Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis

Phase 2

Completed

• Conditions: Severe Sepsis
• Interventions: Drug: Acetaminophen; Drug: placebo

• Registration Number: NCT01739361
• Lead Sponsor: Vanderbilt University

Brief Summary

Cell-free hemoglobin can be measured in the plasma of patients with sickle cell anemia, hemodialysis, after red blood cell transfusion, and in patients with sepsis. Cell-free hemoglobin in these patient population has been associated with poor outcomes, including an association with an increased risk of death. Acetaminophen may have a protective effect in these patient populations by inhibiting hemoprotein-mediated lipid peroxidation. The purpose of the present trial is to study the effect of acetaminophen on lipid peroxidation in adults with severe sepsis and detectable cell-free hemoglobin.

The primary hypothesis is that systemic markers of oxidative stress and lipid peroxidation, as measured by F2-isoprostanes, will be significantly lower in patients with severe sepsis and detectable cell-free hemoglobin who receive acetaminophen compared to placebo. The secondary hypothesis is that patients with severe sepsis and detectable cell-free hemoglobin treated with acetaminophen will have better clinical outcomes, including decreased incidence of acute kidney injury and lower rates of hospital mortality, compared to those who receive placebo.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-11-26
• Study First Submitted QC: 2012-11-30
• Study First Posted: 2012-12-03
• Study Start: 2013-04
• Primary Completion: 2013-12
• Study Completion: 2013-12
• Results First Submitted: 2015-03-11
• Results First Submitted QC: 2015-03-19
• Results First Posted: 2015-03-23
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-28
• Last Update Posted: 2017-12-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

• Males and Female >=18 years old
• Admitted to an Intensive Care Unit
• Severe Sepsis
• Detectable plasma cell-free hemoglobin

Exclusion Criteria

• patients who received acetaminophen in the past 48 hours prior to enrollment
• intolerance or allergy to acetaminophen
• measured AST/ALT >400 U/L in the 24 hours prior to enrollment
• chronic liver disease defined by a Child-Pugh score >4
• cannot swallow or have no enteral feeding access
• patients with no detectable cell-free hemoglobin
• patients transitioned to palliative care
• pregnant patients or women of childbearing potential without a documented pregnancy test

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Acetaminophen	Acetaminophen	Patients will receive acetaminophen at the dose of 1 gram by mouth or by enteral feeding tube every six hours for a total of 72 hours.
Placebo	placebo	Patients will receive placebo by mouth or by enteral feeding tube every six hours for 72 hours.

Primary Outcome Measures

Name	Time	Method
F2-isoprostanes After 72 Hours of Acetaminophen or Placebo	72 hours after randomization	F2-isoprostanes are a marker of oxidative stress, specifically lipid peroxidation.

Secondary Outcome Measures

Name	Time	Method
Serum Creatinine After 72 Hours of Treatment With Acetaminophen or Placebo	72 hours	serum creatinine measurements at 72 hours
In-hospital Mortality	Patients will be followed through the end of their hospital stay, an average of 5 weeks	percent of patients who died in the hospital

Trial Locations

Locations (1)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States