Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis

NCT01739361 | Completed Phase 2 Results DMC

• 1 other identifier: APAP-121486
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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.

Conditions

Severe Sepsis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• In-hospital Mortality

  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

  72 hours

Study Arms (2)

Acetaminophen

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Drug: placebo

Interventions

Acetaminophen DRUG

Acetaminophen

placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and Female \>=18 years old
• Admitted to an Intensive Care Unit
• Severe Sepsis
• Detectable plasma cell-free hemoglobin

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Sepsis

Interventions

Acetaminophen

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Results Point of Contact

• Title: Dr. David R Janz, MD, MSc, Assistant Professor of Medicine
• Organization: LSU Health Sciences Center New Orleans

djanz@lsuhsc.edu

504-568-3167

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 26, 2012
• First Posted: December 3, 2012
• Study Start: April 1, 2013
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: December 26, 2017
• Results First Posted: March 23, 2015

Record last verified: 2017-11

Locations

US (1)