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

Acute Kidney Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00791648
• Other study ID #: 081238
• Status: Completed
• Phase: N/A
• Start date: July 2009
• Est. completion date: December 2014

Study information

• Verified date: August 2019
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 653
• Est. completion date: December 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Acute Renal Failure
• Delirium
• Icu Delirium
• Post-Operative Delirium
• Wounds and Injuries

Intervention

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
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.

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Acute Kidney Injury		postoperative day 2
Primary	Number of Participants With Delirium		while in ICU (about 2 days)
Secondary	Number of Participants Requiring Dialysis		while in ICU (about 2 days)
Secondary	Liver Enzyme: Aspartate Aminotransferase Level		postoperative day 1
Secondary	Number of Participants With Stroke		while in ICU (about 2 days)
Secondary	Number of Participants That Died		until postoperative hospital discharge (about 7 days)
Secondary	Mitochondrial Function--mtDNA Copy Number	mtDNA copy number	anesthesia induction and POD 1
Secondary	Mitochondrial Function--lactate / Pyruvate Ratio	lactate / pyruvate ratio	anesthesia induction, after CPB, and POD 1
Secondary	Mitochondrial Function--PGC-1alpha RNA Expression	PGC-1alpha RNA expression	anesthesia induction and POD 1
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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