NCT01366976

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
67

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Jul 2011

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 2, 2011

Completed
4 days until next milestone

First Posted

Study publicly available on registry

June 6, 2011

Completed
25 days until next milestone

Study Start

First participant enrolled

July 1, 2011

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2013

Completed
1.6 years until next milestone

Results Posted

Study results publicly available

January 14, 2015

Completed
Last Updated

January 27, 2015

Status Verified

January 1, 2015

Enrollment Period

1.9 years

First QC Date

June 2, 2011

Results QC Date

January 6, 2015

Last Update Submit

January 14, 2015

Conditions

Cardiopulmonary Bypass Induced Lipid Peroxidation

Keywords

oxidative stresscardiopulmonary bypassacetaminophenhemolysis

Outcome Measures

Primary Outcomes (2)

  • Plasma Isofuran Concentrations

    Plasma isofuran concentrations as a measure of lipid peroxidation

    24 hours

  • Plasma F2-isoprostane Concentrations

    Plasma F2-isoprostane concentrations as a measure of lipid peroxidation

    24 hours

Secondary Outcomes (2)

  • Urinary NGAL (Neutrophil Gelatinase-associated Lipocalin)

    24 hours

  • Serum Creatinine

    72 hours

Study Arms (2)

Placebo

PLACEBO COMPARATOR
Drug: Acetaminophen

Acetaminophen

ACTIVE COMPARATOR

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

Drug: Acetaminophen

Interventions

AcetaminophenDRUG

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

Also known as: Tylenol
AcetaminophenPlacebo

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (3)

  • 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.

    PMID: 21334433BACKGROUND

  • 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.

    PMID: 20133658BACKGROUND

  • 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.

    PMID: 25705899DERIVED

MeSH Terms

Conditions

Hemolysis

Interventions

Acetaminophen

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

AcetanilidesAnilidesAmidesOrganic ChemicalsAniline CompoundsAmines

Limitations and Caveats

The exploratory analysis of acute kidney injury (AKI) was limited by the low incidence of postoperative AKI in the current study, so we were underpowered to detect small differences in creatinine or NGAL concentrations.

Results Point of Contact

Title
Mias Pretorius
Organization
Vanderbilt University School of Medicine
mias.pretorius@vanderbilt.edu
16153220758

Study Officials

  • Mias Pretorius, MBChB, MSCI

    Vanderbilt University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
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
Associate Professor

Study Record Dates

First Submitted

June 2, 2011

First Posted

June 6, 2011

Study Start

July 1, 2011

Primary Completion

June 1, 2013

Study Completion

June 1, 2013

Last Updated

January 27, 2015

Results First Posted

January 14, 2015

Record last verified: 2015-01

Locations

US(1)