Clinical trial NCT00188630: N-Acetylcysteine for Preventing Renal Injury After Cardiac Surgery
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heart Disease
Acute Renal Failure
Keywords: Cardiac Surgery
Acute Renal Failure
N-acetylcysteine
Cardiopulmonary bypass
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Heart and Stroke Foundation of Ontario
First posted: 2005-09-16
Enrollment: 176
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility 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

Primary outcomes:
measure: Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) in first 72 hours following surgery.
timeFrame: 72 hours following surgery
Secondary outcomes:
measure: Maximum increase in serum creatinine concentration over first 72 hours following surgery.
timeFrame: 72 hours following surgery
measure: Increase in serum creatinine >= 0.5 mg/dL from baseline over first 72 hours following surgery (dichotomous outcome).
timeFrame: 72 hours following surgery
measure: Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) >= 25% in first 72 hours following surgery (dichotomous outcome).
timeFrame: 72 hours following surgery
measure: Percent change in calculated creatinine clearance (Cockcroft-Gault formula) at hospital discharge.
timeFrame: hospital discharge
measure: Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) at 8 weeks following surgery.
timeFrame: 8 weeks followiing surgery
measure: 30-day need for renal replacement therapy
timeFrame: 30 day inclusive
measure: 30-day all-cause mortality
timeFrame: 30 day follow up
measure: Length of stay in intensive care unit (postoperative)
timeFrame: Duration of stay in the ICU
measure: Length of stay in hospital (postoperative)
timeFrame: Until discharge form hospital
measure: 24-hour fluid perioperative fluid balance
timeFrame: 24 hours
measure: 24-hour urine output
timeFrame: 24 hour
measure: Adverse perioperative event
timeFrame: Intra operative measure
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto General Hospital, UHN
state: Ontario
Study officials:
affiliation: Toronto General Hospital, University Health Network
name: William S Beattie, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1097/CCM.0b013e31819ffed4.