EXPAREL Post-tonsillectomy Clinical Trial (EXPCT)

Randomized Clinical Trial Examining Use of Adjunct EXPAREL for Post-tonsillectomy Pain Management in Adults

Tonsillectomy is one of the most commonly performed surgical procedures in the United States. The primary indications for tonsillectomy in the adult population include recurrent pharyngitis, chronic tonsillitis, and obstructive pathology. Tonsillectomy is often associated with severe postoperative pain, which can result in prolonged poor oral intake, dehydration, and the need for high dose narcotics. In severely dehydrated patients, epithelial shedding and necrosis of soft tissues at the surgical site can lead to postoperative complications such as bleeding, delayed healing, and severe pain. The goal for this study is to explore the use of a long acting local anesthetic bupivacaine liposome injectable suspension (Exparel) to manage pain experienced by adult patients after tonsillectomy

Study Overview

• Status: Recruiting
• Conditions: Tonsillectomy
• Intervention / Treatment: Drug: Adjunct Exparel (bupivacaine liposome suspension 1.3%); Other: Standard Care

Detailed Description

The proposed investigation will examine whether Exparel (bupivacaine liposome injectable suspension 1.3%-13.3 mg/mL) when used as a post-excision adjunct to the standard of care bupivacaine HCl 0.25% (2.5 mg/mL) with Epinephrine (5mcg/mL), will decrease the patient's post-tonsillectomy experience of pain intensity, especially for the first three days after surgery, and correspondingly reduce the requirement for pain medications and improve outcomes.

• Study Type: Interventional
• Enrollment (Anticipated): 38
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Paul T Hoff, MD; Phone Number: 734-712-7509; Email: Paul.Hoff@stjoeshealth.org

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Recruiting
      • St. Joseph Mercy Ann Arbor
      • Contact: Paul T Hoff, MD; Phone Number: 734-712-7509; Email: Paul.Hoff@stjoeshealth.org
    • Ypsilanti, Michigan, United States, 48197
      • Recruiting
      • Michigan Otolaryngology Surgery Associates
      • Contact: Paul T. Hoff, MD; Phone Number: 734-712-7509; Email: Paul.Hoff@stjoeshealth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Scheduled to undergo bilateral palatine tonsillectomy as the only procedure
2. Adults age 18 years and older.

Exclusion Criteria:

1. Severe systemic disease that is clinically significant in the judgement of the investigator.
2. Coagulation disorder that is clinically significant in the judgement of the investigator.
3. Current or previous history of analgesic dependence
4. Allergy to any of the drugs used in the study (bupivacaine)
5. Women known to be pregnant, planning to become pregnant, or lactating
6. Hearing impairment that is clinically significant in the judgement of the investigator.
7. Cardiovascular disease that is clinically significant in the judgement of the investigator.
8. Impaired liver function that is clinically significant in the judgement of the investigator.
9. Impaired renal function that is clinically significant in the judgement of the investigator.
10. Unable to provide consent.
11. Additional surgical procedures planned concurrently with palatine tonsillectomy.
12. Planned use of topical or injected anesthetics other than those administered by the study within the two week follow up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adjunct Exparel; After removal of the tonsils and before extubation, the principal investigator will infiltrate 0.5 mL of the standard of care medication-bupivacaine HCl 0.25% (2.5 mg/mL) with epinephrine (5 mcg/mL) i.m.-into the upper and lower poles of the anterior and posterior tonsillar pillars on the right and left side of the oropharynx for a volume of 2 mL of bupivacaine HCl on each side. Following the standard medication, the principal investigator will infiltrate 0.5 mL of adjunct Exparel (bupivacaine liposome suspension 1.3% [13.3 mg/mL], i.m.) into the upper and lower poles of the anterior and posterior tonsillar pillars on the right and left side of the oropharynx for a volume of 2 mL of bupivacaine liposome injectable suspension on each side.	Drug: Adjunct Exparel (bupivacaine liposome suspension 1.3%); After removal of the tonsils and before extubation, the principal investigator will infiltrate 0.5 mL of the standard of care medication-bupivacaine HCl 0.25% (2.5 mg/mL) with epinephrine (5 mcg/mL) i.m.-into the upper and lower poles of the anterior and posterior tonsillar pillars on the right and left side of the oropharynx for a volume of 2 mL of bupivacaine HCl on each side. Following the standard medication, the principal investigator will infiltrate 0.5 mL of adjunct Exparel (bupivacaine liposome suspension 1.3% [13.3 mg/mL] i.m.) into the upper and lower poles of the anterior and posterior tonsillar pillars on the right and left side of the oropharynx for a volume of 2 mL of bupivacaine liposome injectable suspension 1.3% (13.3 mg/mL) on each side.; Other Names: Bupivacaine liposome suspension 1.3%; Other: Standard Care; After removal of the tonsils and before extubation, the principal investigator will infiltrate 0.5 mL of the standard of care medication-bupivacaine HCl 0.25% (2.5 mg/ mL) with epinephrine (5 mcg/mL) i.m.-into the upper and lower poles of the anterior and posterior tonsillar pillars on the right and left side of the oropharynx for a volume of 2 mL of bupivacaine HCl on each side.; Other Names: Bupivacaine HCl with epinephrine
Other: Standard Care; After removal of the tonsils and before extubation, the principal investigator will infiltrate 0.5 mL of the standard of care medication-bupivacaine HCl 0.25% (2.5 mg/ mL) with epinephrine (5 mcg/mL) i.m.-into the upper and lower poles of the anterior and posterior tonsillar pillars on the right and left side of the oropharynx for a volume of 2 mL of bupivacaine HCl on each side.	Other: Standard Care; After removal of the tonsils and before extubation, the principal investigator will infiltrate 0.5 mL of the standard of care medication-bupivacaine HCl 0.25% (2.5 mg/ mL) with epinephrine (5 mcg/mL) i.m.-into the upper and lower poles of the anterior and posterior tonsillar pillars on the right and left side of the oropharynx for a volume of 2 mL of bupivacaine HCl on each side.; Other Names: Bupivacaine HCl with epinephrine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pain rating between post anesthesia care unit (PACU) baseline and designated post-operative days	Patient reported average and maximum pain rating over a 24-hour period using the St. Joseph Mercy Ann Arbor (SJMAA) standard visual analog 11 point pain rating scale. The minimum value of 0 indicates no pain and the maximum value of 10 indicates the worst possible pain. A higher value represent greater pain and a worse outcome. The baseline pain rating is the maximum rating from PACU on the day of surgery. Day-1 begins at 12:00 AM (after midnight) day of surgery and extends through 11:59 PM. Each following designated day will begin at 12:00 AM and extend through 11:59 PM.	Post-tonsillectomy Days 1, 2, 3, 5, and 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in total amount of prescribed narcotic pain medication taken between Day-1 and designated post-operative days	Patient reported amount of prescribed narcotic pain medication in mg. taken during a 24-hour period. Higher values represent greater amounts of narcotic pain medication consumed and a worse outcome. Day-1 begins at 12:00 AM (midnight after the day of surgery and extends through 11:59 PM. Day-2 and each following designated day will begin at 12:00 AM and will extend through 11:59 PM.	Post-tonsillectomy Days 1, 2, 3, 5, and 10
Change in the total amount of over the counter pain medication taken between Day-1 and designated post-operative days	Patient reported amount of over the counter pain medication taken in mg during a 24-hour period. Higher values represent greater amounts of over the counter pain medication consumed and a worse outcome. Day-1 begins at 12:00 AM (after midnight) day of surgery and will extend through 11:59 PM. Day-2 and each following designated day will begin at 12:00 AM and will extend through 11:59 PM.	Post-tonsillectomy Days 1, 2, 3, 5, and 10

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the amount of fluid intake consumed between Day-1 and designated post-operative days	Patient reported amount of fluid intake in ounces during a 24-hour period. Lower values represent less fluid intake and a worse outcome.	Post-tonsillectomy Days 1, 2, 3, 5, and 10
Time to change in food intake	Patient reported time in days to change in food intake from liquids to other thicker foods such as smoothies, cream soups, puddings, etc., and to solid food such as eggs, mashed vegetables, soft pasta, etc. A longer duration until a change in food intake represents a worse outcome.	Post-tonsillectomy Days 1, 2, 3, 5, and 10
Time to first physical activity outside of the home	Patient reported day of first physical activity outside of the home, such as running an errand. A longer duration until physical activity outside of the home represents a worse outcome.	Post-tonsillectomy Days 1, 2, 3, 5, and 10
Adverse Event	Patient reported adverse event such as bleeding, Emergency Department visit, return to surgery, allergic reaction, side effects of medication, etc.	Post-tonsillectomy Days 1, 2, 3, 5, and 10

Collaborators and Investigators

• Sponsor: Paul Hoff
• Collaborators: St. Joseph Mercy Ann Arbor

Publications and helpful links

General Publications

• Grainger J, Saravanappa N. Local anaesthetic for post-tonsillectomy pain: a systematic review and meta-analysis. Clin Otolaryngol. 2008 Oct;33(5):411-9. doi: 10.1111/j.1749-4486.2008.01815.x.
• 2. Marcaine™ [package insert]. Hospira, Inc., Lake Forest, IL; October 2011. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022046s004lbl.pdf. Accessed June 12, 2017.
• Bulbake U, Doppalapudi S, Kommineni N, Khan W. Liposomal Formulations in Clinical Use: An Updated Review. Pharmaceutics. 2017 Mar 27;9(2):12. doi: 10.3390/pharmaceutics9020012.
• 1. Exparel® [package insert]. Pacira Pharmaceuticals, Inc., San Diego, CA; 2015. https://www.exparel.com/sites/default/files/EXPAREL_Prescribing_Information.pdf. Accessed June 12, 2017.
• Cullen KA, Hall MJ, Golosinskiy A. Ambulatory surgery in the United States, 2006. Natl Health Stat Report. 2009 Jan 28;(11):1-25.
• Bhattacharyya N, Kepnes LJ. Revisits and postoperative hemorrhage after adult tonsillectomy. Laryngoscope. 2014 Jul;124(7):1554-6. doi: 10.1002/lary.24541. Epub 2014 Jan 3.
• Stelter K, Hiller J, Hempel JM, Berghaus A, Hagedorn H, Andratschke M, Canis M. Comparison of two different local anaesthetic infiltrations for postoperative pain relief in tonsillectomy: a prospective, randomised, double blind, clinical trial. Eur Arch Otorhinolaryngol. 2010 Jul;267(7):1129-34. doi: 10.1007/s00405-009-1200-8. Epub 2010 Jan 13.
• Arikan OK, Ozcan S, Kazkayasi M, Akpinar S, Koc C. Preincisional infiltration of tonsils with ropivacaine in post-tonsillectomy pain relief: double-blind, randomized, placebo-controlled intraindividual study. J Otolaryngol. 2006 Jun;35(3):167-72.
• Diakos EA, Gallos ID, El-Shunnar S, Clarke M, Kazi R, Mehanna H. Dexamethasone reduces pain, vomiting and overall complications following tonsillectomy in adults: a systematic review and meta-analysis of randomised controlled trials. Clin Otolaryngol. 2011 Dec;36(6):531-42. doi: 10.1111/j.1749-4486.2011.02373.x.
• 10. Tamm-Daniels, Inge. Liposomal Bupivacaine: What Is All The Fuss? University of Wisconsin School of Medicine and Public Health Madison, 5 Nov 2014-video Department of Anesthesiology grand Rounds https://videos.med.wisc.edu/videos/56752. Accessed July 10, 2017.
• Tong YC, Kaye AD, Urman RD. Liposomal bupivacaine and clinical outcomes. Best Pract Res Clin Anaesthesiol. 2014 Mar;28(1):15-27. doi: 10.1016/j.bpa.2014.02.001. Epub 2014 Mar 15.

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2018
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: October 17, 2017
• First Submitted That Met QC Criteria: January 26, 2018
• First Posted (Actual): February 5, 2018

Study Record Updates

• Last Update Posted (Actual): May 19, 2021
• Last Update Submitted That Met QC Criteria: May 18, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Pain; Adults
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Adrenergic alpha-Agonists; Adrenergic Agonists; Anesthetics, Local; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Bupivacaine; Epinephrine
• Other Study ID Numbers: HSR-17-1714

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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