Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis

Study Overview
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Brief Summary
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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.

Official Title
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Phase IIa Randomized Controlled Trial of Acetaminophen for the Reduction of Oxidative Stress in Severe Sepsis

Conditions
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Severe Sepsis

Intervention / Treatment
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* Drug: Acetaminophen
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetaminophen<br>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<br> <br> |
| Placebo Comparator: Placebo<br>Patients will receive placebo by mouth or by enteral feeding tube every six hours for 72 hours. | Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| F2-isoprostanes After 72 Hours of Acetaminophen or Placebo | F2-isoprostanes are a marker of oxidative stress, specifically lipid peroxidation. | 72 hours after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-hospital Mortality | percent of patients who died in the hospital | 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 | 72 hours |