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Inhibition of Lipid Peroxidation During Cardiac Surgery

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01366976
First Posted: June 6, 2011
Last Update Posted: January 27, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Mias Pretorius, Vanderbilt University
  Purpose
Acute kidney injury is a major complication of cardiac surgery requiring cardiopulmonary bypass (CPB). Hemolysis and rhabdomyolysis frequently occur during CPB. Hemolysis leads to an increase in free hemoglobin, whereas rhabdomyolysis leads to an increase in myoglobin. Free plasma hemoglobin and myoglobin have been shown to be independent predictors of the acute kidney injury that results from CPB. When these hemeproteins are released into the plasma, they undergo redox cycling, generating radical species that initiate lipid peroxidation and a cascade of oxidative damage to cellular membranes, notably in the kidney. F2-isoprostanes and isofurans are sensitive and specific markers of oxidative stress in vivo, and are increased after CPB, particularly in those patients with acute kidney injury. Acetaminophen inhibits the lipid peroxidation catalyzed by myoglobin and hemoglobin. Moreover, in an animal model of rhabdomyolysis-induced kidney injury, acetaminophen significantly attenuated the decrease in creatinine clearance compared to control. The current proposal tests the central hypothesis that acetaminophen will attenuate the lipid peroxidation associated with the hemolysis and rhabdomyolysis that occur in patients undergoing CPB. Demonstration that acetaminophen inhibits the lipid peroxidation resulting from CPB would provide a rationale for a prospective randomized trial to test the hypothesis that acetaminophen will reduce the acute kidney injury that results from CPB.

Condition Intervention
Cardiopulmonary Bypass Induced Lipid Peroxidation Drug: Acetaminophen

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Inhibition of Lipid Peroxidation During Cardiopulmonary Bypass

Resource links provided by NLM:


Further study details as provided by Mias Pretorius, Vanderbilt University:

Primary Outcome Measures:
  • Plasma Isofuran Concentrations [ Time Frame: 24 hours ]
    Plasma isofuran concentrations as a measure of lipid peroxidation

  • Plasma F2-isoprostane Concentrations [ Time Frame: 24 hours ]
    Plasma F2-isoprostane concentrations as a measure of lipid peroxidation


Secondary Outcome Measures:
  • Urinary NGAL (Neutrophil Gelatinase-associated Lipocalin) [ Time Frame: 24 hours ]
    Changes in urinary NGAL (neutrophil gelatinase-associated lipocalin) as marker of acute kidney injury

  • Serum Creatinine [ Time Frame: 72 hours ]
    Serum creatinine measured over a 72 hour period


Enrollment: 67
Study Start Date: July 2011
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Acetaminophen
Acetaminophen 1g every 6 hours for 4 doses over 24 hours
Other Name: Tylenol
Active Comparator: Acetaminophen
Acetaminophen will ge given as 1g every 6 hours for 4 doses over a 24 hours study period
Drug: Acetaminophen
Acetaminophen 1g every 6 hours for 4 doses over 24 hours
Other Name: Tylenol

  Eligibility

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects, 18 to 80 years of age, scheduled for elective cardiac surgery requiring CPB
  2. For female subjects, the following conditions must be met:

postmenopausal for at least 1 year, or status-post surgical sterilization, or if of childbearing potential, utilizing adequate birth control and a negative urine beta-hcg prior to drug treatment

Exclusion Criteria:

  1. Allergic reaction to ApAP (acetaminophen)
  2. Evidence of severe hepatic impairment (history of liver cirrhosis or total bilirubin >2.0mg/dl)
  3. Impaired renal function (serum creatinine >2.0 mg/dl)
  4. Emergency surgery
  5. Pregnancy
  6. Breast-feeding
  7. Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult
  8. History of alcohol or drug abuse
  9. Treatment with any investigational drug in the 1 month preceding the study
  10. Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
  11. Inability to comply with the protocol, e.g. uncooperative attitude and unlikelihood of completing the study
  12. History or evidence of active asthma
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01366976


Locations
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Mias Pretorius, MBChB, MSCI Vanderbilt University
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mias Pretorius, Associate Professor, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01366976     History of Changes
Other Study ID Numbers: 110423
First Submitted: June 2, 2011
First Posted: June 6, 2011
Results First Submitted: January 6, 2015
Results First Posted: January 14, 2015
Last Update Posted: January 27, 2015
Last Verified: January 2015

Keywords provided by Mias Pretorius, Vanderbilt University:
oxidative stress
cardiopulmonary bypass
acetaminophen
hemolysis

Additional relevant MeSH terms:
Acetaminophen
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antipyretics