Cardiopulmonary-bypass and Reno-protective Effect of Atorvastatin Trial (CREAT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Rinaldo Bellomo, Austin Health
ClinicalTrials.gov Identifier:
NCT00910221
First received: May 28, 2009
Last updated: September 9, 2012
Last verified: August 2009
  Purpose

Acute kidney dysfunction is common after cardiac surgery. While many patients suffer no long-term ill effects from post-operative kidney dysfunction, some require initiation of dialysis therapy that can contribute to long-term morbidity. Further, there is evidence to suggest that those patients requiring dialysis after cardiac surgery have a higher risk of death in hospital.

The exact reasons why some patients develop acute kidney dysfunction after cardiac surgery is not well understood. However, research evidence to date has suggested that the presence of co-morbid illnesses (i.e., diabetes mellitus) and exposure to cardiopulmonary bypass (heart-lung machine used during operation when heart is stopped). Cardiopulmonary bypass, in particular, has been shown to over-activate several aspect of the body's immune system. Such over-activity can induce oxidative stress and contribute to acute kidney dysfunction.

The investigators believe that the statin drug, atorvastatin, might reduce the oxidative stress that occurs during cardiopulmonary bypass, and thus, prevent or reduce the magnitude of acute kidney dysfunction in those patients at highest risk. The investigators hope to give atorvastatin (40 mg orally) to patients immediately prior to and for 3 days after cardiac surgery, and to compare the effects on kidney function with patients who have not had atorvastatin.

Atorvastatin is the most commonly prescribed medication in Australia and is used to reduce blood cholesterol levels and decrease the risk of heart attacks and stroke. Recently, however, it has been discovered that atorvastatin may be useful for prevention of inflammation and oxidative stress in other conditions, such as following cardiac surgery with cardiopulmonary bypass.

Thus, the investigators plan to examine whether atorvastatin can prevent acute kidney dysfunction. This trial as planned is a pilot study. If atorvastatin shows promising evidence of reduction in acute kidney dysfunction, further studies on a larger scale would be required to justify its general use.

The investigators plan to determine whether atorvastatin, a statin drug, possesses kidney protective effects in patients at risk for perioperative acute kidney dysfunction after cardiac surgery and exposure to cardiopulmonary bypass.

This is a pilot, randomized, blinded, placebo-controlled trial.

The investigators plan to administer atorvastatin (40 mg orally) or placebo to patients immediately prior to and for 3 days after cardiac surgery. The atorvastatin/placebo will be given orally either by orogastric tube after induction of anaesthesia or swallowed by the patients.

Whether a particular patient receives the atorvastatin or placebo will be decided at random, and neither the patient nor the investigators will be aware of the allocated treatment.

The investigators plan to measure kidney function before and after cardiac surgery using the standard blood tests. The investigators also plan to measure markers of inflammation and oxidative stress in the blood. This may give insight into the mechanisms whereby atorvastatin exerts its effects. The investigators will also take four 20 ml samples of blood, spaced before, and after the operation, from the arterial catheter routinely inserted in every patient undergoing cardiac surgery.

The investigators believe that there will be no significant additional risk to a patient who participates in the study, and no discomfort other than that normally associated with cardiac surgery. Informed consent will be obtained from the patient prior to the operation by one of the investigators or the ICU research nurse. The clinical care of a patient who does not consent for any reason will not be affected.


Condition Intervention Phase
Acute Kidney Dysfunction
Drug: Atorvastatin
Drug: Placebo
Phase 2
Phase 3

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: Treatment
Official Title: A Phase II Randomised, Double-blind, Placebo-controlled Study of the Effect of Atorvastatin on Postoperative Renal Function in Patients Undergoing Elective Cardiopulmonary Bypass.

Resource links provided by NLM:


Further study details as provided by Austin Health:

Primary Outcome Measures:
  • Change in serum creatinine from baseline to peak level [ Time Frame: within first two-seven postoperative days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients developing an increase in serum creatinine > 25% or >44µmicromol/L from baseline to peak level [ Time Frame: within first two-seven postoperative days ] [ Designated as safety issue: No ]
  • Proportion of patients developing any of the RIFLE criteria: R, I or F [ Time Frame: within first seven postoperative days ] [ Designated as safety issue: No ]
  • Proportion of patients developing any of the AKI stages: 1, 2 or 3 (using network definition) [ Time Frame: within first seven postoperative days ] [ Designated as safety issue: No ]
  • Change in NGAL from baseline to peak [ Time Frame: within first 24 postoperatively ] [ Designated as safety issue: No ]
  • Requirement of renal replacement therapy [ Time Frame: within hospital stay ] [ Designated as safety issue: No ]
  • Length of stay in Intensive care [ Time Frame: from admission to discharge from Intensive care ] [ Designated as safety issue: No ]
  • Length of stay in Hospital [ Time Frame: from admission to discharge from hospital ] [ Designated as safety issue: No ]
  • Hospital-Mortality [ Time Frame: during hospital stay ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: March 2008
Study Completion Date: September 2011
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 Drug: Atorvastatin
Atorvastatin tablet
Placebo Comparator: 2 Drug: Placebo
Placebo tablet

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Cardiac surgical patients in whom the use of cardiopulmonary bypass was planned
  • Written informed consent of patient
  • Age > 18 years
  • And having at least one ore more of the following risk factors for postoperative AKI:

    • Age =/> 70 years
    • Preoperative plasma creatinine >120 µmol/L, New York Heart Association class III/IV or LVEF <35%
    • Insulin dependent diabetes mellitus
    • Valve surgery (with or without coronary artery bypass graft)
    • Redo cardiac surgery

Exclusion Criteria:

  • An emergency operation is indicated (within 24 hours after hospital admission or on intra-aortic balloon pump)
  • Pregnancy is confirmed or breastfeeding is present
  • A renal allograft is present
  • Preoperative acute renal failure within 6 weeks (acute rise in serum creatinine > 50% from baseline) is present
  • Pre-operative end stage renal disease (serum creatinine > 300 µmol/L) is present
  • Chronic moderate to high dose corticosteroid therapy (>10 mg/d prednisone or equivalent) is present
  • Known Allergy to Atorvastatin
  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: NCT00910221

Locations
Australia, Victoria
Austin Health
Melbourne, Victoria, Australia, 3084
Sponsors and Collaborators
Austin Health
  More Information

No publications provided by Austin Health

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Rinaldo Bellomo, Director of ICU research, Austin Health
ClinicalTrials.gov Identifier: NCT00910221     History of Changes
Other Study ID Numbers: H2007/02810
Study First Received: May 28, 2009
Last Updated: September 9, 2012
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Austin Health:
Cardiac surgery
Cardiopulmonary bypass
Oxidative stress
Acute renal dysfunction
Atorvastatin

Additional relevant MeSH terms:
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 18, 2014