Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis

Severe Sepsis Clinical Trial

— ACROSS  

Official title:

Phase IIa Randomized Controlled Trial of Acetaminophen for the Reduction of Oxidative Stress in Severe Sepsis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01739361
• Other study ID #: APAP-121486
• Status: Completed
• Phase: Phase 2
• First received: November 26, 2012
• Last updated: November 28, 2017
• Start date: April 2013
• Est. completion date: December 2013

Study information

• Verified date: November 2017
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Sepsis
• Severe Sepsis
• Toxemia

Intervention

Drug:
• Acetaminophen

• placebo

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	F2-isoprostanes After 72 Hours of Acetaminophen or Placebo	F2-isoprostanes are a marker of oxidative stress, specifically lipid peroxidation.	72 hours after randomization
Secondary	In-hospital Mortality	percent of patients who died in the hospital	Patients will be followed through the end of their hospital stay, an average of 5 weeks
Secondary	Serum Creatinine After 72 Hours of Treatment With Acetaminophen or Placebo	serum creatinine measurements at 72 hours	72 hours