Effect of Bupivacaine-infused Fibrin Sealant Application on Post-tonsillectomy Pain & Hemorrhage

NCT02343263 | Terminated Phase 2 Results

• 1 other identifier: 1501306006
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effect of combining two interventions already in use at some institutions for reducing post-operative pain following tonsillectomy or adenotonsillectomy. The standard of care at most institutions is to leave the tonsillectomy wound bed exposed to heal on its own over one to two weeks. At many institutions, surgeons inject or topically apply local anesthetics such as bupivacaine hydrochloride to the tonsillectomy wound bed to help reduce post-operative pain. At other institutions, surgeons apply a layer of fibrin sealant, which is derived from the proteins that help form blood clots in blood, to the tonsillectomy wound bed in order to cover the site and reduce irritation and exposure of the wound bed. Use of fibrin sealant has the additional benefit of potentially reducing postoperative bleeding (hemorrhage) rates. Both the post-tonsillectomy use of bupivacaine (injection and topical) and the use of topical fibrin sealant application have been studied previously in the scientific literature; some studies show a clear benefit, others show no significant reduction in pain when they are used. No studies have documented harm. The purpose of this study is to evaluate the efficacy of infusing bupivacaine anesthetic into the fibrin sealant prior to application to the tonsillectomy wound bed. In this way, the combined product would function as a sort of "medicated bandaid" covering the painful wound bed and slowly delivering an entirely safe total dose of bupivacaine into the wound bed to reduce post-operative pain. Parents will be provided post-operative pain measurements to complete during the first 10 postoperative days and return to the researchers for data analysis.

Conditions

Pain, Postoperative; Postoperative Hemorrhage

Keywords

Tonsillectomy; Adenotonsillectomy; Pain; Hemorrhage

Outcome Measures

Primary Outcomes (2)

• Postoperative Hemorrhage; Study Terminated Due to FDA Requirement for a Investigational New Drug Application Requirement

  Tonsillectomy (and adenotonsillectomy) are associated with a 3-5% postoperative hemorrhage risk from the tonsillectomy wound beds across the United States; our institution has a calculated average of between 4% - 5%. Parents will be contacted 2 to 3 weeks following their procedure and inquiries about post-operative bleeding will be made. Bleeding \>1 tablespoon or that requires A) presentation to an emergency department, B) admission to a hospital, or C) return to the operating room will be considered significant post-operative hemorrhage. Distinction will also be made between early (\<24 hours after surgery) and late (\>24 hours after surgery) postoperative bleeding. The bleeding risk after 2 weeks from surgery is exceedingly small. No prior studies have identified any increased risk with utilizing either fibrin sealant or bupivacaine. This study will evaluate whether the intervention reduces bleeding risk.

  14 days

• Postoperative Pain; Study Terminated Due to FDA Requirement for a Investigational New Drug Application Requirement

  Parents/caregivers will be asked to perform thrice daily pain assessments utilizing a validated postoperative pain measurement scale for the 10 days after surgery. study terminated due to FDA requirement for a investigational new drug application requirement

  10 days

Secondary Outcomes (5)

• Total Pain Medication Usage

  10 days

• Time to Return to Normal Diet

  10 days

• Number of Required Calls to Healthcare Personnel (Either the Clinic or the Physician on Call Overnight)

  10 days

• Postoperative Nausea & Emesis

  10 days

• Time to Return to Normal Activity

  10 days

Study Arms (3)

Control

NO INTERVENTION

44 patients will be randomized to receive no topical treatment to their tonsillectomy (or adenotonsillectomy) wound bed as is the current standard of care at our institution. The wound bed will be treated with instrumentation in the operating room to ensure adequate hemostasis alone.

Fibrin Sealant Alone

ACTIVE COMPARATOR

44 patients will be randomized to receive application of topical fibrin sealant to their tonsillectomy (or adenotonsillectomy) wound bed to assess the pain reduction benefits of fibrin sealant alone. Prior to application of fibrin sealant, the wound bed will be treated with instrumentation in the operating room to ensure adequate hemostasis.

Biological: Fibrin Sealant

Bupivacaine-infused Fibrin Sealant

EXPERIMENTAL

44 patients will be randomized to receive application of topical bupivacaine-infused fibrin sealant to their tonsillectomy (or adenotonsillectomy) wound bed to assess the pain reduction benefits of fibrin sealant alone. Prior to application of fibrin sealant, the wound bed will be treated with instrumentation in the operating room to ensure adequate hemostasis.

Drug: Bupivacaine

Interventions

Bupivacaine DRUG

1 milliliter (mL) of 0.75% Bupivacaine Hydrochloride will be infused into 4mL of fibrin sealant (diluting the Bupivacaine HCl to 0.15%). The bupivacaine-infused fibrin sealant will then be applied to the tonsillectomy (or adenotonsillectomy) wound bed.

Also known as: Marcaine

Bupivacaine-infused Fibrin Sealant

Fibrin Sealant BIOLOGICAL

Fibrin sealant will be applied to the wound bed topically as per product instructions.

Also known as: Fibrin Glue

Fibrin Sealant Alone

Eligibility Criteria

• Age: 1 Year - 12 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• A) Chronic Pharyngitis / Recurrent Tonsillitis B) PAPFA (Periodic Aphthous Ulcers / Pharyngitis / Fevers / Adenopathy) Syndrome C) Upper Aerodigestive Obstruction Symptoms felt to be related to tonsil size. D) Adenotonsillar Hypertrophy (enlarged tonsils and adenoids) E) Obstructive Sleep Apnea (clinical diagnosis or by Polysomnogram \[sleep study\]) F) Chronic/Recurrent Tonsillolithiasis (tonsil stones)

You may not qualify if:

• Undergoing additional surgical procedures within 14 days preceding or following the tonsillectomy or adenotonsillectomy which could affect pain assessment scores.
• Additional concurrent surgical procedures (other than direct laryngoscopy, bronchoscopy, nasal endoscopy, ear examination under anesthesia, cerumen removal, or myringotomy with ear ventilation tube placement)
• \. If decision is made to perform supraglottoplasty for laryngomalacia intraoperatively
• \. Tonsillectomy or adenotonsillectomy for concern of malignancy of unknown primary
• \. Documented aprotinin allergy
• \. Documented amide anesthetic allergy
• \. Documented bleeding disorder
• \. Documented anticoagulant use
• \. Documented chronic pain disorder
• \. Documented chronic use of prescription narcotics or methadone
• \. Documented history of substance abuse or illicit drug use
• \. Documented history of alcoholism or alcohol abuse
• \. Gastrostomy/orogastric/nasogastric tube placement/use
• \. Planned postoperative ICU placement
• \. Refusal to participate

Sponsors & Collaborators

• Indiana University School of Medicine: lead

Study Sites (1)

Riley Childrens' Hospital

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Pain, Postoperative; Postoperative Hemorrhage; Pain; Hemorrhage

Interventions

Bupivacaine; Fibrin Tissue Adhesive

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Fibrin; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins

Limitations and Caveats

study closed due to need for FDA investigational new drug application.

Results Point of Contact

• Title: Bruce H. Matt, MD, MSc
• Organization: Indiana University

bmatt@iupui.edu

3172781215

Study Officials

• Bruce H Matt, MD,MSc

  Indiana University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 15, 2015
• First Posted: January 21, 2015
• Study Start: March 1, 2015
• Primary Completion: May 31, 2017
• Study Completion: May 31, 2017
• Last Updated: August 10, 2018
• Results First Posted: August 10, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)