High-Dose N-Acetylcysteine in Cardiac Surgery

This study has been completed.
Sponsor:
Information provided by:
Austin Health
ClinicalTrials.gov Identifier:
NCT00332631
First received: May 31, 2006
Last updated: July 6, 2009
Last verified: July 2009
  Purpose

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.


Condition Intervention Phase
Cardiac Surgery and Cardiopulmonary Bypass
Drug: N-acetylcysteine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: High-Dose N-Acetylcysteine in Cardiac Surgery Patients at High-Risk of Postoperative Renal Dysfunction.

Resource links provided by NLM:


Further study details as provided by Austin Health:

Primary Outcome Measures:
  • Absolute change in serum creatinine from baseline to peak level within the first five postoperative days.

Secondary Outcome Measures:
  • Relative change in serum creatinine,
  • Highest serum creatinine,
  • Change in estimated glomerular filtration rate (eGFR),
  • Change in serum cystatin C (as a serum creatinine-independent marker of renal function during and after NAC administration (Hoffmann et al. JASN 2004),
  • Urinary output
  • Use of renal replacement therapy (RRT)
  • Acute renal dysfunction
  • Duration of ventilation,
  • Chest tube drainage,
  • Need for return to operating room,
  • Incidence of post-operative atrial fibrillation (AF),
  • Duration of stay in the intensive care unit (ICU)
  • Duration of stay in hospital

Estimated Enrollment: 60
Study Start Date: August 2004
Estimated Study Completion Date: March 2006
  Show Detailed Description

  Eligibility

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

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

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
  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: NCT00332631

Locations
Australia, Victoria
Austin Hospital
Melbourne, Victoria, Australia, 3084
Sponsors and Collaborators
Austin Health
Investigators
Principal Investigator: Rinaldo Bellomo, MD, FRACP Austin Health
  More Information

No publications provided by Austin Health

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00332631     History of Changes
Other Study ID Numbers: H2004/01899
Study First Received: May 31, 2006
Last Updated: July 6, 2009
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,
N-acetylcysteine

Additional relevant MeSH terms:
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on October 01, 2014