Safety and Efficiency Study of Loading Dose Atorvastatin in Cardiac Surgery

Study Overview
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Brief Summary
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Statins were reported to have pleiotropic effects including antiinflammatory, anti-oxidative stress effects and stabilise plaque in some conditions. Some researches indicate loading dose statin can reduce contrast induced nephropathy, and the levels of inflammatory markers were significantly decreased. The investigators hypothesis loading dose atorvastatin may attenuate inflammatory response during cardiopulmonary bypass (CPB) and therefore reduce postoperative acute kidney injury in cardiac surgery.

Detailed Description
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Acute kidney injury occurs up to 30% in cardiac surgery which influenced patients' mid-term and long-term outcomes. Furthermore, evidence shows patients who initiate renal placement therapy in hospital have higher mortality and morbility. The pathologies of Cardiac surgery-associated acute kidney injury (CSA-AKI) is not clear yet ,many researches find cardiopulmonary bypass is an independent risk factor in developing AKI, and inflammatory bursts during cardiopulmonary bypass (CPB) may play an important role in CSA-AKI. Statins are reported to have anti-inflammatory reaction in many researches. In Some multicenter RCTS, Statins are reported to reduce myocardial infarction,atrial fibrillation and have renoprotective effects due to pleiotropic effects in percutaneous coronary intervention. While in the cardiac surgery settings, the renoprotective effect of statin is still controversial. The investigators believe the differences between surgery and PCI may contribute to the discrepancy. The investigators plan to test the renoprotective effect of atorvastatin in a randomized,double-blind control manner and try to explore the mechanism of this protective effect. The investigators hypothesise loading dose atorvastatin pretreatment in elective coronary artery bypass grafting surgery may attenuate inflammatory response in CPB and therefore reduce postoperative AKI or help recovery from AKI. The investigators randomize patients into two arms, the Atorvastatin group takes Atorvastatin 80mg 12h before surgery with another 40mg 2h before operation, the control arm takes placebo in the same regime. The investigators plan to compare the inflammatory cytokines at different time points and the incidence of AKI between the two groups. The investigators hope Atorvastatin group can decrease AKI incidence and has a lower level of inflammatory cytokines, what's more, the two have a good correlation in the time frame.

Official Title
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Anti-inflammatory and Renoprotective Effect of Pretreatment Loading Dose Atorvastatin in CABG

Conditions
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Acute Kidney Injury

Intervention / Treatment
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* Drug: Atorvastatin(Lipitor)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age > 18 years old elective coronary artery bypass surgery in CPB Exclusion Criteria: emergent surgery re-operation acute kidney dysfunction chronic kidney disease GFR < 60ml/min liver dysfunction existing myopathy LEVF < 40% statin allergic or contradictive pregnancy breast feed period

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atorvastatin<br>participants take 80mg Atorvastatin orally 12h before surgery with another 40mg 2h before surgery | Drug: Atorvastatin(Lipitor)<br>* participants take 80mg Atorvastatin orally 12h before surgery with another 40mg 2h before surgery<br>* Other names: Lipitor;|
| Placebo Comparator: Control<br>Participants randomized to Control arm take 80mg placebo 12h before surgery with another 40mg 2h before surgery | Drug: Placebo<br>* Participants randomized to Control arm take 80mg placebo 12h before surgery with another 40mg 2h before surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| acute kidney injury | Proportion developing AKI using AKIN criteria(stage 1,stage 2, stage3).we plan to measure serum creatinine in baseline, ICU admission,postoperative 6h、Day 1、Day 2 and Day 3.If multiple SCr was measured in one day ,then the highest value will be recorded.Also, we measure creatinine clearance via Cock-croft-Gault formula. | 72 hours after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of inflammatory biomarkers | we plan to measure IL-6,IL-10,TNF-α and hsCRP at 6 time points: before surgery、after chest closure、postOp.6h、12h、24h and 48h.Compare levels of cytokines between the two arms | 48h after surgery | 
| Requirement of renal replacement therapy | proportion need renal replacement therapy in hospital | participants will be followed for the duration of hospital stay , an expected average of 2 weeks | 
| liver function | liver dysfunction defined as transaminase>3UNL normal level | participants will be followed for the duration of hospital stay , an expected average of 2 weeks | 
| death |  | 30 days after discharge from hospital | 
| MACCE events |  | 30 days after discharge from hospital | 
| length of stay in intensive care unit | An average of 2 days | From admission to discharge from ICU | 
| length of stay in hospital after surgery |  | From surgery to discharge from hospital, an expected average of 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Statin, kidney function, antiinflammatory effect