Safety and Efficiency Study of Loading Dose Atorvastatin in Cardiac Surgery

This study has been completed.
Sponsor:
Collaborator:
Cardiovascular Institute & Fuwai Hospital
Information provided by (Responsible Party):
Shan Zhou, Peking Union Medical College
ClinicalTrials.gov Identifier:
NCT01547455
First received: February 26, 2012
Last updated: July 24, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention
Acute Kidney Injury
Drug: Atorvastatin(Lipitor)
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Anti-inflammatory and Renoprotective Effect of Pretreatment Loading Dose Atorvastatin in CABG

Resource links provided by NLM:


Further study details as provided by Peking Union Medical College:

Primary Outcome Measures:
  • acute kidney injury [ Time Frame: 72 hours after surgery ] [ Designated as safety issue: No ]
    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 [ Time Frame: 48h after surgery ] [ Designated as safety issue: No ]
    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 [ Time Frame: participants will be followed for the duration of hospital stay , an expected average of 2 weeks ] [ Designated as safety issue: No ]
    proportion need renal replacement therapy in hospital

  • liver function [ Time Frame: participants will be followed for the duration of hospital stay , an expected average of 2 weeks ] [ Designated as safety issue: Yes ]
    liver dysfunction defined as transaminase>3UNL normal level

  • death [ Time Frame: 30 days after discharge from hospital ] [ Designated as safety issue: No ]
  • MACCE events [ Time Frame: 30 days after discharge from hospital ] [ Designated as safety issue: No ]
  • length of stay in intensive care unit [ Time Frame: From admission to discharge from ICU ] [ Designated as safety issue: No ]
    An average of 2 days

  • length of stay in hospital after surgery [ Time Frame: From surgery to discharge from hospital, an expected average of 7 days ] [ Designated as safety issue: No ]

Enrollment: 96
Study Start Date: April 2012
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atorvastatin
participants take 80mg Atorvastatin orally 12h before surgery with another 40mg 2h before surgery
Drug: Atorvastatin(Lipitor)
participants take 80mg Atorvastatin orally 12h before surgery with another 40mg 2h before surgery
Other Name: Lipitor
Placebo Comparator: Control
Participants randomized to Control arm take 80mg placebo 12h before surgery with another 40mg 2h before surgery
Drug: Placebo
Participants randomized to Control arm take 80mg placebo 12h before surgery with another 40mg 2h before surgery
Other Name: Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01547455

Locations
China, Beijing
Cardiovascular Institute&Fuwai Hospital
Beijing, Beijing, China, 100037
Sponsors and Collaborators
Peking Union Medical College
Cardiovascular Institute & Fuwai Hospital
Investigators
Principal Investigator: Weipeng Wang, MD,PhD Cardiovascular Institute & Fuwai Hospital
  More Information

No publications provided

Responsible Party: Shan Zhou, Principal Investigator, Peking Union Medical College
ClinicalTrials.gov Identifier: NCT01547455     History of Changes
Other Study ID Numbers: 2011-1002-007
Study First Received: February 26, 2012
Last Updated: July 24, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by Peking Union Medical College:
Statin
kidney function
antiinflammatory effect

Additional relevant MeSH terms:
Acute Kidney Injury
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Atorvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014