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

Study Overview
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Brief Summary
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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.

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

Conditions
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Acute Kidney Injury, Post-Operative Delirium, Icu Delirium, Acute Renal Failure, Delirium

Intervention / Treatment
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* Drug: atorvastatin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: statin<br>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: atorvastatin<br>* 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.<br>* Other names: Lipitor;|
| Placebo Comparator: placebo<br>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. | Drug: placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Acute Kidney Injury |  | postoperative day 2 | 
| Number of Participants With Delirium |  | while in ICU (about 2 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Requiring Dialysis |  | while in ICU (about 2 days) | 
| Liver Enzyme: Aspartate Aminotransferase Level |  | postoperative day 1 | 
| Number of Participants With Stroke |  | while in ICU (about 2 days) | 
| Number of Participants That Died |  | until postoperative hospital discharge (about 7 days) | 
| Mitochondrial Function--mtDNA Copy Number | mtDNA copy number | anesthesia induction and POD 1 | 
| Mitochondrial Function--lactate / Pyruvate Ratio | lactate / pyruvate ratio | anesthesia induction, after CPB, and POD 1 | 
| Mitochondrial Function--PGC-1alpha RNA Expression | PGC-1alpha RNA expression | anesthesia induction and POD 1 | 
| Urine Markers of Renal Injury | tissue inhibitor metaloproteinase-2 x insulin-like growth factor binding protein-7 | anesthesia induction, 30 minutes into cardiopulm bypass (CPB), after CPB, ICU admission, 6 hours postop, and Post op Day (POD) 1, 2, 3 | 
| Plasma Markers of Oxidative Stress: f2-Isoprostanes |  | 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 |  | 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 |  | 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 |  | 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) | measurements of neuronal injury (ubiquitin C-terminal hydrolase-1) | anesthesia induction, ICU admission, and POD 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) | anesthesia induction, ICU admission, and POD 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aki, delirium, statin, short-term, cardiac