Efficacy of Oral vs. Intravenous Acetaminophen

The Comparative Efficacy of Oral vs. Intravenous Acetaminophen in Sinus Surgery Patients

The comparative efficacy of intravenous (IV) to oral (PO-'per os') acetaminophen in the management of postoperative pain is understudied and largely unknown. In this observer blinded randomized clinical trial, investigators aim to determine the comparative efficacy of PO (preoperative) vs. IV (intraoperative) acetaminophen in a sinus surgery population.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: Oral Acetaminophen; Drug: Intravenous acetaminophen

Detailed Description

The comparative efficacy of intravenous (IV) to oral (PO-'per os') acetaminophen is understudied and largely unknown. Intravenous acetaminophen has been available since 2010 (http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022450lbl.pdf) and has proven superiority over placebo in human clinical trials. It is clearly advantageous in patients who cannot take oral medications. Similarly, oral acetaminophen has proven efficacy in the management of postoperative pain.

However, in patients who can receive either formulation the incremental cost of the IV formulation, both to the Health System and patient, is substantial. This incremental cost would be justifiable if there were clear efficacy or safety data to support the preferential use of IV over PO acetaminophen.

However, there is no evidence of superior safety and there are only two studies to our knowledge investigating the question of comparative efficacy. Fenlon et al. randomized 130 patients undergoing 3rd molar (i.e., wisdom tooth) removal to IV vs. PO acetaminophen and found that PO acetaminophen was non-inferior to IV acetaminophen. The primary endpoint was postoperative pain score 1h after surgery. No safety concerns were identified in either group. Pettersson et al. randomized cardiac surgery patients to IV or PO acetaminophen, starting immediately postoperatively through the following morning, and found a significant opioid sparing effect of IV acetaminophen but no difference in pain scores or nausea.

IV acetaminophen avoids first-pass hepatic metabolism and therefore generates higher serum and cerebrospinal fluid (CSF)/brain levels than does PO acetaminophen (http://ofirmev.com/Pharmacokinetics/). Based on the pharmacokinetic data, one can hypothesize that IV acetaminophen would be superior to PO acetaminophen at time points where serum and/or cerebrospinal fluid drug levels are higher.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • Zale Lipshy University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients aged 18 years or older
• Undergoing elective sinus surgery at Zale Lipshy Hospital

Exclusion Criteria:

• Inability of the patient to follow directions or comprehend either English or Spanish language.

  • Disorders of the liver which would make acetaminophen contraindicated (such as hepatitis, liver failure, prior liver transplant, etc).
  • Patients with chronic pain manifest by a baseline pain score > 4/10
  • Chronic opioid use (>2 weeks continuously), or illicit drug abuse
  • Body weight < 50 kg.
  • Patients with contraindications to any of the study drugs (such as Malignant Hyperthermia susceptible, celecoxib or sulfa allergy, etc.).
  • Patients who have taken analgesic medications on the morning of surgery (prior to arrival).
  • Allergy to acetaminophen

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral Acetaminophen; Oral Acetaminophen 1-hour before surgery	Drug: Oral Acetaminophen; 1000mg oral acetaminophen + 400mg oral celecoxib given within one hour of incision; Other Names: Tylenol
Active Comparator: Intravenous Acetaminophen; Intravenous Acetaminophen within 1-hour prior to anesthetic emergence	Drug: Intravenous acetaminophen; 400mg oral celecoxib given within one hour of incision + 1000mg IV acetaminophen within one hour prior to anesthetic emergence.; Other Names: Tylenol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Pain Score on the Scale of 10 (0=No Pain and 10=Worst Pain)	Pain score on the scale of 10 at 1-h postoperatively in the Post-Anesthesia Care Unit (PACU)	1-h postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Morphine Equivalents of Postoperative Opioid Usage	Total amount of postoperative opioid usage at Postoperative Anesthesia Care Unit (PACU), an expected average of 6 hours	an expected average of 6 hours

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: David McDonagh, MD, UT Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2015
• Primary Completion (Actual): September 2, 2016
• Study Completion (Actual): January 15, 2018

Study Registration Dates

• First Submitted: June 2, 2015
• First Submitted That Met QC Criteria: December 29, 2015
• First Posted (Estimate): December 31, 2015

Study Record Updates

• Last Update Posted (Actual): April 21, 2020
• Last Update Submitted That Met QC Criteria: April 20, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Postoperative pain; Acetaminophen; Sinus Surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: 052015-068

Plan for Individual participant data (IPD)

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