Inhibition of Lipid Peroxidation During Cardiac Surgery

NCT ID: NCT01366976

Last Updated: 2015-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2013-06-30

Brief Summary

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.

Conditions

Cardiopulmonary Bypass Induced Lipid Peroxidation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Group Type: PLACEBO_COMPARATOR

Acetaminophen

Intervention Type: DRUG

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

Acetaminophen

Acetaminophen will ge given as 1g every 6 hours for 4 doses over a 24 hours study period

Group Type: ACTIVE_COMPARATOR

Acetaminophen

Intervention Type: DRUG

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

Interventions

Acetaminophen

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

Intervention Type: DRUG

Other Intervention Names

Tylenol

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vanderbilt University

OTHER

Sponsor Role: lead

Responsible Party

Mias Pretorius

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mias Pretorius, MBChB, MSCI

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

References

Billings FT 4th, Ball SK, Roberts LJ 2nd, Pretorius M. Postoperative acute kidney injury is associated with hemoglobinemia and an enhanced oxidative stress response. Free Radic Biol Med. 2011 Jun 1;50(11):1480-7. doi: 10.1016/j.freeradbiomed.2011.02.011. Epub 2011 Feb 18.

Reference Type: BACKGROUND

PMID: 21334433 (View on PubMed)

Boutaud O, Moore KP, Reeder BJ, Harry D, Howie AJ, Wang S, Carney CK, Masterson TS, Amin T, Wright DW, Wilson MT, Oates JA, Roberts LJ 2nd. Acetaminophen inhibits hemoprotein-catalyzed lipid peroxidation and attenuates rhabdomyolysis-induced renal failure. Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2699-704. doi: 10.1073/pnas.0910174107. Epub 2010 Feb 1.

Reference Type: BACKGROUND

PMID: 20133658 (View on PubMed)

Billings FT 4th, Petracek MR, Roberts LJ 2nd, Pretorius M. Perioperative intravenous acetaminophen attenuates lipid peroxidation in adults undergoing cardiopulmonary bypass: a randomized clinical trial. PLoS One. 2015 Feb 23;10(2):e0117625. doi: 10.1371/journal.pone.0117625. eCollection 2015.

Reference Type: DERIVED

PMID: 25705899 (View on PubMed)

Other Identifiers

110423

Identifier Type: -

Identifier Source: org_study_id