Efficacy of Acetaminophen in Posterior Fossa Surgery

NCT02532322 | Withdrawn Phase 2 DMC

• 1 other identifier: PRO00006330
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Uncontrolled pain after posterior fossa surgery and associated negative side effects of conventional opioid therapy causes significant morbidity and mortality in infants and children. Intravenous (IV) acetaminophen has been shown to be effective in treating mild to moderate pain, and moderate to severe pain in conjunction with adjuvant opioids in children. However, it is unknown if IV acetaminophen is effective as analgesic adjuvant therapy in children undergoing posterior fossa surgery. In this prospective, randomized controlled trial, the investigators aim to determine whether the addition of IV acetaminophen for 24 hours can lead to reduction in postoperative pain and opioid requirement after neurosurgical procedures of the posterior fossa compared with conventional therapy.

Conditions

Arnold-Chiari Malformation; Posterior Fossa Tumors

Outcome Measures

Primary Outcomes (1)

• Daily opioid consumption (mg/kg/24 hours using morphine equivalent)

  Equianalgesic conversion of opioid consumption to morphine equivalent will be used

  72 hours postoperatively

Secondary Outcomes (3)

• Average daily pain scores using Wong-Baker Faces or Numeric Pain Scale

  72 hours postoperatively

• Average daily sedation scores using University of Michigan Sedation Scale

  72 hours postoperatively

• Incidence of opioid-induced side effects

  72 hours postoperatively

Study Arms (2)

IV acetaminophen

EXPERIMENTAL

IV acetaminophen 15 mg/kg (1.5 mL/kg) IV loading dose prior to incision, followed by a 15 mg/kg (1.5 mL/kg) dose given every 6 hours for the first 24 hours after surgery (total of 4 doses postoperatively)

Drug: IV acetaminophen

normal saline

PLACEBO COMPARATOR

normal saline (placebo control) 1.5 mL/kg IV loading dose prior to incision, followed by a 1.5 mL/kg dose given every 6 hours for the first 24 hours after surgery (total of 4 doses postoperatively)

Drug: normal saline

Interventions

IV acetaminophen DRUG

IV acetaminophen 15 mg/kg (1.5 mL/kg) IV loading dose prior to incision, followed by a 15 mg/kg (1.5 mL/kg) dose given every 6 hours for the first 24 hours after surgery (total of 4 doses postoperatively)

Also known as: Tylenol, APAP

IV acetaminophen

normal saline DRUG

normal saline 1.5 mL/kg IV loading dose prior to incision, followed by a 1.5 mL/kg dose given every 6 hours for the first 24 hours after surgery (total of 4 doses postoperatively)

Also known as: saline placebo, NS 0.9%

normal saline

Eligibility Criteria

• Age: 2 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Any child undergoing posterior fossa surgery, including surgery for Chiari Malformation
• The subject's American Society of Anesthesiologists physical status is 1, 2 or 3
• Males and females 2 to 12 years old (minorities will be included) - recommended dosing of IV acetaminophen in children is approved for children 2 to 12 years of age
• Written informed consent from parent/guardian

You may not qualify if:

• Subjects with known or suspected hypersensitivity reaction to acetaminophen
• Presence or prior history of a known liver disease or coagulation disorder:
• History of abnormal liver function
• History of prior liver transplantation
• Subjects who are on anticoagulant therapy (Coumadin, heparin, aspirin, etc.)
• History of prior acetaminophen overdose
• Subjects with the need for mechanical ventilation prior to surgery or postoperatively - unable to assess accurate pain scores in this context
• The subject has a history or a family (parent or sibling) history of malignant hyperthermia
• The subject had a recent opioid exposure (within 1 month of surgery)
• The subject is obese (body mass index \>30 kg/m2)
• The subject is an American Society of Anesthesiologist physical status classification of 4 or greater
• The subject is scheduled for a surgical sub-procedure
• Subjects who have been previously enrolled in this protocol may not be enrolled again

Sponsors & Collaborators

• Children's National Research Institute: lead

Study Sites (1)

Children's National Health System

Washington D.C., District of Columbia, 20010, United States

Location

Related Publications (6)

• De Benedittis G, Lorenzetti A, Migliore M, Spagnoli D, Tiberio F, Villani RM. Postoperative pain in neurosurgery: a pilot study in brain surgery. Neurosurgery. 1996 Mar;38(3):466-9; discussion 469-70. doi: 10.1097/00006123-199603000-00008.

  PMID: 8837797 BACKGROUND

• Morad A, Winters B, Stevens R, White E, Weingart J, Yaster M, Gottschalk A. The efficacy of intravenous patient-controlled analgesia after intracranial surgery of the posterior fossa: a prospective, randomized controlled trial. Anesth Analg. 2012 Feb;114(2):416-23. doi: 10.1213/ANE.0b013e31823f0c5a. Epub 2011 Dec 9.

  PMID: 22156333 BACKGROUND

• Baley K, Michalov K, Kossick MA, McDowell M. Intravenous acetaminophen and intravenous ketorolac for management of pediatric surgical pain: a literature review. AANA J. 2014 Feb;82(1):53-64.

  PMID: 24654353 BACKGROUND

• Alhashemi JA, Daghistani MF. Effect of intraoperative intravenous acetaminophen vs. intramuscular meperidine on pain and discharge time after paediatric dental restoration. Eur J Anaesthesiol. 2007 Feb;24(2):128-33. doi: 10.1017/S0265021506001232. Epub 2006 Aug 8.

  PMID: 16895621 BACKGROUND

• Alhashemi JA, Daghistani MF. Effects of intraoperative i.v. acetaminophen vs i.m. meperidine on post-tonsillectomy pain in children. Br J Anaesth. 2006 Jun;96(6):790-5. doi: 10.1093/bja/ael084. Epub 2006 Apr 13.

  PMID: 16613928 BACKGROUND

• Lahtinen P, Kokki H, Hendolin H, Hakala T, Hynynen M. Propacetamol as adjunctive treatment for postoperative pain after cardiac surgery. Anesth Analg. 2002 Oct;95(4):813-9, table of contents. doi: 10.1097/00000539-200210000-00005.

  PMID: 12351250 BACKGROUND

MeSH Terms

Conditions

Arnold-Chiari Malformation; Infratentorial Neoplasms

Interventions

Acetaminophen; Saline Solution

Condition Hierarchy (Ancestors)

Neural Tube Defects; Nervous System Malformations; Nervous System Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Srijaya K Reddy, MD, MBA

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 21, 2015
• First Posted: August 25, 2015
• Study Start: November 1, 2015
• Primary Completion: June 1, 2018
• Study Completion: October 1, 2018
• Last Updated: April 8, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)