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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00910221




Registration number
NCT00910221
Ethics application status
Date submitted
28/05/2009
Date registered
29/05/2009
Date last updated
11/09/2012

Titles & IDs
Public title
Cardiopulmonary-bypass and Reno-protective Effect of Atorvastatin Trial
Scientific 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.
Secondary ID [1] 0 0
H2007/02810
Universal Trial Number (UTN)
Trial acronym
CREAT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Kidney Dysfunction 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atorvastatin
Treatment: Drugs - Placebo

Active comparator: 1 -

Placebo comparator: 2 -


Treatment: Drugs: Atorvastatin
Atorvastatin tablet

Treatment: Drugs: Placebo
Placebo tablet
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in serum creatinine from baseline to peak level
Timepoint [1] 0 0
within first two-seven postoperative days
Secondary outcome [1] 0 0
Proportion of patients developing an increase in serum creatinine > 25% or >44µmicromol/L from baseline to peak level
Timepoint [1] 0 0
within first two-seven postoperative days
Secondary outcome [2] 0 0
Proportion of patients developing any of the RIFLE criteria: R, I or F
Timepoint [2] 0 0
within first seven postoperative days
Secondary outcome [3] 0 0
Proportion of patients developing any of the AKI stages: 1, 2 or 3 (using network definition)
Timepoint [3] 0 0
within first seven postoperative days
Secondary outcome [4] 0 0
Change in NGAL from baseline to peak
Timepoint [4] 0 0
within first 24 postoperatively
Secondary outcome [5] 0 0
Requirement of renal replacement therapy
Timepoint [5] 0 0
within hospital stay
Secondary outcome [6] 0 0
Length of stay in Intensive care
Timepoint [6] 0 0
from admission to discharge from Intensive care
Secondary outcome [7] 0 0
Length of stay in Hospital
Timepoint [7] 0 0
from admission to discharge from hospital
Secondary outcome [8] 0 0
Hospital-Mortality
Timepoint [8] 0 0
during hospital stay

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2011
Sample size
Target
Accrual to date
Final
100
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Austin Health - Melbourne
Recruitment postcode(s) [1] 0 0
3084 - Melbourne

Funding & Sponsors
Primary sponsor type
Government body
Name
Austin Health
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00910221
Trial related presentations / publications
Prowle JR, Calzavacca P, Licari E, Ligabo EV, Echeverri JE, Haase M, Haase-Fielitz A, Bagshaw SM, Devarajan P, Bellomo R. Pilot double-blind, randomized controlled trial of short-term atorvastatin for prevention of acute kidney injury after cardiac surgery. Nephrology (Carlton). 2012 Mar;17(3):215-24. doi: 10.1111/j.1440-1797.2011.01546.x.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00910221