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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:
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| atorvastatin | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Acute Kidney Injury | postoperative day 2 | |
| Number of Participants With Delirium | while in ICU (about 2 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Requiring Dialysis | while in ICU (about 2 days) | |
| Liver Enzyme: Aspartate Aminotransferase Level | postoperative day 1 | |
| Number of Participants With Stroke |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Frederic T. Billings, IV, MD | Vanderbilt University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical Center | Nashville | Tennessee | 37212 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29223955 | Derived | 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. | |
| 26906014 | Derived | 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. |
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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.
Data will become available within 6 weeks of request and will be available indefinitely.
These data will be made available upon reasonable request.
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36 patients consented patients were excluded prior to randomization
14 withdrew, 12 did not require surgery, 4 had unreported baseline live dysfunction, 2 developed acute coronary syndrome, 2 had statin intolerance, 1 died prior to study intervention and surgery, 1 enrolled in another drug study.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Acute Kidney Injury | Posted | Count of Participants | Participants | postoperative day 2 |
|
First 10 post-op days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac Arrest | Cardiac disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fever | Infections and infestations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Frederic Billings | Vanderbilt University | 615-343-6268 | frederic.t.billings@vanderbilt.edu |
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| ID | Term |
|---|---|
| D058186 | Acute Kidney Injury |
| D000071257 | Emergence Delirium |
| D003693 | Delirium |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D000069059 | Atorvastatin |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| placebo | Drug | 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. |
|
| while in ICU (about 2 days) |
| Number of Participants That Died | until postoperative hospital discharge (about 7 days) |
| Mitochondrial Function--mtDNA Copy Number | mtDNA copy number | anesthesia induction and POD 1 |
| Mitochondrial Function--lactate / Pyruvate Ratio | lactate / pyruvate ratio | anesthesia induction, after CPB, and POD 1 |
| Mitochondrial Function--PGC-1alpha RNA Expression | PGC-1alpha RNA expression | anesthesia induction and POD 1 |
| 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 |
| 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. |
| 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) | measurements of neuronal injury (ubiquitin C-terminal hydrolase-1) | 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) | anesthesia induction, ICU admission, and POD 1 |
| 21334433 | Derived | 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. |
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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|
| Participants |
|
|
|
| Primary | Number of Participants With Delirium | Posted | Count of Participants | Participants | while in ICU (about 2 days) |
|
|
|
|
| Secondary | Number of Participants Requiring Dialysis | Posted | Count of Participants | Participants | while in ICU (about 2 days) |
|
|
|
|
| Secondary | Liver Enzyme: Aspartate Aminotransferase Level | Posted | Median | 95% Confidence Interval | units/liter | postoperative day 1 |
|
|
|
|
| Secondary | Number of Participants With Stroke | Posted | Count of Participants | Participants | while in ICU (about 2 days) |
|
|
|
|
| Secondary | Number of Participants That Died | Posted | Count of Participants | Participants | until postoperative hospital discharge (about 7 days) |
|
|
|
|
| Secondary | Mitochondrial Function--mtDNA Copy Number | mtDNA copy number | This marker was only measured in a subset of the total study population, chosen at random. | Posted | Median | Inter-Quartile Range | au | anesthesia induction and POD 1 |
|
|
|
| Secondary | Mitochondrial Function--lactate / Pyruvate Ratio | lactate / pyruvate ratio | This marker was only measured in a subset of the total study population, chosen at random. | Posted | Median | Inter-Quartile Range | ratio | anesthesia induction, after CPB, and POD 1 |
|
|
|
| Secondary | Mitochondrial Function--PGC-1alpha RNA Expression | PGC-1alpha RNA expression | This marker was only measured in a subset of the total study population, chosen at random. | Posted | Median | Inter-Quartile Range | au | anesthesia induction and POD 1 |
|
|
|
| Secondary | Urine Markers of Renal Injury | tissue inhibitor metaloproteinase-2 x insulin-like growth factor binding protein-7 | This marker was only measured in a subset of the total study population, chosen at random. | Posted | Median | Inter-Quartile Range | (ng/ml)^2/1000 | 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 | This marker was only measured in a subset of the total study population, chosen at random. | Posted | Median | Inter-Quartile Range | pg/ml | 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 | This marker was only measured in a subset of the total study population, chosen at random. | Posted | Median | Inter-Quartile Range | pg/ml | 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 | This marker was only measured in a subset of the total study population, chosen at random. | Posted | Median | Inter-Quartile Range | ng/mg creatinine | 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 | This marker was only measured in a subset of the total study population, chosen at random. | Posted | Median | Inter-Quartile Range | (ng/ml)^2/1000 | 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) | This marker was only measured in a subset of the total study population, chosen at random. | Posted | Median | Inter-Quartile Range | ng/ml | 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) | This marker was only measured in a subset of the total study population, chosen at random. | Posted | Median | Inter-Quartile Range | pg/ml | anesthesia induction, ICU admission, and POD 1 |
|
|
|
| 14 |
| 308 |
| 308 |
| 308 |
| EG001 | 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. | 19 | 307 | 307 | 307 |
| Severe Infection | Infections and infestations | Systematic Assessment |
|
| Severe Peripheral Vascular Ischemia | Vascular disorders | Systematic Assessment |
|
| Sternal Dehiscence | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Hemothorax | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Severe Respiratory Distress | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Hemolytic Anemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| Severe Heart Failure | Cardiac disorders | Systematic Assessment |
|
| Fall with Factured Hip | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Aspiration | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Coagulapathy | Blood and lymphatic system disorders | Systematic Assessment |
|
| Cardiac Tamponade | Congenital, familial and genetic disorders | Systematic Assessment |
|
| Ileus | Gastrointestinal disorders | Systematic Assessment |
|
| Small Bowel Obstruction | Gastrointestinal disorders | Systematic Assessment |
|
| Intra-operative Injury to Blood Vessel | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Idiopathic Thrombocytopenia Purpura | Blood and lymphatic system disorders | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | Systematic Assessment |
|
| Hypotension | Cardiac disorders | Systematic Assessment |
|
| Vasoplegia | Cardiac disorders | Systematic Assessment |
|
| Decreased Cardiac Output | Cardiac disorders | Systematic Assessment | Cardiac Output was only measured in patients with a pulmonary artery catheter |
|
| Anemia | Surgical and medical procedures | Systematic Assessment |
|
| Leukocytosis | Infections and infestations | Systematic Assessment |
|
| Lactic Acidosis | Cardiac disorders | Systematic Assessment |
|
| Transaminemia | Hepatobiliary disorders | Systematic Assessment |
|
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| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D003221 | Confusion |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012816 | Signs and Symptoms |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D006538 |
| Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| POD 1 |
|
| after CPB |
|
| ICU admission |
|
| 6 hours post-op |
|
| POD 1 |
|
| POD 2 |
|
| POD 3 |
|
| after CPB |
|
| ICU admission |
|
| 6 hours post-op |
|
| POD 1 |
|
| POD 2 |
|
| POD 3 |
|
| after CPB |
|
| ICU admission |
|
| 6 hours post-op |
|
| POD 1 |
|
| POD 2 |
|
| POD 3 |
|
| after CPB |
|
| ICU admission |
|
| 6 hours post-op |
|
| POD 1 |
|
| POD 2 |
|
| POD 3 |
|
| after CPB |
|
| ICU admission |
|
| 6 hours post-op |
|
| POD 1 |
|
| POD 2 |
|
| POD 3 |
|
| POD 1 |
|
| POD 1 |
|