CClinicalTrials.gg
Sign In
CompletedNCT00791648Updated Sep 16, 2019Results posted

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

An interventional study of atorvastatin and placebo in Acute Kidney Injury, Post-Operative Delirium and Icu Delirium, sponsored by Vanderbilt University Medical Center. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-09-16.

Sponsored by Vanderbilt University Medical Center · Not applicable, Interventional, and Prevention

Phase
Not applicable
Study type
Interventional
Enrollment
653
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Acute Kidney Injury
  • Post-Operative Delirium
  • Icu Delirium
  • Acute Renal Failure
  • Delirium

Keywords

  • aki
  • delirium
  • statin
  • short-term
  • cardiac
03

In context

Delirium

1,057 studies on the registry are indexed under Delirium; 238 are open to participants now.

This study's enrollment of 653 is above the median of 120 across 599 interventional studies indexed under Delirium.

Browse Delirium studies →

Lead sponsor

Vanderbilt University Medical Center is the lead sponsor of 824 studies on the registry; 164 are open to participants now.

Of its 122 completed or terminated interventional studies of FDA-regulated products, 91 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • open heart surgery

Exclusion criteria

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.
05

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
653 participants (actual)

Study arms

  • 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.

    Drug: atorvastatin

  • 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.

    Drug: placebo

Interventions

  • Drugatorvastatin

    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.

    Also known as: Lipitor

  • Drugplacebo

    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.

06

What researchers measure

Primary outcomes

  1. Number of Participants With Acute Kidney Injury

    Time frame: postoperative day 2

  2. Number of Participants With Delirium

    Time frame: while in ICU (about 2 days)

Secondary outcomes

  1. Number of Participants Requiring Dialysis

    Time frame: while in ICU (about 2 days)

  2. Liver Enzyme: Aspartate Aminotransferase Level

    Time frame: postoperative day 1

  3. Number of Participants With Stroke

    Time frame: while in ICU (about 2 days)

  4. Number of Participants That Died

    Time frame: until postoperative hospital discharge (about 7 days)

  5. Mitochondrial Function--mtDNA Copy Number

    mtDNA copy number

    Time frame: anesthesia induction and POD 1

  6. Mitochondrial Function--lactate / Pyruvate Ratio

    lactate / pyruvate ratio

    Time frame: anesthesia induction, after CPB, and POD 1

  7. Mitochondrial Function--PGC-1alpha RNA Expression

    PGC-1alpha RNA expression

    Time frame: anesthesia induction and POD 1

  8. Urine Markers of Renal Injury

    tissue inhibitor metaloproteinase-2 x insulin-like growth factor binding protein-7

    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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Plasma Markers of Inflammation: Measurements of Neuronal Injury (Ubiquitin C-terminal Hydrolase-1)

    measurements of neuronal injury (ubiquitin C-terminal hydrolase-1)

    Time frame: anesthesia induction, ICU admission, and POD 1

  14. Plasma Markers of Inflammation: Blood Brain Barrier Disruption (S100 Calcium-binding Protein B)

    measurements of blood brain barrier disruption (S100 calcium-binding protein B)

    Time frame: anesthesia induction, ICU admission, and POD 1

07

Results

Posted Mar 6, 2017

Participant flow

Participant flow — Overall Study
MilestoneStatinPlacebo
Started308309
Completed308307
Not completed02
Withdrew: Physician decision01
Withdrew: Withdrawal by subject01

Outcome measures

PrimaryNumber of Participants With Acute Kidney Injury
Time frame:
postoperative day 2
Reported as:
Count of participants · Participants
Number of Participants With Acute Kidney Injury
ParticipantsStatinPlacebo
Number of Participants With Acute Kidney Injury6460
Statistical analysis
  • Statin vs Placebo · Pearson x2 · p = .75
PrimaryNumber of Participants With Delirium
Time frame:
while in ICU (about 2 days)
Reported as:
Count of participants · Participants
Number of Participants With Delirium
ParticipantsStatinPlacebo
Number of Participants With Delirium6975
Statistical analysis
  • Statin vs Placebo · Wilcoxon (Mann-Whitney) · p = .56
SecondaryNumber of Participants Requiring Dialysis
Time frame:
while in ICU (about 2 days)
Reported as:
Count of participants · Participants
Number of Participants Requiring Dialysis
ParticipantsStatinPlacebo
Number of Participants Requiring Dialysis53
Statistical analysis
  • Statin vs Placebo · Wilcoxon (Mann-Whitney) · p = .71
SecondaryLiver Enzyme: Aspartate Aminotransferase Level
Time frame:
postoperative day 1
Reported as:
Median · units/liter
Liver Enzyme: Aspartate Aminotransferase Level
units/literStatinPlacebo
Liver Enzyme: Aspartate Aminotransferase Level49 (25 to 105)52 (27 to 146)
Statistical analysis
  • Statin vs Placebo · Wilcoxon (Mann-Whitney) · p = .11
SecondaryNumber of Participants With Stroke
Time frame:
while in ICU (about 2 days)
Reported as:
Count of participants · Participants
Number of Participants With Stroke
ParticipantsStatinPlacebo
Number of Participants With Stroke107
Statistical analysis
  • Statin · Wilcoxon (Mann-Whitney) · p = .06
SecondaryNumber of Participants That Died
Time frame:
until postoperative hospital discharge (about 7 days)
Reported as:
Count of participants · Participants
Number of Participants That Died
ParticipantsStatinPlacebo
Number of Participants That Died41
Statistical analysis
  • Statin vs Placebo · Wilcoxon (Mann-Whitney) · p = .39
SecondaryMitochondrial Function--mtDNA Copy Number

mtDNA copy number

Time frame:
anesthesia induction and POD 1
Reported as:
Median · au
Mitochondrial Function--mtDNA Copy Number
auStatinPlacebo
at anesthesia induction0.40 (0.19 to 0.99).48 (.21 to 1.1)
POD 10.3 (0.17 to 0.3)0.43 (0.17 to 0.88)
SecondaryMitochondrial Function--lactate / Pyruvate Ratio

lactate / pyruvate ratio

Time frame:
anesthesia induction, after CPB, and POD 1
Reported as:
Median · ratio
Mitochondrial Function--lactate / Pyruvate Ratio
ratioStatinPlacebo
at anesthesia induction0.04 (0.03 to 0.06)0.04 (0.03 to 0.06)
after CPB0.06 (0.03 to 0.09)0.06 (0.03 to 0.09)
POD 10.04 (0.03 to 0.05)0.04 (0.03 to 0.06)
SecondaryMitochondrial Function--PGC-1alpha RNA Expression

PGC-1alpha RNA expression

Time frame:
anesthesia induction and POD 1
Reported as:
Median · au
Mitochondrial Function--PGC-1alpha RNA Expression
auStatinPlacebo
at anesthesia induction0.54 (0.18 to 1.86)0.84 (0.23 to 2.51)
POD 11.02 (0.27 to 2.45)1.37 (0.54 to 3.88)
SecondaryUrine Markers of Renal Injury

tissue inhibitor metaloproteinase-2 x insulin-like growth factor binding protein-7

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
Reported as:
Median · (ng/ml)^2/1000
Urine Markers of Renal Injury
(ng/ml)^2/1000StatinPlacebo
at anesthesia induction0.119 (0.046 to 0.317)0.098 (0.037 to 0.262)
30 minutes into cardiopulmonary bypass (CPB)0.171 (0.062 to 0.442)0.169 (0.056 to 0.360)
after CPB0.218 (0.077 to 0.561)0.219 (0.087 to 0.619)
ICU admission0.096 (0.043 to 0.238)0.112 (0.043 to 0.285)
6 hours post-op0.210 (0.108 to 0.452)0.207 (0.084 to 0.438)
POD 10.189 (0.040 to 0.489)0.186 (0.061 to 0.499)
POD 20.170 (0.050 to 0.380)0.115 (0.048 to 0.328)
POD 30.134 (0.046 to 0.309)0.102 (0.054 to 0.287)
SecondaryPlasma 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.
Reported as:
Median · pg/ml
Plasma Markers of Oxidative Stress: f2-Isoprostanes
pg/mlStatinPlacebo
at anesthesia induction29.4 (20.1 to 41.1)28.8 (20.7 to 41)
30 minutes into cardiopulmonary bypass (CPB)41.6 (29.3 to 60.3)39 (27.2 to 57.4)
after CPB32.3 (23.6 to 46.8)31.5 (23.6 to 45)
ICU admission32.1 (22.1 to 42.4)31.6 (23.6 to 44.5)
6 hours post-op32.1 (26.7 to 42.4)41 (35.2 to 49)
POD 128.1 (21.5 to 39.4)30.2 (21.9 to 41.6)
POD 228.5 (21.7 to 50.5)37 (28 to 47.6)
POD 332.7 (27.9 to 54.3)26.5 (23.2 to 49.8)
SecondaryPlasma 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.
Reported as:
Median · pg/ml
Plasma Markers of Oxidative Stress: Isofurans
pg/mlStatinPlacebo
at anesthesia induction45 (32.9 to 70)48.4 (34.1 to 77.6)
30 minutes into cardiopulmonary bypass (CPB)59.9 (37.9 to 93.8)56.2 (42.1 to 89.4)
after CPB57.6 (41.1 to 83.8)60.6 (38.1 to 90.2)
ICU admission63.7 (45 to 92.4)64 (45.2 to 92.3)
6 hours post-op42.5 (22.5 to 63.9)40.4 (29.5 to 59.1)
POD 148 (32.1 to 82.5)50.9 (34.1 to 85.1)
POD 240 (22.8 to 59)36 (22 to 46)
POD 333.5 (25.3 to 53.9)38 (16.5 to 50.2)
SecondaryUrine 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.
Reported as:
Median · ng/mg creatinine
Urine Markers of Oxidative Stress: f2-Isoprostanes
ng/mg creatinineStatinPlacebo
at anesthesia induction1.369 (0.856 to 2.183)1.478 (0.836 to 2.237)
30 minutes into cardiopulmonary bypass (CPB)1.750 (0.948 to 2.718)2.29 (1.241 to 4.027)
after CPB2.71 (1.247 to 5.38)2.729 (1.719 to 4.889)
ICU admission1.816 (0.92 to 03.167)2.9 (1.85 to 5.71)
6 hours post-op1.464 (0.839 to 2.389)1.77 (1.190 to 3.510)
POD 11.056 (0.602 to 1.756)1.143 (0.634 to 1.924)
POD 20.792 (0.604 to 1.360)0.88 (0.7 to 1.548)
POD 30.870 (0.527 to 1.601)0.875 (0.812 to 1.235)
SecondaryUrine 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.
Reported as:
Median · (ng/ml)^2/1000
Urine Markers of Oxidative Stress: Isofurans
(ng/ml)^2/1000StatinPlacebo
at anesthesia induction2.146 (1.321 to 3.316)2.146 (1.321 to 3.316)
30 minutes into cardiopulmonary bypass (CPB)2.48 (1.545 to 3.18)2.48 (1.545 to 3.18)
after CPB3.709 (2.279 to 6.283)3.709 (2.279 to 6.283)
ICU admission3.734 (2.877 to 8.18)3.734 (2.877 to 8.18)
6 hours post-op3.310 (1.9 to 5.420)3.070 (1.912 to 5.99)
POD 12.344 (1.503 to 3.633)2.344 (1.503 to 3.633)
POD 22.2 (1.428 to 4.050)2.2 (1.428 to 4.05)
POD 32.16 (1.43 to 2.84)2.16 (1.43 to 2.840)
SecondaryPlasma Markers of Inflammation: Measurements of Neuronal Injury (Ubiquitin C-terminal Hydrolase-1)

measurements of neuronal injury (ubiquitin C-terminal hydrolase-1)

Time frame:
anesthesia induction, ICU admission, and POD 1
Reported as:
Median · ng/ml
Plasma Markers of Inflammation: Measurements of Neuronal Injury (Ubiquitin C-terminal Hydrolase-1)
ng/mlStatinPlacebo
at anesthesia induction6.2 (4.2 to 10)6.7 (4.1 to 10.2)
ICU admission12.3 (7.9 to 21.7)11.6 (8.0 to 23.9)
POD 112.8 (8.3 to 19.5)12.2 (8.5 to 17.9)
SecondaryPlasma Markers of Inflammation: Blood Brain Barrier Disruption (S100 Calcium-binding Protein B)

measurements of blood brain barrier disruption (S100 calcium-binding protein B)

Time frame:
anesthesia induction, ICU admission, and POD 1
Reported as:
Median · pg/ml
Plasma Markers of Inflammation: Blood Brain Barrier Disruption (S100 Calcium-binding Protein B)
pg/mlStatinPlacebo
at anesthesia induction17.5 (12.5 to 25)17 (11.5 to 23.1)
ICU admission163.9 (110.7 to 255.9)163.1 (97.3 to 278.5)
POD 146.1 (30.4 to 64.2)45 (32.7 to 67.9)

Adverse events

Collected over First 10 post-op days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Statin—14/308 (4.5%)308/308 (100%)
Placebo—19/307 (6.2%)307/307 (100%)
Most frequent serious events
Showing 10 of 16
Most frequent serious events
EventStatinPlacebo
Cardiac ArrestCardiac disorders5/3082/307
Severe InfectionInfections and infestations2/3084/307
Sternal DehiscenceSkin and subcutaneous tissue disorders0/3082/307
AspirationRespiratory, thoracic and mediastinal disorders0/3082/307
Severe Respiratory DistressRespiratory, thoracic and mediastinal disorders2/3081/307
Severe Peripheral Vascular IschemiaVascular disorders1/3081/307
HemothoraxRespiratory, thoracic and mediastinal disorders1/3081/307
Hemolytic AnemiaBlood and lymphatic system disorders0/3081/307
Fall with Factured HipInjury, poisoning and procedural complications0/3081/307
CoagulapathyBlood and lymphatic system disorders0/3081/307
Most frequent other events
Most frequent other events
EventStatinPlacebo
Decreased Cardiac OutputCardiac disorders187/308194/307
HypotensionCardiac disorders188/308192/307
AnemiaSurgical and medical procedures183/308172/307
LeukocytosisInfections and infestations141/308140/307
VasoplegiaCardiac disorders120/308118/307
Lactic AcidosisCardiac disorders55/30859/307
FeverInfections and infestations50/30852/307
TachycardiaCardiac disorders49/30842/307
TransaminemiaHepatobiliary disorders23/30839/307

Baseline characteristics

Age, Continuous
Age, Continuous(years)StatinPlaceboTotal
Median66 (49 to 81)67 (51 to 81)66 (49 to 81)
Sex: Female, Male
Sex: Female, Male(Participants)StatinPlaceboTotal
Female9494188
Male214213427
Region of Enrollment
Region of Enrollment(participants)StatinPlaceboTotal
United States308307615
08

Study locations

1 site
  • Vanderbilt University Medical Center
    Nashville, Tennessee 37212, United States
09

References and documents

Publications

  • 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. PubMed 29223955 ↗
  • 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. PubMed 26906014 ↗
  • 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. PubMed 21334433 ↗

Individual participant data

Plan to share: Yes — All study data that are necessary to assess the study hypotheses regarding the primary and secondary outcomes are available for sharing in a manner that protects the privacy of study participants.

Supporting information: Study protocol, Sap, Icf, Csr

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 16, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00791648
Lead sponsor
Vanderbilt University Medical Center
Responsible party
Frederic T Billings IV (Assistant Professor of Anesthesiology and Critical Care Medicine, Vanderbilt University Medical Center) — Principal investigator
First posted
Nov 14, 2008
Start date
Jul 2009
Primary completion
Oct 2014
Completion
Dec 2014
Results posted
Mar 6, 2017
Last update
Sep 16, 2019

Study contacts

Frederic T. Billings, IV, MD
principal investigator · Vanderbilt University

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Aug 2019. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Delirium→

Other studies from this sponsor

Vanderbilt University Medical Center

Start the discussion