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Inhibition of Lipid Peroxidation During Cardiac Surgery

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mias Pretorius, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01366976
First received: June 2, 2011
Last updated: June 12, 2013
Last verified: June 2013
History of Changes
  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: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Inhibition of Lipid Peroxidation During Cardiopulmonary Bypass

Resource links provided by NLM:

MedlinePlus related topics: Heart Surgery
U.S. FDA Resources

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Oxidative stress response [ Time Frame: 6 time points over 24 hours ] [ Designated as safety issue: No ]
    Oxidative stress response in both urine and plasma as measured by F2isoP and isoF concentrations


Secondary Outcome Measures:
  • Acute kidney injury [ Time Frame: 4 time points over 48 hours ] [ Designated as safety issue: No ]
    Changes in creatinine and NGAL


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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: 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:

Responsible Party: Mias Pretorius, Associate Professor, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01366976     History of Changes
Other Study ID Numbers: 110423
Study First Received: June 2, 2011
Last Updated: June 12, 2013
Health Authority: United States: Institutional Review Board

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

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

ClinicalTrials.gov processed this record on June 13, 2013