Short-term Atorvastatin's Effect on Acute Kidney Injury Following Cardiac Surgery - Full Text View

Sponsor:	Vanderbilt University
Information provided by:	Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00791648

Purpose

Aim1a: Statin naive patient's scheduled for cardiac surgery will be randomized to 80mg atorvastatin or placebo on the day prior to surgery and then 40mg daily thereafter until hospital discharge to test the hypothesis that short-term atorvastatin use decreases:

acute kidney injury following cardiac surgery.
postoperative delirium following cardiac surgery.

Aim1b: Patients using statins preoperatively will be randomized to atorvastatin 80mg or placebo on day of surgery and 40mg or placebo on postop day 1 with resumption of preoperative statin therapy on postop day 2 to test the hypothesis that short-term atorvastatin use decreases:

acute kidney injury following cardiac surgery.
postoperative delirium following cardiac surgery.

Endpoints include glomerular filtration, urine and plasma markers of renal dysfunction, markers of oxidative stress, mitochondrial function, systemic inflammatory markers, delirium, dialysis, stroke, myocardial infarction, time to extubation, ICU length of stay, and death.

Condition	Intervention
Acute Kidney Injury Post-Operative Delirium Icu Delirium Acute Renal Failure Delirium	Drug: atorvastatin Drug: placebo

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	Short-term Atorvastatin's Effect on Acute Kidney Injury Following Cardiac Surgery

Resource links provided by NLM:

MedlinePlus related topics: Delirium Heart Surgery Statins Urine and Urination

Drug Information available for: Atorvastatin calcium

U.S. FDA Resources

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:

acute kidney injury [ Time Frame: at randomization, at anesthsia induction, and postoperative days 1, 2, and 3, up to 6 months. ] [ Designated as safety issue: No ]
delirium [ Time Frame: at randomization, daily postoperatively while in ICU, and up to 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

dialysis [ Time Frame: until postoperative ICU discharge. ] [ Designated as safety issue: No ]
urine markers of renal injury [ Time Frame: at randomization, anesthesia induction, 30 minutes into cardiopulm bypass (CPB), after CPB, ICU admission, 6 hours postop, 12 hours postop, and POD 1, 2, 3. ] [ Designated as safety issue: No ]
plasma markers of inflammation [ Time Frame: at randomization, anesthesia induction, 30 minutes into cardiopulm bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3. ] [ Designated as safety issue: No ]
liver enzymes [ Time Frame: postoperative day 1 ] [ Designated as safety issue: Yes ]
stroke [ Time Frame: until postoperative ICU discharge ] [ Designated as safety issue: No ]
death [ Time Frame: until postoperative hospital discharge & at 6 months ] [ Designated as safety issue: No ]
plasma and urine markers of oxidative stress (f2-Isoprostanes, isofurans) [ Time Frame: at randomization, anesthesia induction, 30 minutes into cardiopulm bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3. ] [ Designated as safety issue: No ]
mitochondrial function [ Time Frame: at randomization, anesthesia induction, 30 minutes into cardiopulm bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3. ] [ Designated as safety issue: No ]
mtDNA copy number, lactate / pyruvate ratio, PGC-1alpha RNA expression

Estimated Enrollment:	820
Study Start Date:	July 2009
Estimated Study Completion Date:	December 2012
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: statin	Drug: atorvastatin Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.
Placebo Comparator: placebo	Drug: placebo Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

open heart surgery

Exclusion Criteria:

acute coronary syndrome with troponin leak or unrelenting angina
liver dysfunction (transaminases 2x normal)
history of myopathy or liver dysfunction on prior statin therapy
use of potent CYP3A4 inhibitors such as antifungal azoles, macrolide antibiotics, HIV protease inhibitors, and nefazodone.
pregnancy or breast feeding
cyclosporine use
dialysis
history of kidney transplant
fibrate users who cannot stop fibrate use.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00791648

Contacts

Contact: Frederic T. Billings, IV, MD

615-936-8487

frederic.t.billings@vanderbilt.edu

Locations

United States, Tennessee
Vanderbilt University Medical Center	Recruiting
Nashville, Tennessee, United States, 37212
Contact: Frederic T. Billings, IV, MD 615-343-6479 frederic.t.billings@vanderbilt.edu

Sponsors and Collaborators

Vanderbilt University

Investigators

Principal Investigator:

Frederic T. Billings, IV, MD

Vanderbilt University

More Information

No publications provided by Vanderbilt University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Epub 2011 Feb 18.

Responsible Party:	Frederic T. Billings, IV, MD, Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00791648 History of Changes
Other Study ID Numbers:	081238
Study First Received:	November 12, 2008
Last Updated:	July 12, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by Vanderbilt University:

aki
delirium
statin
short-term
cardiac

Additional relevant MeSH terms:

Delirium
Acute Kidney Injury
Renal Insufficiency
Confusion
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Kidney Diseases

Urologic Diseases
Atorvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 23, 2012