Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis (ACROSS)
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Phase IIa Randomized Controlled Trial of Acetaminophen for the Reduction of Oxidative Stress in Severe Sepsis|
- F2-isoprostanes after 72 hours of Acetaminophen or Placebo, adjusted for baseline F2-Isoprostane level [ Time Frame: 72 hours after randomization ] [ Designated as safety issue: No ]F2-isoprostanes are a marker of oxidative stress, specifically lipid peroxidation.
- In-hospital Mortality [ Time Frame: Patients will be followed through the end of their hospital stay, an average of 5 weeks ] [ Designated as safety issue: No ]
- Serum Creatinine after 72 hours of treatment with Acetaminophen or Placebo, adjusted for baseline Creatinine [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
|Study Start Date:||April 2013|
|Estimated Study Completion Date:||March 2014|
|Estimated Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
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 Comparator: Placebo
Patients will receive placebo by mouth or by enteral feeding tube every six hours for 72 hours.
|Contact: David R Janz, M.D.||email@example.com|
|United States, Tennessee|
|Vanderbilt University Medical Center||Recruiting|
|Nashville, Tennessee, United States, 37232|
|Contact: David R Janz, M.D. 615-835-1710 firstname.lastname@example.org|
|Principal Investigator: David R Janz, M.D.|
|Principal Investigator: Lorraine B Ware, M.D.|