Acute Kidney Dysfunction Clinical Trial
— CREATOfficial 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.
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.
| Status | Completed |
| Enrollment | 100 |
| Est. completion date | September 2011 |
| Est. primary completion date | August 2010 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
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 |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Australia | Austin Health | Melbourne | Victoria |
| Lead Sponsor | Collaborator |
|---|---|
| Austin Health |
Australia,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Change in serum creatinine from baseline to peak level | within first two-seven postoperative days | No | |
| Secondary | Proportion of patients developing an increase in serum creatinine > 25% or >44µmicromol/L from baseline to peak level | within first two-seven postoperative days | No | |
| Secondary | Proportion of patients developing any of the RIFLE criteria: R, I or F | within first seven postoperative days | No | |
| Secondary | Proportion of patients developing any of the AKI stages: 1, 2 or 3 (using network definition) | within first seven postoperative days | No | |
| Secondary | Change in NGAL from baseline to peak | within first 24 postoperatively | No | |
| Secondary | Requirement of renal replacement therapy | within hospital stay | No | |
| Secondary | Length of stay in Intensive care | from admission to discharge from Intensive care | No | |
| Secondary | Length of stay in Hospital | from admission to discharge from hospital | No | |
| Secondary | Hospital-Mortality | during hospital stay | No |