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

Vanderbilt University

Status and phase: Completed; Phase 2

Conditions: Severe Sepsis

Treatments: Drug: placebo; Drug: Acetaminophen

Study type: Interventional

Funder types: Other

Identifiers

NCT01739361

APAP-121486

Details and patient eligibility

About

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.

Enrollment: 44 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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44 participants in 2 patient groups, including a placebo group

Acetaminophen

Experimental group

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.

Treatment:

Drug: Acetaminophen

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: placebo