N-Acetylcysteine for Preventing Renal Injury After Cardiac Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00188630
Recruitment Status : Completed
First Posted : September 16, 2005
Last Update Posted : April 20, 2011
Heart and Stroke Foundation of Ontario
Information provided by:
University Health Network, Toronto

Brief Summary:
Cardiac surgery improves the survival and quality of life of people with heart disease. Nonetheless, several complications continue to adversely affect outcomes following cardiac surgery. Kidney failure is a particularly important complication that is associated with increased death and duration of hospitalization. The most severe form of postoperative kidney failure, the need for dialysis, is uncommon at present. It is however likely to increase in the future. Patients undergoing cardiac surgery are getting older with more heart failure, diabetes, high blood pressure, and pre-existing kidney disease. Given that these are risk factors for postoperative kidney injury, dialysis rates will likely increase. Although multiple therapies have been tested, none have prevented postoperative kidney failure. N-acetylcysteine (NAC) is a drug that is commonly used to treat Tylenol overdoses. Over the past 2 years, it has also been used to prevent kidney damage after exposure to IV dye. There is good evidence that NAC will reduce kidney damage after IV dye exposure. There are strong reasons to believe that NAC may also prevent postoperative kidney failure. NAC is safe. Its major side-effects are allergic reactions, but serious reactions are rare. Since dialysis is uncommon, large studies are needed to determine if NAC prevents postoperative dialysis. In this situation, a pilot study is needed to determine if such a large trial is feasible. This proposal describes a pilot study. We will determine NAC's effects on creatinine clearance, a measure of how well the kidney works. Reduced creatinine clearance is closely related to dialysis and death after cardiac surgery. This biological marker allows us to determine NAC's effects on kidney function with a reduced sample size. If NAC improves creatinine clearance, it would suggest that NAC prevents postoperative dialysis, and would justify a larger study. A pilot study will help us estimate how many patients will be willing to participate in similar studies, vital for planning a future large study. Finally, our results will estimate how well NAC will reduce dialysis rates. This is needed for calculating the sample size for future studies.The study design is a randomized, double-blinded, placebo-controlled clinical trial among patients undergoing bypass surgery or heart valve surgery at the Toronto General Hospital (Toronto, ON). We will recruit 176 people who are at increased risk for developing kidney failure after surgery. Participants will receive either NAC or sugar solution during their operation. If participants have returned home within a month of surgery, they will be contacted at home on the 30th day after surgery to determine if they had any kidney-related problems since returning home. All participants will return to the Toronto General Hospital (TGH) during the 8th week after surgery for creatinine blood test and weight.

Condition or disease Intervention/treatment Phase
Heart Disease Acute Renal Failure Drug: N-acetylcysteine Other: 5% dextrose solution Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 176 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: The PRIME (Perioperative Renal Insufficiency Management) Study: A Randomized, Double-blinded, Placebo-controlled Trial of N-acetylcysteine for Preventing Renal Injury After Cardiac Surgery.
Study Start Date : July 2003
Actual Primary Completion Date : February 2007
Actual Study Completion Date : July 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Surgery

Arm Intervention/treatment
Active Comparator: N-Acetylcysteine
IV NAC as a 100mg/kg bolus at the start of the surgical procedure (prior to the initiation of CPB), followed by a 10 mg/kg/hr infusion until 4 hours after completion of surgery
Drug: N-acetylcysteine
Placebo Comparator: Placebo
The control arm will instead receive placebo (5% dextrose solution), both as a bolus and infusion.
Other: 5% dextrose solution

Primary Outcome Measures :
  1. Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) in first 72 hours following surgery. [ Time Frame: 72 hours following surgery ]

Secondary Outcome Measures :
  1. Maximum increase in serum creatinine concentration over first 72 hours following surgery. [ Time Frame: 72 hours following surgery ]
  2. Increase in serum creatinine >= 0.5 mg/dL from baseline over first 72 hours following surgery (dichotomous outcome). [ Time Frame: 72 hours following surgery ]
  3. Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) >= 25% in first 72 hours following surgery (dichotomous outcome). [ Time Frame: 72 hours following surgery ]
  4. Percent change in calculated creatinine clearance (Cockcroft-Gault formula) at hospital discharge. [ Time Frame: hospital discharge ]
  5. Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) at 8 weeks following surgery. [ Time Frame: 8 weeks followiing surgery ]
  6. 30-day need for renal replacement therapy [ Time Frame: 30 day inclusive ]
  7. 30-day all-cause mortality [ Time Frame: 30 day follow up ]
  8. Length of stay in intensive care unit (postoperative) [ Time Frame: Duration of stay in the ICU ]
  9. Length of stay in hospital (postoperative) [ Time Frame: Until discharge form hospital ]
  10. 24-hour fluid perioperative fluid balance [ Time Frame: 24 hours ]
  11. 24-hour urine output [ Time Frame: 24 hour ]
  12. Adverse perioperative event [ Time Frame: Intra operative measure ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • CABG surgery under cardiopulmonary bypass AND/OR Valve replacement/repair surgery under cardiopulmonary bypass
  • Preoperative creatinine clearance (Cockcroft-Gault equation) <= 60 mL/min.
  • Age above 18 years
  • Informed consent

Exclusion Criteria:

  • Preoperative need for renal replacement therapy
  • Preoperative serum creatinine concentration >= 300 mmol/L
  • Prior adverse reaction to NAC with significant systemic symptoms (generalized rash, urticaria, bronchospasm, hypotension)
  • Preoperative intra-aortic balloon pump support and/or inotropes/vasopressors
  • Recent coronary angiography or intravenous dye exposure (<= 24 hours) preceding surgery
  • Planned intraoperative deep hypothermic circulatory arrest
  • Pregnancy
  • Chronic hepatitis or hepatic cirrhosis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00188630

Canada, Ontario
Toronto General Hospital, UHN
Toronto, Ontario, Canada, M5G 2C4
Sponsors and Collaborators
University Health Network, Toronto
Heart and Stroke Foundation of Ontario
Principal Investigator: William S Beattie, MD Toronto General Hospital, University Health Network

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Scott Beattie, Toronto General Hospital, University Health Network Identifier: NCT00188630     History of Changes
Other Study ID Numbers: UHN REB 03-0376-B
First Posted: September 16, 2005    Key Record Dates
Last Update Posted: April 20, 2011
Last Verified: April 2011

Keywords provided by University Health Network, Toronto:
Cardiac Surgery
Acute Renal Failure
Cardiopulmonary bypass

Additional relevant MeSH terms:
Heart Diseases
Renal Insufficiency
Acute Kidney Injury
Cardiovascular Diseases
Kidney Diseases
Urologic Diseases
Antiviral Agents
Anti-Infective Agents
Respiratory System Agents
Free Radical Scavengers
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs