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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

September 9, 2005
April 19, 2011
July 2003
February 2007   (final data collection date for primary outcome measure)
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 ]
Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) in first 72 hours following surgery.
Complete list of historical versions of study NCT00188630 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Maximum increase in serum creatinine concentration over first 72 hours following surgery.
  • Increase in serum creatinine >= 0.5 mg/dL from baseline over first 72 hours following surgery (dichotomous outcome).
  • Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) >= 25% in first 72 hours following surgery (dichotomous outcome).
  • Percent change in calculated creatinine clearance (Cockcroft-Gault formula) at hospital discharge.
  • Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) at 8 weeks following surgery.
  • 30-day need for renal replacement therapy
  • 30-day all-cause mortality
  • Length of stay in intensive care unit (postoperative)
  • Length of stay in hospital (postoperative)
  • 24-hour fluid perioperative fluid balance
  • 24-hour urine output
  • Adverse perioperative event
Not Provided
Not Provided
 
N-Acetylcysteine for Preventing Renal Injury After Cardiac Surgery
The PRIME (Perioperative Renal Insufficiency Management) Study: A Randomized, Double-blinded, Placebo-controlled Trial of N-acetylcysteine for Preventing Renal Injury After Cardiac Surgery.

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • Heart Disease
  • Acute Renal Failure
  • Drug: N-acetylcysteine
  • Other: 5% dextrose solution
  • 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
    Intervention: Drug: N-acetylcysteine
  • Placebo Comparator: Placebo
    The control arm will instead receive placebo (5% dextrose solution), both as a bolus and infusion.
    Intervention: Other: 5% dextrose solution
Wijeysundera DN, Karkouti K, Rao V, Granton JT, Chan CT, Raban R, Carroll J, Poonawala H, Beattie WS. N-acetylcysteine is associated with increased blood loss and blood product utilization during cardiac surgery. Crit Care Med. 2009 Jun;37(6):1929-34.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
176
July 2007
February 2007   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00188630
UHN REB 03-0376-B, HSFO5231
Not Provided
Scott Beattie, Toronto General Hospital, University Health Network
University Health Network, Toronto
Heart and Stroke Foundation of Ontario
Principal Investigator: William S Beattie, MD Toronto General Hospital, University Health Network
University Health Network, Toronto
April 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP