TINGLE: Intraoperative TAP Block With Bupivacaine/Dexamethasone Against Liposomal Bupivacaine (Exparel®)

• Sponsor: Cedars-Sinai Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT03723447
• Collaborator: (none)
• Enrollment: 102
• Location: 1
• Arms: 2
• Actual Duration (Months): 12.2
• Patients Per Site Per Month: 8.4

Study Details

Study Description

Brief Summary

Traditionally, opioids are heavily utilized in treating postoperative pain but they are associated with numerous side effects. The use of the transversus abdominis plane (TAP) blocks have become standard practice to extend the post-operative analgesic window and limit opioid use. A new liposomal-depo formulation of bupivacaine (Exparel) has gained popularity as a long-lasting TAP block medication, but has not been studied in a well-powered clinical trial specifically in colorectal patients nor compared to a bupivacaine/steroid mixture which may offer similar effects. We conduct a prospective randomized prospective randomized study of patients undergoing major laparoscopic colorectal surgery to compare the analgesic effects of a bupivacaine/steroid mixture versus liposomal bupivacaine.

Condition or Disease	Intervention/Treatment	Phase
Pain, Postoperative; Crohn Disease; Inflammatory Bowel Diseases; Colorectal Cancer; Gastrointestinal Cancer; Gastrointestinal Disease; Digestive System Disease; Pain; Pain, Neuropathic; Intestinal Disease	Drug: Liposomal bupivacaine; Drug: Bupivacaine/epinephrine/dexamethasone	Phase 4

Detailed Description

Postoperative pain can pose significant challenges in the postoperative recovery of patients undergoing major colorectal surgery. Traditionally, opioids have played an important role in treating postoperative pain. It is well established that opioids are highly effective in relieving pain; however, opioids are associated with numerous side effects that include nausea, vomiting, constipation, ileus, bladder dysfunction, respiratory depression, pruritus, drowsiness, sedation, and allergic reaction. These opioid side effects, which range in severity, can significantly interfere with discharge home, particularly following colorectal surgery. Significant interest has grown for the use of guided regional anesthesia, specifically the use of the transversus abdominis plane (TAP) block to extend the post-operative analgesic window and ultimately limit opioid use. While bupivacaine formulations including a steroid has been shown to prolong the anesthetic effects of the regional field block, a new liposomal-depo formulation of bupivacaine (Exparel) has gained popularity and has additionally been shown to provide extended analgesia. Although promising data exists surrounding each modality, liposomal bupivacaine has not been studied in a well-powered clinical trial specifically in colorectal patients nor compared to a bupivacaine/steroid mixture.

We are proposing a prospective randomized study of patients undergoing major laparoscopic colorectal surgery to compare the analgesic effects of a bupivacaine/steroid mixture versus liposomal bupivacaine (Exparel). We hypothesize that the liposomal formulation of bupivacaine will provide superior perioperative pain control at 48 hours post-operation measured by total consumed oral morphine equivalents. In addition, we will measure postoperative pain scores, time until ambulation, antiemetic use, length of postoperative hospital stay, postoperative ileus, and adverse events directly related or unrelated to TAP block in the 30-day postoperative period between the three groups.

Study Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective Randomized Trial of Transversus Abdominis Plane (TAP) INtraoperative Block With Bupivacaine/Dexamethasone aGainst Liposomal Bupivacaine (Exparel®): the TINGLE Trial
• Actual Study Start Date: Oct 23, 2018
• Actual Primary Completion Date: Oct 29, 2019
• Actual Study Completion Date: Oct 29, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Bupivacaine/epinephrine/dexamethasone TAP block For the bupivacaine/epinephrine/dexamethasone treatment arm, a standard weight-based dose of bupivacaine and epinephrine combined with 8mg dexamethasone will be administered.	Drug: Bupivacaine/epinephrine/dexamethasone; Bupivacaine/epinephrine/dexamethasone will be given during the bilateral laparoscopic-guided TAP block administered to each patient intraoperatively.; Other Names: Decadron
Active Comparator: Liposomal bupivacaine TAP block For the liposomal bupivacaine treatment arm, 266mg liposomal bupivacaine (Exparel) will be administered.	Drug: Liposomal bupivacaine; Liposomal bupivacaine will be given during the bilateral laparoscopic-guided TAP block given to each patient intraoperatively.; Other Names: Exparel

Outcome Measures

Primary Outcome Measures

1. Cumulative 48-hour Post Surgical Opiate Use (Oral Morphine Equivalent) [48-hours]

Secondary Outcome Measures

1. Post-op Pain Score (Visual Analog Scale) [72-hours post-surgery]

   Visual pain scale recordings will be totaled and averaged during the first 72-hours post-surgery. Visual analog scale is determined by nursing staff when assessing pain scores. Scores range from 0-10 with 10 being the most pain. These values are typically interpreted by nursing staff as mild, moderate, or severe pain and pain medication is given accordingly.

2. Bowel Motility [72 hours post-surgery]

   Time till first bowel movement

3. Postoperative Length of Stay [30 days post-surgery]

   Time from operation until hospital discharge

4. Postoperative Complications [30 days post-surgery]

   Medical or surgical complications measured by Clavien-Dindo classification Clavien-Dindo grade I: any deviation from normal postoperative course no pharmacological or surgical treatment, endoscopic, or radiological interventions were required. Acceptable therapeutic regiments are drugs such as anti-emetics, antipyretics, analgesics, diuretics, and electrolytes. Wound infections or small abscess requiring incision at bedside is within this category Clavien-Dindo grade II: Normal course altered Pharacological management other than in grade 1. Blood transfusions and total parenteral nutrition are also included. Clavien-Dindo grade III: complications that require intervention of various degrees management of these complications require an intervention under local anesthesia or general or epidural anesthesia Clavien-Dindo grade IV: complications threatening the life of a patient manifesting in organ dysfunction, including dialysis

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or Female

2. Undergoing major laparoscopic colorectal procedure

3. Willingness and ability to sign an informed consent document

4. No allergies to anesthetic or analgesic medications

5. ASA physical status Class I - III

6. Aged 18-90 years

Exclusion Criteria:

1. Refusal to participate in the study

2. Age <18 or > 90 years

3. Pregnancy

4. Contraindications to regional anesthetic including but not limited to:

5. Patient refusal to regional field blockade

6. Allergy

7. Infection at the site of needle insertion

8. Systemic infection

9. Bleeding diathesis or coagulopathy (as diagnosed by history or laboratory evaluation)

10. Liver or renal disease (SCr > 1.5)

11. Chronic opioid use

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars Sinai Medical Center	Los Angeles	California	United States	90048

Sponsors and Collaborators

• Cedars-Sinai Medical Center

Investigators

• Principal Investigator: Karen Zaghiyan, MD, Cedars Sinai

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 23, 2018

More Information

Publications

• Knudson RA, Dunlavy PW, Franko J, Raman SR, Kraemer SR. Effectiveness of Liposomal Bupivacaine in Colorectal Surgery: A Pragmatic Nonsponsored Prospective Randomized Double Blinded Trial in a Community Hospital. Dis Colon Rectum. 2016 Sep;59(9):862-9. doi: 10.1097/DCR.0000000000000648.
• Mujukian A, Truong A, Tran H, Shane R, Fleshner P, Zaghiyan K. A Standardized Multimodal Analgesia Protocol Reduces Perioperative Opioid Use in Minimally Invasive Colorectal Surgery. J Gastrointest Surg. 2020 Oct;24(10):2286-2294. doi: 10.1007/s11605-019-04385-9. Epub 2019 Sep 12.
• Truong A, Mujukian A, Fleshner P, Zaghiyan K. No Pain, More Gain: Reduced Postoperative Opioid Consumption with a Standardized Opioid-Sparing Multimodal Analgesia Protocol in Opioid-Tolerant Patients Undergoing Colorectal Surgery. Am Surg. 2019 Oct 1;85(10):1155-1158.

• Responsible Party: Karen Zaghiyan, Surgeon Investigator, Cedars-Sinai Medical Center
• ClinicalTrials.gov Identifier: NCT03723447
• Other Study ID Numbers: Pro00053363
• First Posted: Oct 29, 2018
• Last Update Posted: Feb 17, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by Karen Zaghiyan, Surgeon Investigator, Cedars-Sinai Medical Center: transversus abdominis plane block; tap block; liposomal bupivacaine; exparel; dexamethasone; colorectal surgery; regional anesthesia; bupivacaine; surgery; postoperative pain; pain
• Additional relevant MeSH terms: Gastrointestinal Neoplasms; Crohn Disease; Intestinal Diseases; Inflammatory Bowel Diseases; Gastrointestinal Diseases; Digestive System Diseases; Neuralgia; Pain, Postoperative; Dexamethasone; Epinephrine; Bupivacaine

Study Results

Participant Flow

Pre-assignment Detail	One patient was noted to have chronic opioid use discovered after randomization. They were subsequently excluded from analysis

Arm/Group Title	Bupivacaine/Epinephrine/Dexamethasone TAP Block	Liposomal Bupivacaine TAP Block
Arm/Group Description	For the bupivacaine/epinephrine/dexamethasone treatment arm, a standard weight-based dose of bupivacaine and epinephrine combined with 8mg dexamethasone will be administered. Bupivacaine/epinephrine/dexamethasone: Bupivacaine/epinephrine/dexamethasone will be given during the bilateral laparoscopic-guided TAP block administered to each patient intraoperatively.	For the liposomal bupivacaine treatment arm, 266mg liposomal bupivacaine (Exparel) will be administered. Liposomal bupivacaine: Liposomal bupivacaine will be given during the bilateral laparoscopic-guided TAP block given to each patient intraoperatively.
Period Title: Overall Study
STARTED	50	51
COMPLETED	50	51
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Bupivacaine/Epinephrine/Dexamethasone TAP Block	Liposomal Bupivacaine TAP Block	Total
Arm/Group Description	For the bupivacaine/epinephrine/dexamethasone treatment arm, a standard weight-based dose of bupivacaine and epinephrine combined with 8mg dexamethasone will be administered. Bupivacaine/epinephrine/dexamethasone: Bupivacaine/epinephrine/dexamethasone will be given during the bilateral laparoscopic-guided TAP block administered to each patient intraoperatively.	For the liposomal bupivacaine treatment arm, 266mg liposomal bupivacaine (Exparel) will be administered. Liposomal bupivacaine: Liposomal bupivacaine will be given during the bilateral laparoscopic-guided TAP block given to each patient intraoperatively.	Total of all reporting groups
Overall Participants	50	51	101
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	42	42	42
Sex: Female, Male (Count of Participants)
Female	29 58%	22 43.1%	51 50.5%
Male	21 42%	29 56.9%	50 49.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 10%	1 2%	6 5.9%
Not Hispanic or Latino	31 62%	32 62.7%	63 62.4%
Unknown or Not Reported	14 28%	18 35.3%	32 31.7%
Region of Enrollment (participants) [Number]
United States	50 100%	51 100%	101 100%

Outcome Measures

1. Primary Outcome

Title	Cumulative 48-hour Post Surgical Opiate Use (Oral Morphine Equivalent)
Time Frame	48-hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupivacaine/Epinephrine/Dexamethasone TAP Block	Liposomal Bupivacaine TAP Block
Arm/Group Description	For the bupivacaine/epinephrine/dexamethasone treatment arm, a standard weight-based dose of bupivacaine and epinephrine combined with 8mg dexamethasone will be administered. Bupivacaine/epinephrine/dexamethasone: Bupivacaine/epinephrine/dexamethasone will be given during the bilateral laparoscopic-guided TAP block administered to each patient intraoperatively.	For the liposomal bupivacaine treatment arm, 266mg liposomal bupivacaine (Exparel) will be administered. Liposomal bupivacaine: Liposomal bupivacaine will be given during the bilateral laparoscopic-guided TAP block given to each patient intraoperatively.
Measure Participants	50	51
Median (Inter-Quartile Range) [Oral morphine equivalents]	47	69

2. Secondary Outcome

Title	Post-op Pain Score (Visual Analog Scale)
Description	Visual pain scale recordings will be totaled and averaged during the first 72-hours post-surgery. Visual analog scale is determined by nursing staff when assessing pain scores. Scores range from 0-10 with 10 being the most pain. These values are typically interpreted by nursing staff as mild, moderate, or severe pain and pain medication is given accordingly.
Time Frame	72-hours post-surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupivacaine/Epinephrine/Dexamethasone TAP Block	Liposomal Bupivacaine TAP Block
Arm/Group Description	For the bupivacaine/epinephrine/dexamethasone treatment arm, a standard weight-based dose of bupivacaine and epinephrine combined with 8mg dexamethasone will be administered. Bupivacaine/epinephrine/dexamethasone: Bupivacaine/epinephrine/dexamethasone will be given during the bilateral laparoscopic-guided TAP block administered to each patient intraoperatively.	For the liposomal bupivacaine treatment arm, 266mg liposomal bupivacaine (Exparel) will be administered. Liposomal bupivacaine: Liposomal bupivacaine will be given during the bilateral laparoscopic-guided TAP block given to each patient intraoperatively.
Measure Participants	50	51
Median (Inter-Quartile Range) [score on a scale]	4	4

3. Secondary Outcome

Title	Bowel Motility
Description	Time till first bowel movement
Time Frame	72 hours post-surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupivacaine/Epinephrine/Dexamethasone TAP Block	Liposomal Bupivacaine TAP Block
Arm/Group Description	For the bupivacaine/epinephrine/dexamethasone treatment arm, a standard weight-based dose of bupivacaine and epinephrine combined with 8mg dexamethasone will be administered. Bupivacaine/epinephrine/dexamethasone: Bupivacaine/epinephrine/dexamethasone will be given during the bilateral laparoscopic-guided TAP block administered to each patient intraoperatively.	For the liposomal bupivacaine treatment arm, 266mg liposomal bupivacaine (Exparel) will be administered. Liposomal bupivacaine: Liposomal bupivacaine will be given during the bilateral laparoscopic-guided TAP block given to each patient intraoperatively.
Measure Participants	50	51
Median (Inter-Quartile Range) [days]	1	1

4. Secondary Outcome

Title	Postoperative Length of Stay
Description	Time from operation until hospital discharge
Time Frame	30 days post-surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupivacaine/Epinephrine/Dexamethasone TAP Block	Liposomal Bupivacaine TAP Block
Arm/Group Description	For the bupivacaine/epinephrine/dexamethasone treatment arm, a standard weight-based dose of bupivacaine and epinephrine combined with 8mg dexamethasone will be administered. Bupivacaine/epinephrine/dexamethasone: Bupivacaine/epinephrine/dexamethasone will be given during the bilateral laparoscopic-guided TAP block administered to each patient intraoperatively.	For the liposomal bupivacaine treatment arm, 266mg liposomal bupivacaine (Exparel) will be administered. Liposomal bupivacaine: Liposomal bupivacaine will be given during the bilateral laparoscopic-guided TAP block given to each patient intraoperatively.
Measure Participants	50	51
Median (Inter-Quartile Range) [days]	3	3

5. Secondary Outcome

Title	Postoperative Complications
Description	Medical or surgical complications measured by Clavien-Dindo classification Clavien-Dindo grade I: any deviation from normal postoperative course no pharmacological or surgical treatment, endoscopic, or radiological interventions were required. Acceptable therapeutic regiments are drugs such as anti-emetics, antipyretics, analgesics, diuretics, and electrolytes. Wound infections or small abscess requiring incision at bedside is within this category Clavien-Dindo grade II: Normal course altered Pharacological management other than in grade 1. Blood transfusions and total parenteral nutrition are also included. Clavien-Dindo grade III: complications that require intervention of various degrees management of these complications require an intervention under local anesthesia or general or epidural anesthesia Clavien-Dindo grade IV: complications threatening the life of a patient manifesting in organ dysfunction, including dialysis
Time Frame	30 days post-surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bupivacaine/Epinephrine/Dexamethasone TAP Block	Liposomal Bupivacaine TAP Block
Arm/Group Description	For the bupivacaine/epinephrine/dexamethasone treatment arm, a standard weight-based dose of bupivacaine and epinephrine combined with 8mg dexamethasone will be administered. Bupivacaine/epinephrine/dexamethasone: Bupivacaine/epinephrine/dexamethasone will be given during the bilateral laparoscopic-guided TAP block administered to each patient intraoperatively.	For the liposomal bupivacaine treatment arm, 266mg liposomal bupivacaine (Exparel) will be administered. Liposomal bupivacaine: Liposomal bupivacaine will be given during the bilateral laparoscopic-guided TAP block given to each patient intraoperatively.
Measure Participants	50	51
None	29 58%	32 62.7%
Clavien-Dindo grade I	7 14%	2 3.9%
Clavien-Dindo grade II	8 16%	7 13.7%
Clavien-Dindo grade III	6 12%	10 19.6%

Adverse Events

Time Frame	Data was collected for each patient for a maximum period of 3 months postoperatively.
Adverse Event Reporting Description	Adverse events are defined by complications or unexpected sequelae as a result of TAP block administration
Arm/Group Title	Bupivacaine/Epinephrine/Dexamethasone TAP Block		Liposomal Bupivacaine TAP Block
Arm/Group Description	For the bupivacaine/epinephrine/dexamethasone treatment arm, a standard weight-based dose of bupivacaine and epinephrine combined with 8mg dexamethasone will be administered. Bupivacaine/epinephrine/dexamethasone: Bupivacaine/epinephrine/dexamethasone will be given during the bilateral laparoscopic-guided TAP block administered to each patient intraoperatively.		For the liposomal bupivacaine treatment arm, 266mg liposomal bupivacaine (Exparel) will be administered. Liposomal bupivacaine: Liposomal bupivacaine will be given during the bilateral laparoscopic-guided TAP block given to each patient intraoperatively.
All Cause Mortality
	Bupivacaine/Epinephrine/Dexamethasone TAP Block		Liposomal Bupivacaine TAP Block
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/51 (0%)
Serious Adverse Events
	Bupivacaine/Epinephrine/Dexamethasone TAP Block		Liposomal Bupivacaine TAP Block
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/51 (0%)
Other (Not Including Serious) Adverse Events
	Bupivacaine/Epinephrine/Dexamethasone TAP Block		Liposomal Bupivacaine TAP Block
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		0/51 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.