Clinical trial NCT02643394: Efficacy of Oral vs. Intravenous Acetaminophen
Official title: The Comparative Efficacy of Oral vs. Intravenous Acetaminophen in Sinus Surgery Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Postoperative Pain
Keywords: Acetaminophen
Postoperative pain
Sinus Surgery
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2015-12-31
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Postoperative Pain Score on the Scale of 10 (0=No Pain and 10=Worst Pain)
timeFrame: 1-h postoperatively
Secondary outcomes:
measure: Morphine Equivalents of Postoperative Opioid Usage
timeFrame: an expected average of 6 hours
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Zale Lipshy University Hospital
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: David McDonagh, MD
role: PRINCIPAL_INVESTIGATOR
References: