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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]

H2007/02810

Universal Trial Number (UTN)

Trial acronym

CREAT

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Acute Kidney Dysfunction

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]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Change in serum creatinine from baseline to peak level

Timepoint [1]

within first two-seven postoperative days

Secondary outcome [1]

Proportion of patients developing an increase in serum creatinine > 25% or >44µmicromol/L from baseline to peak level

Timepoint [1]

within first two-seven postoperative days

Secondary outcome [2]

Proportion of patients developing any of the RIFLE criteria: R, I or F

Timepoint [2]

within first seven postoperative days

Secondary outcome [3]

Proportion of patients developing any of the AKI stages: 1, 2 or 3 (using network definition)

Timepoint [3]

within first seven postoperative days

Secondary outcome [4]

Change in NGAL from baseline to peak

Timepoint [4]

within first 24 postoperatively

Secondary outcome [5]

Requirement of renal replacement therapy

Timepoint [5]

within hospital stay

Secondary outcome [6]

Length of stay in Intensive care

Timepoint [6]

from admission to discharge from Intensive care

Secondary outcome [7]

Length of stay in Hospital

Timepoint [7]

from admission to discharge from hospital

Secondary outcome [8]

Hospital-Mortality

Timepoint [8]

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?

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]

Austin Health - Melbourne

Recruitment postcode(s) [1]

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

Address

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT00910221

Trial Review

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