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

Not Applicable

Completed

• Conditions: Post-Operative Delirium; Acute Kidney Injury; Icu Delirium; Delirium; Acute Renal Failure
• Interventions: Drug: placebo; Drug: atorvastatin

• Registration Number: NCT00791648
• Lead Sponsor: Vanderbilt University Medical Center

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:

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2008-11-12
• Study First Submitted QC: 2008-11-13
• Study First Posted: 2008-11-14
• Study Start: 2009-07
• Primary Completion: 2014-10
• Study Completion: 2014-12
• Results First Submitted: 2016-11-11
• Results First Submitted QC: 2017-01-11
• Results First Posted: 2017-03-06
• Status Verified: 2019-08
• Last Update Submitted: 2019-08-29
• Last Update Posted: 2019-09-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 653

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	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.
statin	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Acute Kidney Injury	postoperative day 2
Number of Participants With Delirium	while in ICU (about 2 days)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States