Efficacy of Oral vs. Intravenous Acetaminophen

• ClinicalTrials.gov Identifier: NCT02643394
• Recruitment Status: Completed
• First Posted: December 31, 2015
• Results First Posted: May 7, 2018
• Last Update Posted: July 3, 2018
• Sponsor: University of Texas Southwestern Medical Center
• Information provided by (Responsible Party): University of Texas Southwestern Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Postoperative Pain	Drug: Oral Acetaminophen; Drug: Intravenous acetaminophen	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 110 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Comparative Efficacy of Oral vs. Intravenous Acetaminophen in Sinus Surgery Patients
• Actual Study Start Date: August 17, 2015
• Actual Primary Completion Date: September 2, 2016
• Actual Study Completion Date: January 15, 2018

Arms and Interventions

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 Name: 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 Name: Tylenol

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Morphine Equivalents of Postoperative Opioid Usage [ Time Frame: an expected average of 6 hours ]
   Total amount of postoperative opioid usage at Postoperative Anesthesia Care Unit (PACU), an expected average of 6 hours

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Texas

Zale Lipshy University Hospital

Dallas, Texas, United States, 75390

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Investigators

• Principal Investigator: David McDonagh, MD; UT Southwestern Medical Center

More Information

• Responsible Party: University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT02643394 History of Changes
• Other Study ID Numbers: 052015-068
• First Posted: December 31, 2015
• Results First Posted: May 7, 2018
• Last Update Posted: July 3, 2018
• Last Verified: June 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by University of Texas Southwestern Medical Center:

Acetaminophen; Postoperative pain; Sinus Surgery

Additional relevant MeSH terms:

Acetaminophen; Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pain; Neurologic Manifestations; Signs and Symptoms; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Antipyretics