Comparing TAP Blocks Bupivacaine, and Placebo for Plane (CLEVELAND)

Comparison of Liposomal Bupivacaine, Plain Bupivacaine, and Placebo for Transversus Abdominis Plane Blocks: A Randomized, Blinded Trial

The study will prospectively compare the analgesic efficacy of TAP blocks with liposomal bupivacaine, plain bupivacaine, and placebo in patients who are scheduled for major abdominal surgery. The primary aim is to assess the duration of the local analgesia (determined by pinprick and cold) in all four quadrants. Comparing opioid consumption and pain scores is a secondary aim. All aims will be assessed over 72 hours or the duration of hospitalization if shorter.

Study Overview

• Status: Recruiting
• Conditions: Abdominal Surgery
• Intervention / Treatment: Drug: Liposomal bupivacaine; Drug: Plain bupivacaine; Drug: Normal saline

Detailed Description

The investigators propose a randomized double-blind trial comparing TAP blocks with liposomal bupivacaine, plain bupivacaine, and placebo in patients having elective abdominal surgery.

After eligibility is confirmed, patients will receive complete information about the study both verbally and in writing. Informed consent will be obtained from the patients prior to randomization and study-specific procedures.

Randomization will be based on computer-generated codes and use random-sized blocks. Allocations will be concealed until the morning of surgery where they will be provided by a web-based system. Randomization will be stratified by study site and chronic opioid use, defined by opioid use for more than 30 consecutive days within three preoperative months, at a daily dose of 15 mg or more of morphine or equivalent. Randomization will also be stratified according to anticipated type of surgery (open vs. laparoscopic-assisted). Clinicians doing the blocks will not be involved in data collection and all the evaluators will be blinded to group allocations.

All blocks will be performed preoperatively or after induction of anesthesia by attending anesthesiologists or regional anesthesia fellows who are experienced in TAP blocks. Premedication will be administered at the discretion of the attending anesthesiologist and standard monitors will be used. Patients will be given 1 g oral acetaminophen an hour before surgery, and an additional 500 mg every 6 hours for 72 hours after surgery starting with oral intake.

Patients will be randomly assigned to: 1) 4-quadrant TAP block with liposomal bupivacaine; 2) 4-quadrant TAP block with plain bupivacaine; or, 3) placebo (normal saline). An in-plane ultrasound will be guide TAP blocks. Two subcostal injections will be applied by placing the probe midline and then moving lateral along the subcostal margin identifying area between the rectus abdominis sheath and the transversus abdominis muscle. The lateral two TAP block injections will be applied in the midaxillary line between the thoracic cage and iliac crest between external oblique and transversus abdominis muscles. Once the target area is positioned, the following injections will be given, based on randomization:

Liposomal bupivacaine. 40 ml of plain bupivacaine 0.25% will be mixed with 20 ml liposomal bupivacaine and 20 ml of saline. 20 ml of the mix will be injected at each location of the 4-quadrant TAP block.

Plain bupivacaine group. 50 ml of plain bupivacaine 0.5% will be combined with 30 ml of normal saline making a total of 80 ml. 20 ml will be injected at each location of the 4-quadrant TAP block.

Placebo group; patients will receive total of 80 ml of normal saline, injected 20 ml in each of the four-quadrant sites.

General anesthesia will be induced using propofol or etomidate, fentanyl, and rocuronium to facilitate intubation. Anesthesia will be maintained with sevoflurane or isoflurane, along with opioids and muscle relaxants as clinically indicated. However, intraoperative analgesic use will be limited to fentanyl, a short-acting opioid.

Postoperatively, patients will be given intravenous patient-controlled analgesia and nurses will be free to give additional opioid as clinically indicated. Hydromorphone will be the default drug, but fentanyl will be substituted if necessary. Clinicians blinded to trial drug will adjust analgesic management as necessary in an effort to keep verbal response pain scores (details below) <4 points on a 0-10 scale, with 10 being worst pain. When patients no longer need PCA, they will be switched to as-needed hydromorphone or fentanyl.

A single dose of dexamethasone (4-8 mg) will be permitted for PONV prophylaxis, and inhaled steroids will be permitted as necessary to treat reactive airway disease. The use of non-steroidal anti-inflammatory drugs and gabapentinoids will be allowed as part of the ERAS approach (enhanced recovery after surgery) according to hospital's clinical practice. Other opioid-sparing medications such as ketamine and lidocaine patches will not be permitted through the initial 72 postoperative hours.

Patients will be allowed to receive prophylactic anti-emetic (first choice ondansetron) intraoperatively based on the risk assessment for nausea and vomiting. Postoperative anti-emetics for symptomatic treatment will also be allowed; again ondansetron will be the first choice.

• Study Type: Interventional
• Enrollment (Estimated): 237
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Alparslan Turan, MD; Phone Number: 216-445-9857; Email: turana@ccf.org
• Study Contact Backup: Name: Fabio Rodriguez, MD; Phone Number: 216-444-9950; Email: rodrigf3@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: Hani Essber, MD; Phone Number: 216-444-9950; Email: essberh@ccf.org
      • Contact: Roberta Johnson; Phone Number: 216-444-9950; Email: johnsor13@ccf.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent;
• 18-85 years old;
• ASA Physical Status 1-3;
• Scheduled for elective open or laparoscopic-assisted abdominal surgery;
• Anticipated hospitalization of at least three nights;
• Expected requirement for parenteral opioids for at least 72 hours for postoperative pain;
• Able to use IV PCA systems.

Exclusion Criteria:

• Hepatic disease, e.g. twice the normal levels of liver enzymes;
• Kidney disease, e.g. twice the normal level of serum creatinine;
• Bupivacaine sensitivity or known allergy;
• Women who are pregnant or breastfeeding;
• Anticoagulants considered to be a contraindication for TAP blocks;
• Surgeries with high port sites;
• Weight <50 kg.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: liposomal bupivacaine; 40 ml of plain bupivacaine 0.25% will be mixed with 20 ml liposomal bupivacaine and 20 ml of saline. 20 ml of the mix will be injected at each location of the 4-quadrant TAP block.	Drug: Liposomal bupivacaine; 4-quadrant TAP block with liposomal bupivacaine
Active Comparator: plain bupivacaine; 50 ml of plain bupivacaine 0.5% will be combined with 30 ml of normal saline making a total of 80 ml. 20 ml will be injected at each location of the 4-quadrant TAP block.	Drug: Plain bupivacaine; 4-quadrant TAP block with plain bupivacaine
Placebo Comparator: Normal Saline; patients will receive total of 80 ml of normal saline, injected 20 ml in each of the four-quadrant sites.	Drug: Normal saline; placebo (normal saline).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to return of sensation	The investigator evaluate when patients feels both ice and pinprick in at least 6 of the 8 designated test locations, or 75% of the covered points if the TAP block did not initially cover all eight locations.	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid Consumption	The investigators will compare the 3 randomized groups on opioid consumption over the first 72 hours	72 hours

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Alparslan Turan, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2021
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: December 22, 2020
• First Submitted That Met QC Criteria: December 22, 2020
• First Posted (Actual): December 28, 2020

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: 20-790

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