Clinical trial NCT00791648: 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
Overall status: COMPLETED
Phase: NA
Conditions: Acute Kidney Injury
Post-Operative Delirium
Icu Delirium
Acute Renal Failure
Delirium
Keywords: aki
delirium
statin
short-term
cardiac
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2008-11-14
Enrollment: 653
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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.

Primary outcomes:
measure: Number of Participants With Acute Kidney Injury
timeFrame: postoperative day 2
measure: Number of Participants With Delirium
timeFrame: while in ICU (about 2 days)
Secondary outcomes:
measure: Number of Participants Requiring Dialysis
timeFrame: while in ICU (about 2 days)
measure: Liver Enzyme: Aspartate Aminotransferase Level
timeFrame: postoperative day 1
measure: Number of Participants With Stroke
timeFrame: while in ICU (about 2 days)
measure: Number of Participants That Died
timeFrame: until postoperative hospital discharge (about 7 days)
measure: Mitochondrial Function--mtDNA Copy Number
timeFrame: anesthesia induction and POD 1
measure: Mitochondrial Function--lactate / Pyruvate Ratio
timeFrame: anesthesia induction, after CPB, and POD 1
measure: Mitochondrial Function--PGC-1alpha RNA Expression
timeFrame: anesthesia induction and POD 1
measure: Urine Markers of Renal Injury
timeFrame: anesthesia induction, 30 minutes into cardiopulm bypass (CPB), after CPB, ICU admission, 6 hours postop, and Post op Day (POD) 1, 2, 3
measure: Plasma Markers of Oxidative Stress: f2-Isoprostanes
timeFrame: anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.
measure: Plasma Markers of Oxidative Stress: Isofurans
timeFrame: anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.
measure: Urine Markers of Oxidative Stress: f2-Isoprostanes
timeFrame: anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.
measure: Urine Markers of Oxidative Stress: Isofurans
timeFrame: anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.
measure: Plasma Markers of Inflammation: Measurements of Neuronal Injury (Ubiquitin C-terminal Hydrolase-1)
timeFrame: anesthesia induction, ICU admission, and POD 1
measure: Plasma Markers of Inflammation: Blood Brain Barrier Disruption (S100 Calcium-binding Protein B)
timeFrame: anesthesia induction, ICU admission, and POD 1
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University
name: Frederic T. Billings, IV, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.