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

Primary Purpose

Severe Sepsis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Acetaminophen
placebo
Sponsored by
Vanderbilt University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Severe Sepsis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Acetaminophen

Placebo

Arm Description

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.

Patients will receive placebo by mouth or by enteral feeding tube every six hours for 72 hours.

Outcomes

Primary Outcome Measures

F2-isoprostanes After 72 Hours of Acetaminophen or Placebo
F2-isoprostanes are a marker of oxidative stress, specifically lipid peroxidation.

Secondary Outcome Measures

In-hospital Mortality
percent of patients who died in the hospital
Serum Creatinine After 72 Hours of Treatment With Acetaminophen or Placebo
serum creatinine measurements at 72 hours

Full Information

First Posted
November 26, 2012
Last Updated
November 28, 2017
Sponsor
Vanderbilt University
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1. Study Identification

Unique Protocol Identification Number
NCT01739361
Brief Title
Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis
Acronym
ACROSS
Official Title
Phase IIa Randomized Controlled Trial of Acetaminophen for the Reduction of Oxidative Stress in Severe Sepsis
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
April 2013 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Sepsis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Acetaminophen
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients will receive placebo by mouth or by enteral feeding tube every six hours for 72 hours.
Intervention Type
Drug
Intervention Name(s)
Acetaminophen
Intervention Type
Drug
Intervention Name(s)
placebo
Primary Outcome Measure Information:
Title
F2-isoprostanes After 72 Hours of Acetaminophen or Placebo
Description
F2-isoprostanes are a marker of oxidative stress, specifically lipid peroxidation.
Time Frame
72 hours after randomization
Secondary Outcome Measure Information:
Title
In-hospital Mortality
Description
percent of patients who died in the hospital
Time Frame
Patients will be followed through the end of their hospital stay, an average of 5 weeks
Title
Serum Creatinine After 72 Hours of Treatment With Acetaminophen or Placebo
Description
serum creatinine measurements at 72 hours
Time Frame
72 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States

12. IPD Sharing Statement

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Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis

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