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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
David Janz, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01739361
First received: November 26, 2012
Last updated: December 21, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Severe Sepsis
Drug: Acetaminophen
Drug: placebo
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 51
Study Start Date: April 2013
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01739361

Locations
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
  More Information

No publications provided

Responsible Party: David Janz, Principal Investigator, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01739361     History of Changes
Other Study ID Numbers: APAP-121486
Study First Received: November 26, 2012
Last Updated: December 21, 2013
Health Authority: United States: Data and Safety Monitoring Board
United States: Institutional Review Board

Additional relevant MeSH terms:
Sepsis
Toxemia
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Acetaminophen
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Antipyretics

ClinicalTrials.gov processed this record on September 18, 2014