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Safety and Efficiency Study of Loading Dose Atorvastatin in Cardiac Surgery

Primary Purpose

Acute Kidney Injury

Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Atorvastatin(Lipitor)
Placebo
Sponsored by
Peking Union Medical College
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Acute Kidney Injury focused on measuring Statin, kidney function, antiinflammatory effect

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cardiovascular Institute&Fuwai Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Atorvastatin

Control

Arm Description

participants take 80mg Atorvastatin orally 12h before surgery with another 40mg 2h before surgery

Participants randomized to Control arm take 80mg placebo 12h before surgery with another 40mg 2h before surgery

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
Requirement of renal replacement therapy
proportion need renal replacement therapy in hospital
liver function
liver dysfunction defined as transaminase>3UNL normal level
death
MACCE events
length of stay in intensive care unit
An average of 2 days
length of stay in hospital after surgery

Full Information

First Posted
February 26, 2012
Last Updated
July 24, 2013
Sponsor
Peking Union Medical College
Collaborators
Chinese Academy of Medical Sciences, Fuwai Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01547455
Brief Title
Safety and Efficiency Study of Loading Dose Atorvastatin in Cardiac Surgery
Official Title
Anti-inflammatory and Renoprotective Effect of Pretreatment Loading Dose Atorvastatin in CABG
Study Type
Interventional

2. Study Status

Record Verification Date
July 2013
Overall Recruitment Status
Completed
Study Start Date
April 2012 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
July 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking Union Medical College
Collaborators
Chinese Academy of Medical Sciences, Fuwai Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Kidney Injury
Keywords
Statin, kidney function, antiinflammatory effect

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
96 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Atorvastatin
Arm Type
Experimental
Arm Description
participants take 80mg Atorvastatin orally 12h before surgery with another 40mg 2h before surgery
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Participants randomized to Control arm take 80mg placebo 12h before surgery with another 40mg 2h before surgery
Intervention Type
Drug
Intervention Name(s)
Atorvastatin(Lipitor)
Other Intervention Name(s)
Lipitor
Intervention Description
participants take 80mg Atorvastatin orally 12h before surgery with another 40mg 2h before surgery
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants randomized to Control arm take 80mg placebo 12h before surgery with another 40mg 2h before surgery
Primary Outcome Measure Information:
Title
acute kidney injury
Description
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.
Time Frame
72 hours after surgery
Secondary Outcome Measure Information:
Title
Change of inflammatory biomarkers
Description
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
Time Frame
48h after surgery
Title
Requirement of renal replacement therapy
Description
proportion need renal replacement therapy in hospital
Time Frame
participants will be followed for the duration of hospital stay , an expected average of 2 weeks
Title
liver function
Description
liver dysfunction defined as transaminase>3UNL normal level
Time Frame
participants will be followed for the duration of hospital stay , an expected average of 2 weeks
Title
death
Time Frame
30 days after discharge from hospital
Title
MACCE events
Time Frame
30 days after discharge from hospital
Title
length of stay in intensive care unit
Description
An average of 2 days
Time Frame
From admission to discharge from ICU
Title
length of stay in hospital after surgery
Time Frame
From surgery to discharge from hospital, an expected average of 7 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Weipeng Wang, MD,PhD
Organizational Affiliation
Chinese Academy of Medical Sciences, Fuwai Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cardiovascular Institute&Fuwai Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100037
Country
China

12. IPD Sharing Statement

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Safety and Efficiency Study of Loading Dose Atorvastatin in Cardiac Surgery

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