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

Overview

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: 1. acute kidney injury following cardiac surgery. 2. 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: 1. acute kidney injury following cardiac surgery. 2. 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.

Full Title of Study: “Short-term Atorvastatin’s Effect on Acute Kidney Injury Following Cardiac Surgery”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: October 2014

Interventions

  • 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.
  • 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.

Arms, Groups and Cohorts

  • Experimental: statin
    • 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
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Number of Participants With Acute Kidney Injury
    • Time Frame: postoperative day 2
  • Number of Participants With Delirium
    • Time Frame: while in ICU (about 2 days)

Secondary Measures

  • Number of Participants Requiring Dialysis
    • Time Frame: while in ICU (about 2 days)
  • Liver Enzyme: Aspartate Aminotransferase Level
    • Time Frame: postoperative day 1
  • Number of Participants With Stroke
    • Time Frame: while in ICU (about 2 days)
  • Number of Participants That Died
    • Time Frame: until postoperative hospital discharge (about 7 days)
  • Mitochondrial Function–mtDNA Copy Number
    • Time Frame: anesthesia induction and POD 1
    • mtDNA copy number
  • Mitochondrial Function–lactate / Pyruvate Ratio
    • Time Frame: anesthesia induction, after CPB, and POD 1
    • lactate / pyruvate ratio
  • Mitochondrial Function–PGC-1alpha RNA Expression
    • Time Frame: anesthesia induction and POD 1
    • PGC-1alpha RNA expression
  • Urine Markers of Renal Injury
    • 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
    • tissue inhibitor metaloproteinase-2 x insulin-like growth factor binding protein-7
  • 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.
  • 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.
  • 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.
  • 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.
  • Plasma Markers of Inflammation: Measurements of Neuronal Injury (Ubiquitin C-terminal Hydrolase-1)
    • Time Frame: anesthesia induction, ICU admission, and POD 1
    • measurements of neuronal injury (ubiquitin C-terminal hydrolase-1)
  • Plasma Markers of Inflammation: Blood Brain Barrier Disruption (S100 Calcium-binding Protein B)
    • Time Frame: anesthesia induction, ICU admission, and POD 1
    • measurements of blood brain barrier disruption (S100 calcium-binding protein B)

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Vanderbilt University Medical Center
  • Provider of Information About this Clinical Study
    • Principal Investigator: Frederic T Billings IV, Assistant Professor of Anesthesiology and Critical Care Medicine – Vanderbilt University Medical Center
  • Overall Official(s)
    • Frederic T. Billings, IV, MD, Principal Investigator, Vanderbilt University

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