COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis (ACROSS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01739361
Recruitment Status : Completed
First Posted : December 3, 2012
Results First Posted : March 23, 2015
Last Update Posted : December 26, 2017
Information provided by (Responsible Party):
David Janz, 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.

Condition or disease Intervention/treatment Phase
Severe Sepsis Drug: Acetaminophen Drug: placebo Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase IIa Randomized Controlled Trial of Acetaminophen for the Reduction of Oxidative Stress in Severe Sepsis
Study Start Date : April 2013
Actual Primary Completion Date : December 2013
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis

Arm Intervention/treatment
Experimental: 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.
Drug: Acetaminophen
Placebo Comparator: Placebo
Patients will receive placebo by mouth or by enteral feeding tube every six hours for 72 hours.
Drug: placebo

Primary Outcome Measures :
  1. F2-isoprostanes After 72 Hours of Acetaminophen or Placebo [ Time Frame: 72 hours after randomization ]
    F2-isoprostanes are a marker of oxidative stress, specifically lipid peroxidation.

Secondary Outcome Measures :
  1. In-hospital Mortality [ Time Frame: Patients will be followed through the end of their hospital stay, an average of 5 weeks ]
    percent of patients who died in the hospital

  2. Serum Creatinine After 72 Hours of Treatment With Acetaminophen or Placebo [ Time Frame: 72 hours ]
    serum creatinine measurements at 72 hours

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01739361

Layout table for location information
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University

Layout table for additonal information
Responsible Party: David Janz, Principal Investigator, Vanderbilt University Identifier: NCT01739361    
Other Study ID Numbers: APAP-121486
First Posted: December 3, 2012    Key Record Dates
Results First Posted: March 23, 2015
Last Update Posted: December 26, 2017
Last Verified: November 2017
Additional relevant MeSH terms:
Layout table for MeSH terms
Systemic Inflammatory Response Syndrome
Pathologic Processes
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs