score (OBAS) is a multi-dimensional survey that measures a patient's benefit from postoperative pain therapy. It assesses pain intensity, opioid-related adverse events, and patient satisfaction with analgesia. Each of 7 questions are scored on a scale from 0 to 4 where 0=minimal/not at all and 4=maximum/very much. The total score is a sum of the 7 item scores with question 7 scored as 4 minus the patient reported number. Total scores range from 0 to 28 with lower scores representing greater benefit from analgesic therapy. The median total OBAS score for each group is presented.

Secondary Outcome Measures

Name	Time	Method
Length of Stay	Up to 1 week after surgery	Length of associated hospitalization in days.
Additional Fluid Requirement After 24 Hours of Surgery	Up to 24 hours after surgery	Number of patients requiring additional IV fluids after surgery.
Weight Gain Following Surgery	Up to 24 hours after surgery	Weight difference post- and pre-surgery.
Total Cost of Care	Entire hospitalization, approximately 2-5 days	All medical costs occurring during hospitalization.
Incidence of Adverse Events	Up to 24 hours after surgery	Reported as the number participants reporting one or more adverse events on each study arm.
Operating Room Time	Approximately 8 hours	Length of time from when the patient entered the operating room to when they left.
Surgical Time	Approximately 8 hours	Time from first incision to surgical site closure.
Pain Management	Whole hospitalization, approximately 2-5 days	Pharmaceutical costs associated with pain management.
Cumulative 24-hour Narcotic Consumption	Up to 24 hours after surgery	Various narcotic medications are standardized and reported as Morphine Milligram Equivalents (MME).
Post-operative Pain Scores	Up to 24 hours after surgery	Postoperative pain is scored on a scale of 0 - 10, with the lower score showing a better outcome.
Time to First Analgesic Request	Up to 24 hours after surgery	Amount of time from leaving surgery to the first request for pain relief.
Use of Intravenous (IV) Patient-controlled Analgesia	Up to 24 hours after surgery	Number of patients that used IV, patient controlled analgesia after surgery.
Use of Intravenous Rescue Opioids	Up to 24 hours after surgery	Number of patients that needed IV rescue opioids after surgery.