Safety and Efficiency Study of Loading Dose Atorvastatin in Cardiac Surgery

Not Applicable

Completed

• Conditions: Acute Kidney Injury
• Interventions: Drug: Atorvastatin(Lipitor); Drug: Placebo

• Registration Number: NCT01547455
• Lead Sponsor: Peking Union Medical College

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2012-02-26
• Study First Submitted QC: 2012-03-02
• Study First Posted: 2012-03-07
• Study Start: 2012-04
• Status Verified: 2013-07
• Primary Completion: 2013-07
• Study Completion: 2013-07
• Last Update Submitted: 2013-07-24
• Last Update Posted: 2013-07-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 96

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Atorvastatin	Atorvastatin(Lipitor)	participants take 80mg Atorvastatin orally 12h before surgery with another 40mg 2h before surgery
Control	Placebo	Participants randomized to Control arm take 80mg placebo 12h before surgery with another 40mg 2h before surgery

Primary Outcome Measures

Name	Time	Method
acute kidney injury	72 hours after surgery	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.

Secondary Outcome Measures

Name	Time	Method
Change of inflammatory biomarkers	48h after surgery	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
Requirement of renal replacement therapy	participants will be followed for the duration of hospital stay , an expected average of 2 weeks	proportion need renal replacement therapy in hospital
liver function	participants will be followed for the duration of hospital stay , an expected average of 2 weeks	liver dysfunction defined as transaminase\>3UNL normal level
death	30 days after discharge from hospital
MACCE events	30 days after discharge from hospital
length of stay in intensive care unit	From admission to discharge from ICU	An average of 2 days
length of stay in hospital after surgery	From surgery to discharge from hospital, an expected average of 7 days

Trial Locations

Locations (1)

Cardiovascular Institute&Fuwai Hospital; 🇨🇳 Beijing, Beijing, China