Four Quadrants Transverse Abdominus Plane (4Q-TAP) Block With Plain and Liposomal Bupivacaine vs. Thoracic Epidermal Analgesia (TEA) in Patients Undergoing Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) on an Enhanced Recovery Pathway

Four Quadrants Transverse Abdominus Plane (4Q-TAP) Block With Plain and Liposomal Bupivacaine vs. Thoracic Epidermal Analgesia (TEA) in Patients Undergoing Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) on an Enhanced Recovery Pathway: A Non-inferiority Randomized Controlled Trial

The goal of this clinical research study is to compare the effects of 4 quadrant TAP block (4Q-TAP block) with the standard-of-care thoracic epidural analgesia (TEA) in patients recovering from cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).

A 4Q-TAP block is also known as an abdominal wall block and TEA is also known as a thoracic epidural. Both are types of anesthetics but are given in different ways. A 4Q-TAP block is when anesthetic injections are given in 4 different parts of the abdomen. A TEA is when an anesthetic injection is given in the space surrounding the spinal cord through your back.

This is an investigational study. The surgery and the levels of anesthetic participant is receiving are standard-of-care. It is investigational to compare 4Q-TAP block with TEA.

Up to 140 participants will be enrolled in this study. All will take part at MD Anderson.

Study Overview

• Status: Completed
• Conditions: Peritoneal Cancer
• Intervention / Treatment: Drug: Local Anesthetic Solution; Drug: Bupivacaine HCl; Drug: Liposomal Bupivacaine

Detailed Description

Baseline Tests:

If participant agrees to take part in this study, within 60 days before participant's surgery:

• Participant will have a physical exam.
• Blood (about 8 teaspoons) will be drawn for routine tests.
• Participant will complete a questionnaire about the quality of recovery. Participant's responses before surgery will be compared to participant's responses after surgery. It should take about 5 minutes to complete.

Study Groups/Procedures:

Participant will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups on the morning of participant's surgery. This is done because no one knows if one study group is better, the same, or worse than the other group.

• If participant is in Group 1, participant will receive standard-of-care TEA before participant goes to sleep.
• If participant is in Group 2, participant will receive the 4Q-TAP block injections after participant is asleep.

If participant is in Group 1, participant will have a catheter placed in participant's back before surgery so that the TEA can be infused. If needed, participant may receive an injection of numbing medication and/or pain medication before the catheter is placed. Participant will sign a separate consent for the placement of the catheter.

If participant is in Group 2, participant will receive up to four (4) injections of 4Q-TAP block directly into different parts of the abdomen. These injections will take place after participant has been given general anesthesia. An ultrasound will be used to guide these injections. Participant will not be awake for these injections.

Both groups will sign a separate consent for the surgery that explains the procedures and the risks. Participant may receive standard drugs during surgery. The study staff can tell participant about the risks of these drugs and how they are given.

For both groups, information about the surgery will be collected while participant is in the operating room.

Post-Surgery:

After surgery, participant will receive standard drugs for pain as needed. Participant will be asked to complete a questionnaire about the quality of participant's recovery on the following days after surgery:

• Days 1-3
• Day 5
• Day 7
• Day 10 and
• Day 30

The questionnaire should take about 5 minutes each time. Participant will complete the questionnaire in person or participant will be called on the phone to complete it if participant has already left the hospital.

On Days 1, 2, and 7 after surgery, blood (about 8 teaspoons each time) will be drawn for routine tests.

After participant leaves the hospital, researchers will collect information from participant's medical record about participant's standard follow-up visits.

Length of Study Participation:

Active participation in this study will be complete 30 days after the surgery.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written Informed consent
2. 18 years old or older
3. American Society of Anesthesiologists physical status (ASA) 1-3
4. Scheduled surgery: open elective CRS-HIPEC
5. Able to complete the QoR 15 questionnaire
6. Patients scheduled to receive intraoperative chemotherapy

Exclusion Criteria:

1. Thrombocytopenia (platelet count: <100,000 cell/dL), coagulopathy (International Normalized Ratio > 1.5, PT>16.5 seconds or aPTT > 35.9 seconds)
2. Bupivacaine or liposomal bupivacaine sensitive or known allergy;
3. Pregnancy or breastfeeding patients
4. Patients with recent (within 60 days preoperatively) history severe hepatic disease (defined as liver injury with encephalopathy plus impaired synthetic liver function (i.e. >1.5)
5. Patients with recent (within 15 days preoperatively) history deteriorate kidney function (creatinine serum concentrations > 2.5 mg/dL or eGFR < 30 mL/kg/min)
6. Chronic opioid use defined as daily opioid use for more than one month prior the scheduled date of surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard-of-Care Thoracic Epidural Analgesia (TEA); An epidural catheter placed before induction of anesthesia by an anesthesiologist. A bolus or infusion of the local anesthetic solution with or without the addition opioids given before surgical incision according to anesthesia provider's clinical judgment.	Drug: Local Anesthetic Solution; A bolus or infusion of local anesthetic solution with or without the addition opioids given before surgical incision according to anesthesia provider's clinical judgment.
Active Comparator: 4Q-TAP Blocks; Participants have an ultrasound guided 4Q-TAP block. A maximum of 80 cc of a solution consisting of 30 mg of bupivacaine HCl in 10 cc of preservative free normal saline (PFNS) and 65 mg of liposomal bupivacaine in 10 cc of PFNS injected before surgical incision in each of the four quadrants.	Drug: Bupivacaine HCl; 30 mg of Bupivacaine HCl in 10 cc of preservative free normal saline (PFNS) injected before surgical incision in each of the four quadrants.; Drug: Liposomal Bupivacaine; 65 mg of Liposomal Bupivacaine in 10 cc of PFNS injected before surgical incision in each of the four quadrants.; Other Names: EXPAREL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of TEA vs 4Q-TAP in QoR at Postoperative Day (POD)2	To compare the efficacy of 4 quadrants TAP blocks (4Q-TAP) versus Thoracic Epidural Analgesia (routine care) on the quality of recovery 48 hours after CRS-HIPEC surgery, measure by QoR-15 changes from Pre-Op to POD2. The QoR scale is a validated scoring system that allows for the quantification of a patient's early postoperative health status. The minimum score 0 and maximum score 150. The higher score mean a better outcome.	48 hours after CRS-HIPEC surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
4Q-TAP Versus TEA on Postoperative Pain	Pain intensity at rest and cough measure using a Validity and Reliability of the Verbal Numerical Rating Scale (VNRS) (0 = no pain - 10 = worst pain ever). Higher numerical scores on the scale indicate more pain, thus a worse outcome. Data reported as time-weighted pain scores from discharge from the PACU until 48 hours after the end of surgery.	48 hours after CRS-HIPEC surgery
Comparison of the Total Opioid Consumption Between Patients With 4Q-TAP Versus TEA	Opioid Consumption reported as morphine equivalents required during the 48 hours after the end of surgery.	During the 48 hours after CRS-HIPEC surgery
Comparison of the Length of Stay (LOS) Between Patients With 4Q-TAP Versus TEA	Length of stay calculated from day of surgery to date of hospital discharge.	Length of stay calculated from day of surgery to date of hospital discharge, up to 46 days
Number of Participants With Adverse Events Related to 4Q-TAP Versus TEA	An adverse event is any symptom, sign, illness, or experience which develops or worsens during the course of the study, whether or not the event is considered related to study drug. Adverse events (AEs) related to the study interventions recorded within the first 48 hours after the end of surgery.	48 hours after CRS-HIPEC surgery
Number of Participants With Incidence of Opioid-Related Adverse Events Related to 4Q-TAP Versus TEA 48	Opioid-related adverse (i.e. respiratory depression, pruritus, sedation, delirium) within the first 48 hours after the end of surgery.	Within the first 48 hours after the end of CRS-HIPEC surgery
Number of Participants With Incidence of Postoperative Complications and Morbidity in Patients Receiving 4Q-TAP Versus TEA	Postoperative complications recorded using Clavien-Dindo scale and POMS.	48 hours after CRS-HIPEC surgery

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: Juan P. Cata, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2017
• Primary Completion (Actual): November 24, 2020
• Study Completion (Actual): November 24, 2020

Study Registration Dates

• First Submitted: November 27, 2017
• First Submitted That Met QC Criteria: November 30, 2017
• First Posted (Actual): December 2, 2017

Study Record Updates

• Last Update Posted (Actual): February 18, 2022
• Last Update Submitted That Met QC Criteria: January 27, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Liposomal Bupivacaine; Peritoneal Cancer; Local Anesthetic Solution; Bupivacaine HCl
• Additional Relevant MeSH Terms: Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Hyperthermia; Fever; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: 2017-0492; NCI-2018-00999 (Other Identifier: NCI)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No