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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00332631




Registration number
NCT00332631
Ethics application status
Date submitted
31/05/2006
Date registered
1/06/2006
Date last updated
7/07/2009

Titles & IDs
Public title
High-Dose N-Acetylcysteine in Cardiac Surgery
Scientific title
High-Dose N-Acetylcysteine in Cardiac Surgery Patients at High-Risk of Postoperative Renal Dysfunction.
Secondary ID [1] 0 0
H2004/01899
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiac Surgery and Cardiopulmonary Bypass 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Absolute change in serum creatinine from baseline to peak level within the first five postoperative days.
Timepoint [1] 0 0
Secondary outcome [1] 0 0
Relative change in serum creatinine,
Timepoint [1] 0 0
Secondary outcome [2] 0 0
Highest serum creatinine,
Timepoint [2] 0 0
Secondary outcome [3] 0 0
Change in estimated glomerular filtration rate (eGFR),
Timepoint [3] 0 0
Secondary outcome [4] 0 0
Change in serum cystatin C (as a serum creatinine-independent marker of renal function during and after NAC administration (Hoffmann et al. JASN 2004),
Timepoint [4] 0 0
Secondary outcome [5] 0 0
Urinary output
Timepoint [5] 0 0
Secondary outcome [6] 0 0
Use of renal replacement therapy (RRT)
Timepoint [6] 0 0
Secondary outcome [7] 0 0
Acute renal dysfunction
Timepoint [7] 0 0
Secondary outcome [8] 0 0
Duration of ventilation,
Timepoint [8] 0 0
Secondary outcome [9] 0 0
Chest tube drainage,
Timepoint [9] 0 0
Secondary outcome [10] 0 0
Need for return to operating room,
Timepoint [10] 0 0
Secondary outcome [11] 0 0
Incidence of post-operative atrial fibrillation (AF),
Timepoint [11] 0 0
Secondary outcome [12] 0 0
Duration of stay in the intensive care unit (ICU)
Timepoint [12] 0 0
Secondary outcome [13] 0 0
Duration of stay in hospital
Timepoint [13] 0 0

Eligibility
Key inclusion criteria
* Age above 70 years
* Preexisting renal impairment (preoperative serum creatinine level >120µmol/L
* New York Heart Association class III/IV or Moderate to poor left ventricular dysfunction
* Valve surgery or complex cardiac surgery
* Redo cardiac surgery
* Insulin-dependent diabetes mellitus
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Age <18 years
* Known allergy or hypersensitivity to N-acetylcysteine
* Emergency cardiac surgery
* Planned off-pump cardiac surgery
* Enrolled in conflicting research study
* Known blood-borne infectious disease
* Chronic inflammatory disease on immunosuppression
* Chronic moderate to high dose corticosteroid therapy (>10mg/d prednisone or equivalent)
* End stage renal disease (serum creatinine >300µmol/L)
* Patients receiving pre-op IV nitrates

Study design
Purpose of the study
Prevention
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?



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
1/08/2004
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Austin Hospital - 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
At least 14% of patients develop kidney failure after cardiac surgery. Although this kidney failure can usually be treated effectively, a longer stay in intensive care is often required. While many patients suffer no long term ill effects after developing post-operative kidney failure, some require long term kidney dialysis. The investigators also know that patients who develop post-operative kidney failure are much more likely to die before they leave hospital.

Why some people develop kidney failure after cardiac surgery is not known. However, doctors suspect that the process of cardiopulmonary bypass (where the functions of the heart and lungs are taken over by a machine during the operation, to allow the surgeon to operate) overactivates some of the same mechanisms the body uses to defend itself against severe infection. Many of the cell changes by which severe infection causes kidney failure also occur after cardiopulmonary bypass. One of the main overactive defence mechanisms is the release of highly toxic compounds derived from oxygen - a process called 'oxidative stress'.

Another well-known cause of oxidative stress is paracetamol (Panadol) overdose. In large doses the oxidative stress caused by paracetamol damages cells in the liver, where it is digested, and the kidney. N-acetylcysteine is a drug in common use for the treatment of paracetamol overdose. Patients who would otherwise die of liver failure are routinely saved by N-acetylcysteine, which acts as a strong anti-oxidant.

The investigators believe that N-acetylcysteine might similarly reduce the oxidative stress which occurs during cardiac surgery, and so prevent or decrease the kidney failure which occurs in many patients. The investigators hope to give N-acetylcysteine (in similar doses to those used safely for paracetamol poisoning) to patients during, and for a day after cardiac surgery, and compare the effects with patients who have not had N-acetylcysteine. The drug, or a 5% glucose placebo, will be given through the drip which is present in all cardiac surgery patients. Whether a particular patient receives the drug or placebo will be decided at random, and neither the patient nor the investigators will know which has been given. The investigators will measure kidney function before and after the operation using the standard tests which are performed for the purposes of clinical care of every patient. Also, the investigators will do an extra test involving the collection of urine (from the urinary catheter every patient has after cardiac surgery), which provides an even better measure of kidney function. This is a potential benefit to the patient, as while this test is not routinely performed, the results will be available to the doctors in the intensive care unit. The investigators will also take four 20ml samples of blood, spaced before, during, and after the operation, from the arterial catheter routinely inserted in every patient. This is an insignificant amount of blood compared to that taken for other tests, and would have no adverse effects. This blood would be used to measure oxidative stress, and also some of the proteins inside the blood cells which are responsible for creating the toxic oxygen compounds. In this way the investigators will discover not only the effect of N-acetylcysteine, but the mechanism of that effect.

N-acetylcysteine is routinely used to treat paracetamol overdose with few side effects. An itchy skin rash is the only common side effect. Sometimes patients develop nausea and vomiting, but the treatment for this is usually very effective, and the drug will be stopped if it occurs. Rarely, as with all drugs, allergic reactions have been reported, but there are no other reported adverse effects.

There will be no extra risk to a patient who participates in the study, and no discomfort other than that normally associated with cardiac surgery. The itchy rash which occasionally develops with N-acetylcysteine would occur under anaesthetic, and would almost certainly be gone by the time the patient wakes up.

Informed consent will be obtained from the patient prior to the operation by one of the investigators or the ICU research nurse.
Trial website
https://clinicaltrials.gov/study/NCT00332631
Trial related presentations / publications
Haase M, Haase-Fielitz A, Ratnaike S, Reade MC, Bagshaw SM, Morgera S, Dragun D, Bellomo R. N-Acetylcysteine does not artifactually lower plasma creatinine concentration. Nephrol Dial Transplant. 2008 May;23(5):1581-7. doi: 10.1093/ndt/gfm818. Epub 2008 Jan 17.
Public notes

Contacts
Principal investigator
Name 0 0
Rinaldo Bellomo, MD, FRACP
Address 0 0
Austin Health
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/NCT00332631