Severe Sepsis
Conditions
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.
Interventions
DRUGAcetaminophen
DRUGplacebo
Sponsors
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| F2-isoprostanes After 72 Hours of Acetaminophen or Placebo | 72 hours after randomization | F2-isoprostanes are a marker of oxidative stress, specifically lipid peroxidation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| In-hospital Mortality | Patients will be followed through the end of their hospital stay, an average of 5 weeks | percent of patients who died in the hospital |
| Serum Creatinine After 72 Hours of Treatment With Acetaminophen or Placebo | 72 hours | serum creatinine measurements at 72 hours |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Acetaminophen | 18 |
| Placebo Patients will receive placebo by mouth or by enteral feeding tube every six hours for 72 hours.
placebo | 22 |
| Total | 40 |
Baseline characteristics
| Characteristic | Acetaminophen | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 50 years | 58.5 years | 55.5 years |
| Sex: Female, Male Female | 9 Participants | 10 Participants | 19 Participants |
| Sex: Female, Male Male | 9 Participants | 12 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 21 | 0 / 23 |
| serious Total, serious adverse events | 2 / 21 | 1 / 23 |
Outcome results
Primary
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acetaminophen | F2-isoprostanes After 72 Hours of Acetaminophen or Placebo | 33.4 pg/mL |
| Placebo | F2-isoprostanes After 72 Hours of Acetaminophen or Placebo | 40.15 pg/mL |
p-value: 0.353Wilcoxon (Mann-Whitney)
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acetaminophen | In-hospital Mortality | 1 Participants |
| Placebo | In-hospital Mortality | 4 Participants |
Secondary
Serum Creatinine After 72 Hours of Treatment With Acetaminophen or Placebo
serum creatinine measurements at 72 hours
Time frame: 72 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acetaminophen | Serum Creatinine After 72 Hours of Treatment With Acetaminophen or Placebo | 1.04 mg/dL |
| Placebo | Serum Creatinine After 72 Hours of Treatment With Acetaminophen or Placebo | 1.36 mg/dL |