N-Acetylcysteine for Preventing Renal Injury After Cardiac Surgery

This study has been completed.
Sponsor:
Collaborator:
Heart and Stroke Foundation of Ontario
Information provided by:
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT00188630
First received: September 9, 2005
Last updated: April 19, 2011
Last verified: April 2011
  Purpose

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 Intervention Phase
Heart Disease
Acute Renal Failure
Drug: N-acetylcysteine
Other: 5% dextrose solution
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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.

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) in first 72 hours following surgery. [ Time Frame: 72 hours following surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Maximum increase in serum creatinine concentration over first 72 hours following surgery. [ Time Frame: 72 hours following surgery ] [ Designated as safety issue: No ]
  • Increase in serum creatinine >= 0.5 mg/dL from baseline over first 72 hours following surgery (dichotomous outcome). [ Time Frame: 72 hours following surgery ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Percent change in calculated creatinine clearance (Cockcroft-Gault formula) at hospital discharge. [ Time Frame: hospital discharge ] [ Designated as safety issue: No ]
  • Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) at 8 weeks following surgery. [ Time Frame: 8 weeks followiing surgery ] [ Designated as safety issue: No ]
  • 30-day need for renal replacement therapy [ Time Frame: 30 day inclusive ] [ Designated as safety issue: No ]
  • 30-day all-cause mortality [ Time Frame: 30 day follow up ] [ Designated as safety issue: Yes ]
  • Length of stay in intensive care unit (postoperative) [ Time Frame: Duration of stay in the ICU ] [ Designated as safety issue: No ]
  • Length of stay in hospital (postoperative) [ Time Frame: Until discharge form hospital ] [ Designated as safety issue: No ]
  • 24-hour fluid perioperative fluid balance [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
  • 24-hour urine output [ Time Frame: 24 hour ] [ Designated as safety issue: No ]
  • Adverse perioperative event [ Time Frame: Intra operative measure ] [ Designated as safety issue: Yes ]

Enrollment: 176
Study Start Date: July 2003
Study Completion Date: July 2007
Primary Completion Date: February 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

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

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
  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: NCT00188630

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

No publications provided by University Health Network, Toronto

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Scott Beattie, Toronto General Hospital, University Health Network
ClinicalTrials.gov Identifier: NCT00188630     History of Changes
Other Study ID Numbers: UHN REB 03-0376-B, HSFO5231
Study First Received: September 9, 2005
Last Updated: April 19, 2011
Health Authority: Canada: Health Canada

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

Additional relevant MeSH terms:
Heart Diseases
Renal Insufficiency
Acute Kidney Injury
Cardiovascular Diseases
Kidney Diseases
Urologic Diseases
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 September 18, 2014