Postoperative Ibuprofen Use and Risk of Bleeding in Pediatric Tonsillectomy

NCT03385057 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 17-167H
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 5

Brief Summary

Pediatric tonsillectomy is one of the most common surgical procedures annually in the United States; risks include postoperative hemorrhage and poor pain control. Controversy exists regarding optimal pharmacologic pain management following surgery, as each drug's efficacy is balanced by its specific side effects. Ibuprofen is effective in controlling postoperative pain following tonsillectomy, but its mechanism of action results in decreased platelet function, which may increase postoperative bleeding events. This is a multicenter, randomized control non-inferiority trial designed to assess the relationship between short-course ibuprofen use and post-tonsillectomy bleeding when compared to acetaminophen.

Conditions

Tonsillectomy With or Without Adenoidectomy

Outcome Measures

Primary Outcomes (1)

• Post-tonsillectomy bleeding within 14 days of surgery.

  This will be classified by timing (\<24 hours vs. 24 hours or more) and severity (level 1: bleeding by history alone; level 2: objective bleeding requiring hospital admission and observation; level 3: objective bleeding requiring operative intervention). Bleeding events will be documented during postoperative visit at two weeks as well as through medical record review.

  Within 14 days of surgery

Secondary Outcomes (1)

• Post-tonsillectomy pain control data through 14 days of surgery

  Through 14 days of surgery

Study Arms (2)

Ibuprofen Arm

ACTIVE COMPARATOR

Drug: Ibuprofen

Acetaminophen

ACTIVE COMPARATOR

Drug: Acetaminophen

Interventions

Ibuprofen DRUG

Grape-flavored ibuprofen 100mg/5mL (Leader®) will be dispensed. Ibuprofen will be dosed at 10mg/kg (max dose 600mg) QID (roughly Q6 hours, however we left dosing QID to allow for some flexibility in the dosing schedule to accommodate patient sleeping schedules). The pharmacy will manipulate the volume of each medication using Ora Blend suspension so that for each child, weight-based dosing of each medication will be equivalent in volume. The first dose of study medication will be dispensed 4 hours after the preoperative acetaminophen dose. Thereafter, medication will be dosed QID (or roughly 6 hours apart). Surgeons, nursing staff, and patients and their families will be blinded regarding the type of medication administered.

Also known as: Motrin

Ibuprofen Arm

Acetaminophen DRUG

Grape-flavored acetaminophen 160mg/5mL (Leader®) will be dispensed based upon the arm to which each participant has been randomized. Acetaminophen at 15mg/kg (max dose 650mg), dosing will be QID (roughly Q6 hours, however we left dosing QID to allow for some flexibility in the dosing schedule to accommodate patient sleeping schedules). The pharmacy will manipulate the volume of each medication using Ora Blend suspension so that for each child, weight-based dosing of each medication will be equivalent in volume. The first dose of study medication will be dispensed 4 hours after the preoperative acetaminophen dose. Thereafter, medication will be dosed QID (or roughly 6 hours apart). Surgeons, nursing staff, and patients and their families will be blinded regarding the type of medication administered.

Also known as: Advil

Acetaminophen

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male and female patients ages 2-18 undergoing tonsillectomy with or without adenoidectomy by electrocautery alone for all indications
• Patients with complex medical conditions and craniofacial abnormalities will be included.
• Family must understand and be able to read English.
• Only patients who are not pregnant will be included.
• Informed consent and, child assent (when appropriate) will be required for enrollment. Patients will provide signed and dated informed consent form.
• Subjects will be willing and able to comply with all study procedures and be available for the duration of the study.

You may not qualify if:

• Patients with a known personal or family history of a bleeding disorder.
• Patients with a history of asthma, kidney or liver problems.
• Patients with tonsillectomy or adenoidectomy performed using a cold knife technique, microdebrider, coblation or plasma knife.
• Patients on NSAIDs for other medical conditions or those who have taken NSAIDs within 1 week of surgery
• Patients with allergy to aspirin or other NSAIDs, acetaminophen, Red Dye #40 or Red Dye #33
• Patients found to be pregnant will be excluded from participation. Pregnancy testing using urine beta-HCG will be performed on all children \> 13 years of age, or those younger than 13 who are menstruating; this is the testing protocol used at the Children's Hospital of Boston.
• Patients unwilling to enroll in the study will have the tonsillectomy with or without adenoidectomy performed according to current practice standards.

Sponsors & Collaborators

• Massachusetts Eye and Ear Infirmary: lead
• Emory University: collaborator
• University Hospitals Cleveland Medical Center: collaborator
• Madigan Army Medical Center: collaborator
• United States Naval Medical Center, Portsmouth: collaborator
• Rady Children's Hospital, San Diego: collaborator

Study Sites (5)

Rady's Children's Hospital

San Diego, California, 92123, United States

Location

Emory University and Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Case Western University- Raimbow Babies and Children's

Cleveland, Ohio, 44106, United States

Location

Portsmouth Naval Hospital

Portsmouth, Virginia, 23708-2197, United States

Location

Madigan Army Hospital

Tacoma, Washington, 98431, United States

Location

Related Publications (23)

• Baugh RF, Archer SM, Mitchell RB, Rosenfeld RM, Amin R, Burns JJ, Darrow DH, Giordano T, Litman RS, Li KK, Mannix ME, Schwartz RH, Setzen G, Wald ER, Wall E, Sandberg G, Patel MM; American Academy of Otolaryngology-Head and Neck Surgery Foundation. Clinical practice guideline: tonsillectomy in children. Otolaryngol Head Neck Surg. 2011 Jan;144(1 Suppl):S1-30. doi: 10.1177/0194599810389949.

  PMID: 21493257 BACKGROUND

• Boss EF, Marsteller JA, Simon AE. Outpatient tonsillectomy in children: demographic and geographic variation in the United States, 2006. J Pediatr. 2012 May;160(5):814-9. doi: 10.1016/j.jpeds.2011.11.041. Epub 2011 Dec 17.

  PMID: 22183449 BACKGROUND

• Alexander NS, Schroeder JW Jr. Pediatric obstructive sleep apnea syndrome. Pediatr Clin North Am. 2013 Aug;60(4):827-40. doi: 10.1016/j.pcl.2013.04.009.

  PMID: 23905822 BACKGROUND

• Schwengel DA, Dalesio NM, Stierer TL. Pediatric obstructive sleep apnea. Anesthesiol Clin. 2014 Mar;32(1):237-61. doi: 10.1016/j.anclin.2013.10.012.

  PMID: 24491659 BACKGROUND

• Spicuzza L, Leonardi S, La Rosa M. Pediatric sleep apnea: early onset of the 'syndrome'? Sleep Med Rev. 2009 Apr;13(2):111-22. doi: 10.1016/j.smrv.2008.07.001. Epub 2008 Dec 5.

  PMID: 19058983 BACKGROUND

• Randall DA, Hoffer ME. Complications of tonsillectomy and adenoidectomy. Otolaryngol Head Neck Surg. 1998 Jan;118(1):61-8. doi: 10.1016/S0194-5998(98)70376-6.

  PMID: 9450830 BACKGROUND

• Subramanyam R, Varughese A, Willging JP, Sadhasivam S. Future of pediatric tonsillectomy and perioperative outcomes. Int J Pediatr Otorhinolaryngol. 2013 Feb;77(2):194-9. doi: 10.1016/j.ijporl.2012.10.016. Epub 2012 Nov 16.

  PMID: 23159321 BACKGROUND

• Tan GX, Tunkel DE. Control of Pain After Tonsillectomy in Children: A Review. JAMA Otolaryngol Head Neck Surg. 2017 Sep 1;143(9):937-942. doi: 10.1001/jamaoto.2017.0845.

  PMID: 28662233 BACKGROUND

• Cohen N, Sommer DD. Post-tonsillectomy pain control: consensus or controversy? Pain Manag. 2016;6(1):31-7. doi: 10.2217/pmt.15.58. Epub 2015 Dec 17.

  PMID: 26678541 BACKGROUND

• Moir MS, Bair E, Shinnick P, Messner A. Acetaminophen versus acetaminophen with codeine after pediatric tonsillectomy. Laryngoscope. 2000 Nov;110(11):1824-7. doi: 10.1097/00005537-200011000-00011.

  PMID: 11081593 BACKGROUND

• Isaacson G. Pediatric tonsillectomy: an evidence-based approach. Otolaryngol Clin North Am. 2014 Oct;47(5):673-90. doi: 10.1016/j.otc.2014.06.011. Epub 2014 Aug 7.

  PMID: 25213277 BACKGROUND

• Isaacson G. Tonsillectomy care for the pediatrician. Pediatrics. 2012 Aug;130(2):324-34. doi: 10.1542/peds.2011-3857. Epub 2012 Jul 2.

  PMID: 22753552 BACKGROUND

• Romsing J, Hertel S, Harder A, Rasmussen M. Examination of acetaminophen for outpatient management of postoperative pain in children. Paediatr Anaesth. 1998;8(3):235-9. doi: 10.1046/j.1460-9592.1998.00768.x.

  PMID: 9608969 BACKGROUND

• Zubieta JK, Smith YR, Bueller JA, Xu Y, Kilbourn MR, Jewett DM, Meyer CR, Koeppe RA, Stohler CS. Regional mu opioid receptor regulation of sensory and affective dimensions of pain. Science. 2001 Jul 13;293(5528):311-5. doi: 10.1126/science.1060952.

  PMID: 11452128 BACKGROUND

• Sadhasivam S, Myer CM 3rd. Preventing opioid-related deaths in children undergoing surgery. Pain Med. 2012 Jul;13(7):982-3; author reply 984. doi: 10.1111/j.1526-4637.2012.01419.x. Epub 2012 Jun 13.

  PMID: 22694279 BACKGROUND

• Whittaker MR. Opioid use and the risk of respiratory depression and death in the pediatric population. J Pediatr Pharmacol Ther. 2013 Oct;18(4):269-76. doi: 10.5863/1551-6776-18.4.269.

  PMID: 24719587 BACKGROUND

• Burian M, Geisslinger G. COX-dependent mechanisms involved in the antinociceptive action of NSAIDs at central and peripheral sites. Pharmacol Ther. 2005 Aug;107(2):139-54. doi: 10.1016/j.pharmthera.2005.02.004. Epub 2005 Apr 19.

  PMID: 15993252 BACKGROUND

• Goldenberg NA, Jacobson L, Manco-Johnson MJ. Brief communication: duration of platelet dysfunction after a 7-day course of Ibuprofen. Ann Intern Med. 2005 Apr 5;142(7):506-9. doi: 10.7326/0003-4819-142-7-200504050-00009.

  PMID: 15809462 BACKGROUND

• Rainsford KD. Ibuprofen: pharmacology, efficacy and safety. Inflammopharmacology. 2009 Dec;17(6):275-342. doi: 10.1007/s10787-009-0016-x. Epub 2009 Nov 21.

  PMID: 19949916 BACKGROUND

• St Charles CS, Matt BH, Hamilton MM, Katz BP. A comparison of ibuprofen versus acetaminophen with codeine in the young tonsillectomy patient. Otolaryngol Head Neck Surg. 1997 Jul;117(1):76-82. doi: 10.1016/S0194-59989770211-0.

  PMID: 9230328 BACKGROUND

• Kelly LE, Sommer DD, Ramakrishna J, Hoffbauer S, Arbab-Tafti S, Reid D, Maclean J, Koren G. Morphine or Ibuprofen for post-tonsillectomy analgesia: a randomized trial. Pediatrics. 2015 Feb;135(2):307-13. doi: 10.1542/peds.2014-1906.

  PMID: 25624387 BACKGROUND

• Harley EH, Dattolo RA. Ibuprofen for tonsillectomy pain in children: efficacy and complications. Otolaryngol Head Neck Surg. 1998 Nov;119(5):492-6. doi: 10.1016/S0194-5998(98)70107-X.

  PMID: 9807075 BACKGROUND

• Lewis SR, Nicholson A, Cardwell ME, Siviter G, Smith AF. Nonsteroidal anti-inflammatory drugs and perioperative bleeding in paediatric tonsillectomy. Cochrane Database Syst Rev. 2013 Jul 18;2013(7):CD003591. doi: 10.1002/14651858.CD003591.pub3.

  PMID: 23881651 BACKGROUND

MeSH Terms

Interventions

Ibuprofen; Acetaminophen

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Acetanilides; Anilides; Amides; Aniline Compounds; Amines

Study Officials

• Christopher J Hartnick, MD

  Massachusetts Eye and Ear

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2017
• First Posted: December 28, 2017
• Study Start: September 1, 2018
• Primary Completion: January 1, 2023
• Study Completion: January 1, 2023
• Last Updated: September 20, 2018

Record last verified: 2018-09

Locations

US (5)