search
Back to results

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

Primary Purpose

Acute Kidney Injury, Post-Operative Delirium, Icu Delirium

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
atorvastatin
placebo
Sponsored by
Vanderbilt University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Acute Kidney Injury focused on measuring aki, delirium, statin, short-term, cardiac

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

statin

placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Number of Participants With Acute Kidney Injury
Number of Participants With Delirium

Secondary Outcome Measures

Number of Participants Requiring Dialysis
Liver Enzyme: Aspartate Aminotransferase Level
Number of Participants With Stroke
Number of Participants That Died
Mitochondrial Function--mtDNA Copy Number
mtDNA copy number
Mitochondrial Function--lactate / Pyruvate Ratio
lactate / pyruvate ratio
Mitochondrial Function--PGC-1alpha RNA Expression
PGC-1alpha RNA expression
Urine Markers of Renal Injury
tissue inhibitor metaloproteinase-2 x insulin-like growth factor binding protein-7
Plasma Markers of Oxidative Stress: f2-Isoprostanes
Plasma Markers of Oxidative Stress: Isofurans
Urine Markers of Oxidative Stress: f2-Isoprostanes
Urine Markers of Oxidative Stress: Isofurans
Plasma Markers of Inflammation: Measurements of Neuronal Injury (Ubiquitin C-terminal Hydrolase-1)
measurements of neuronal injury (ubiquitin C-terminal hydrolase-1)
Plasma Markers of Inflammation: Blood Brain Barrier Disruption (S100 Calcium-binding Protein B)
measurements of blood brain barrier disruption (S100 calcium-binding protein B)

Full Information

First Posted
November 12, 2008
Last Updated
August 29, 2019
Sponsor
Vanderbilt University Medical Center
search

1. Study Identification

Unique Protocol Identification Number
NCT00791648
Brief Title
Short-term Atorvastatin's Effect on Acute Kidney Injury Following Cardiac Surgery
Official Title
Short-term Atorvastatin's Effect on Acute Kidney Injury Following Cardiac Surgery
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University Medical Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Kidney Injury, Post-Operative Delirium, Icu Delirium, Acute Renal Failure, Delirium
Keywords
aki, delirium, statin, short-term, cardiac

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
653 (Actual)

8. Arms, Groups, and Interventions

Arm Title
statin
Arm Type
Experimental
Arm Description
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.
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
atorvastatin
Other Intervention Name(s)
Lipitor
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants With Acute Kidney Injury
Time Frame
postoperative day 2
Title
Number of Participants With Delirium
Time Frame
while in ICU (about 2 days)
Secondary Outcome Measure Information:
Title
Number of Participants Requiring Dialysis
Time Frame
while in ICU (about 2 days)
Title
Liver Enzyme: Aspartate Aminotransferase Level
Time Frame
postoperative day 1
Title
Number of Participants With Stroke
Time Frame
while in ICU (about 2 days)
Title
Number of Participants That Died
Time Frame
until postoperative hospital discharge (about 7 days)
Title
Mitochondrial Function--mtDNA Copy Number
Description
mtDNA copy number
Time Frame
anesthesia induction and POD 1
Title
Mitochondrial Function--lactate / Pyruvate Ratio
Description
lactate / pyruvate ratio
Time Frame
anesthesia induction, after CPB, and POD 1
Title
Mitochondrial Function--PGC-1alpha RNA Expression
Description
PGC-1alpha RNA expression
Time Frame
anesthesia induction and POD 1
Title
Urine Markers of Renal Injury
Description
tissue inhibitor metaloproteinase-2 x insulin-like growth factor binding protein-7
Time Frame
anesthesia induction, 30 minutes into cardiopulm bypass (CPB), after CPB, ICU admission, 6 hours postop, and Post op Day (POD) 1, 2, 3
Title
Plasma Markers of Oxidative Stress: f2-Isoprostanes
Time Frame
anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.
Title
Plasma Markers of Oxidative Stress: Isofurans
Time Frame
anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.
Title
Urine Markers of Oxidative Stress: f2-Isoprostanes
Time Frame
anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.
Title
Urine Markers of Oxidative Stress: Isofurans
Time Frame
anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.
Title
Plasma Markers of Inflammation: Measurements of Neuronal Injury (Ubiquitin C-terminal Hydrolase-1)
Description
measurements of neuronal injury (ubiquitin C-terminal hydrolase-1)
Time Frame
anesthesia induction, ICU admission, and POD 1
Title
Plasma Markers of Inflammation: Blood Brain Barrier Disruption (S100 Calcium-binding Protein B)
Description
measurements of blood brain barrier disruption (S100 calcium-binding protein B)
Time Frame
anesthesia induction, ICU admission, and POD 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Frederic T. Billings, IV, MD
Organizational Affiliation
Vanderbilt University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All study data that are necessary to assess the study hypotheses regarding the primary and secondary outcomes are available for sharing in a manner that protects the privacy of study participants.
IPD Sharing Time Frame
Data will become available within 6 weeks of request and will be available indefinitely.
IPD Sharing Access Criteria
These data will be made available upon reasonable request.
Citations:
PubMed Identifier
29223955
Citation
Smith LE, Smith DK, Blume JD, Linton MF, Billings FT 4th. High-Density Lipoprotein Cholesterol Concentration and Acute Kidney Injury After Cardiac Surgery. J Am Heart Assoc. 2017 Dec 9;6(12):e006975. doi: 10.1161/JAHA.117.006975.
Results Reference
derived
PubMed Identifier
26906014
Citation
Billings FT 4th, Hendricks PA, Schildcrout JS, Shi Y, Petracek MR, Byrne JG, Brown NJ. High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial. JAMA. 2016 Mar 1;315(9):877-88. doi: 10.1001/jama.2016.0548.
Results Reference
derived
PubMed Identifier
21334433
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs