Modified Pre-operative Oral Doses Acetaminophen Versus Intravenous Acetaminophen (MODIV-APAP)

Acetaminophen is frequently used as an adjunct for pain management in pediatric surgical patients. The drug is available in an over the counter, inexpensive oral form as well as a considerably more expensive intravenous form. This study will compare opioid requirements and acetaminophen plasma levels post operatively for two dosing regimens to compare oral versus intravenous routes given pre operatively.

Study Overview

• Status: Completed
• Conditions: Tonsillectomy; Adenoidectomy
• Intervention / Treatment: Drug: Acetaminophen

Detailed Description

The primary purpose of this study is to compare opioid utilization in post-operative patients undergoing tonsillectomy and adenoidectomy, between IV and PO acetaminophen. Secondarily, it will provide information regarding possible cost savings, pharmacokinetics and safety between these two regimens.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California Davis Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients ages 3 years to 17 years scheduled for tonsillectomy and adenoidectomy for obstructive sleep apnea with or without additional minor procedures such as sleep endoscopy, unilateral or bilateral myringotomy, insertion of tympanostomy tubes and/or ear exam. ( Minor additional procedures that are frequently combined with tonsillectomy and adenoidectomy but are not commonly considered to have pain that is significantly greater than the tonsillectomy and adenoidectomy).

Exclusion Criteria:

• Patients who meet University of California Davis Children's Hospital (UCDCH) criteria for Pediatric Intensive Care Unit (PICU) admission: on home oxygen pre-operatively, exhibit airway obstruction when awake (stertor above larynx, stridor at larynx), sleep study with apnea hypoxia index greater than 25 or sleep oxygen saturation nadir <80%, cardiac disease, difficult intubation.
• Patients with a known allergy to acetaminophen
• Patients with known hepatic insufficiency or severe hepatic disease
• Patients with known Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• Patients who are malnourished (ie lower levels of glutathione)
• Patients with severe renal impairment as defined by calculated creatinine clearance <20 ml/min (per modified Schwarz equation)
• Patients who are pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Oral Acetaminophen; Group 1 will receive oral acetaminophen 30mg/kg 30-60 minutes prior to scheduled surgery time . Group 1 patients will receive placebo IV infusion just prior to surgery incision.	Drug: Acetaminophen; already included in arm/group descriptions; Other Names: OFIRMEV
EXPERIMENTAL: Intravenous Acetaminophen; Group 2 will receive placebo oral medication at approximately 30-60 minutes prior to scheduled surgery. Group 2 patients will receive IV acetaminophen 15 mg/kg just prior to surgery incision.	Drug: Acetaminophen; already included in arm/group descriptions; Other Names: OFIRMEV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Dose of Opioid	Total dose of opioid, in morphine equivalents, that the patient receives for breakthrough pain in the 24 hour period following surgery.	Within 24hrs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients With Severe Pain Score of 7 or Higher	A secondary endpoint is the proportion of patients with pain scores in the severe pain range (7 or higher) on numeric pain rating scale of 0 to 10; higher score more severe.	24 hrs period following surgery
Plasma Acetaminophen Level 1 - End of Surgery	mg/L acetaminophen in the plasma at the end of surgery	at the end of surgery, about 1 hour after IV Dose
Plasma Acetaminophen Level 2 - 3 Hours After IV Study Drug Administration	mg/L acetaminophen in the plasma 3 hours after IV study drug administration	Outcome will be measured 3hrs post first IV Dose

Collaborators and Investigators

• Sponsor: University of California, Davis
• Investigators: Principal Investigator: Cathy Lammers, MD, UC Davis Children's Hospital

Publications and helpful links

General Publications

• Lammers CR, Schwinghammer AJ, Hall B, Kriss RS, Aizenberg DA, Funamura JL, Senders CW, Nittur V, Applegate RL 2nd. Comparison of Oral Loading Dose to Intravenous Acetaminophen in Children for Analgesia After Tonsillectomy and Adenoidectomy: A Randomized Clinical Trial. Anesth Analg. 2021 Dec 1;133(6):1568-1576. doi: 10.1213/ANE.0000000000005678.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 28, 2017
• Primary Completion (ACTUAL): July 3, 2019
• Study Completion (ACTUAL): July 3, 2019

Study Registration Dates

• First Submitted: December 13, 2016
• First Submitted That Met QC Criteria: December 15, 2016
• First Posted (ESTIMATE): December 16, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 18, 2021
• Last Update Submitted That Met QC Criteria: January 28, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: 948256

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