Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis

Vanderbilt University44 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Severe Sepsis

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

F2-isoprostanes After 72 Hours of Acetaminophen or Placebo

F2-isoprostanes are a marker of oxidative stress, specifically lipid peroxidation.

Time frame: 72 hours after randomization

Secondary Outcomes

In-hospital Mortality

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

Serum Creatinine After 72 Hours of Treatment With Acetaminophen or Placebo

serum creatinine measurements at 72 hours

Time frame: 72 hours