Acute Kidney InjuryNCT00791648
Short-term Atorvastatin's Effect on Acute Kidney Injury Following Cardiac Surgery
A study testing atorvastatin in people with Acute Kidney Injury and Post-Operative Delirium, run by Vanderbilt University Medical Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Kidney Injury, Post-Operative Delirium, Icu Delirium
- What is being tested?
- atorvastatin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 653 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2009to Dec 2014
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- open heart surgery
Who cannot join
- 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
Show all 9Show fewer
- dialysis
- history of kidney transplant
- fibrate users who cannot stop fibrate use.
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37212
About this study
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.
Read more
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.
- Being tested
- atorvastatin, placebo
- Keywords
- aki, delirium, statin, short-term, cardiac
- Medical subject headings
- Acute Kidney Injury, Emergence Delirium, Delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
atorvastatinDrug
Also called Lipitor
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.
placeboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| statin | Experimental | 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. Receives: Drug: atorvastatin |
| placebo | Placebo comparator | 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. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Acute Kidney Injury
Measured: postoperative day 2
Number of Participants With Delirium
Measured: while in ICU (about 2 days)
Secondary outcomes (14)
Number of Participants Requiring Dialysis
Measured: while in ICU (about 2 days)
Liver Enzyme: Aspartate Aminotransferase Level
Measured: postoperative day 1
Number of Participants With Stroke
Measured: while in ICU (about 2 days)
Number of Participants That Died
Measured: until postoperative hospital discharge (about 7 days)
Mitochondrial Function--mtDNA Copy Number
mtDNA copy number
Measured: anesthesia induction and POD 1
Mitochondrial Function--lactate / Pyruvate Ratio
lactate / pyruvate ratio
Measured: anesthesia induction, after CPB, and POD 1
Mitochondrial Function--PGC-1alpha RNA Expression
PGC-1alpha RNA expression
Measured: anesthesia induction and POD 1
Urine Markers of Renal Injury
tissue inhibitor metaloproteinase-2 x insulin-like growth factor binding protein-7
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: 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)
Measured: anesthesia induction, ICU admission, and POD 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2008 (estimated)
- Study startJul 2009
- Primary completionOct 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute Kidney InjuryStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 653 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Frederic T Billings IV, Vanderbilt University Medical Center
- Investigators
- Frederic T. Billings, IV, MD, Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00791648
- Sponsor's protocol ID
- 081238
- Status last verified
- Aug 2019
- First submitted
- 12 Nov 2008
- Last updated
- 16 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- 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.
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 29223955Billings 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 26906014Billings 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
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short-term Atorvastatin's Effect on Acute Kidney Injury Following Cardiac Surgery
- ClinicalTrials.gov ID
- NCT00791648
- Acronym / sponsor ID
- 081238
- Keywords
- aki, delirium, statin, short-term, cardiac
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 653 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- Jul 2009
- Primary completion
- Oct 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 14 Nov 2008 (estimated)
- Results
- Posted 6 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| statin | Experimental | Drug: atorvastatinAim1 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 | Placebo comparator | Drug: placeboAim 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- open heart surgery
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| atorvastatinAlso: LipitorAim1 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 | statin |
| placeboAim 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 |
Primary outcome
Number of Participants With Acute Kidney Injury
Time frame: postoperative day 2
Number of Participants With Delirium
Time frame: while in ICU (about 2 days)
14 secondary outcomes
Number of Participants Requiring Dialysis
Time frame: while in ICU (about 2 days)
Liver Enzyme: Aspartate Aminotransferase Level
Time frame: postoperative day 1
Number of Participants With Stroke
Time frame: while in ICU (about 2 days)
Number of Participants That Died
Time frame: until postoperative hospital discharge (about 7 days)
Mitochondrial Function--mtDNA Copy Number
Time frame: anesthesia induction and POD 1
Mitochondrial Function--lactate / Pyruvate Ratio
Time frame: anesthesia induction, after CPB, and POD 1
Mitochondrial Function--PGC-1alpha RNA Expression
Time frame: anesthesia induction and POD 1
Urine Markers of Renal Injury
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
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.
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.
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.
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.
Plasma Markers of Inflammation: Measurements of Neuronal Injury (Ubiquitin C-terminal Hydrolase-1)
Time frame: anesthesia induction, ICU admission, and POD 1
Plasma Markers of Inflammation: Blood Brain Barrier Disruption (S100 Calcium-binding Protein B)
Time frame: anesthesia induction, ICU admission, and POD 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29223955Smith 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.
- Derived from this study: PubMed 26906014Billings 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.
- Derived from this study: PubMed 21334433Billings 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.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frederic T. Billings, IV, MD principal investigator
Vanderbilt University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing atorvastatin in people with Acute Kidney Injury and Post-Operative Delirium, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Acute Kidney Injury (time frame: postoperative day 2). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00791648, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2019.