Safety and Efficiency Study of Loading Dose Atorvastatin in Cardiac Surgery

Acute Kidney Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01547455
• Other study ID #: 2011-1002-007
• Status: Completed
• Phase: N/A
• First received: February 26, 2012
• Last updated: July 24, 2013
• Start date: April 2012
• Est. completion date: July 2013

Study information

• Verified date: July 2013
• Source: Peking Union Medical College
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acute Kidney Injury

Intervention

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

Locations

Country	Name	City	State
China	Cardiovascular Institute&Fuwai Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Peking Union Medical College	Chinese Academy of Medical Sciences, Fuwai Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change of inflammatory biomarkers	we plan to measure IL-6,IL-10,TNF-a 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	No
Secondary	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	No
Secondary	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	Yes
Secondary	death		30 days after discharge from hospital	No
Secondary	MACCE events		30 days after discharge from hospital	No
Secondary	length of stay in intensive care unit	An average of 2 days	From admission to discharge from ICU	No
Secondary	length of stay in hospital after surgery		From surgery to discharge from hospital, an expected average of 7 days	No