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Completed

NCT Number: NCT01366976

Inhibition of Lipid Peroxidation During Cardiac Surgery

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.

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Key information

Conditions

Cardiopulmonary Bypass Induced Lipid Peroxidation Hemolysis Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Subjects, 18 to 80 years of age, scheduled for elective cardiac surgery requiring CPB
  • 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

  • Allergic reaction to ApAP (acetaminophen)
  • Evidence of severe hepatic impairment (history of liver cirrhosis or total bilirubin >2.0mg/dl)
  • Impaired renal function (serum creatinine >2.0 mg/dl)
  • Emergency surgery
  • Pregnancy
  • Breast-feeding
  • 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
  • History of alcohol or drug abuse
  • Treatment with any investigational drug in the 1 month preceding the study
  • Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
  • Inability to comply with the protocol, e.g. uncooperative attitude and unlikelihood of completing the study
  • History or evidence of active asthma

Treatment and study plan

Acetaminophen

Drug

Acetaminophen 1g every 6 hours for 4 doses over 24 hours

Other names: Tylenol

Primary outcomes

  1. Plasma Isofuran Concentrations

    Time frame: 24 hours

    Plasma isofuran concentrations as a measure of lipid peroxidation

  2. Plasma F2-isoprostane Concentrations

    Time frame: 24 hours

    Plasma F2-isoprostane concentrations as a measure of lipid peroxidation

Secondary outcomes

  1. Urinary NGAL (Neutrophil Gelatinase-associated Lipocalin)

    Time frame: 24 hours

    Changes in urinary NGAL (neutrophil gelatinase-associated lipocalin) as marker of acute kidney injury

  2. Serum Creatinine

    Time frame: 72 hours

    Serum creatinine measured over a 72 hour period

Sponsors and collaborators

Lead sponsor

Vanderbilt University

Other

Registry information

Official study title

Inhibition of Lipid Peroxidation During Cardiopulmonary Bypass

Important dates

Study start
2011
Primary completion
2013
Study completion
2013
First posted
Jun 6, 2011
Registry last updated
Jan 27, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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