N-Acetylcysteine for Preventing Renal Injury After Cardiac Surgery

Heart Disease Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00188630
• Other study ID #: UHN REB 03-0376-B
• Secondary ID: HSFO5231
• Status: Completed
• Phase: Phase 3
• First received: September 9, 2005
• Last updated: April 19, 2011
• Start date: July 2003
• Est. completion date: July 2007

Study information

• Verified date: April 2011
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 176
• Est. completion date: July 2007
• Est. primary completion date: February 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acute Kidney Injury
• Acute Renal Failure
• Heart Disease
• Renal Insufficiency

Intervention

Drug:
• N-acetylcysteine

Other:
• 5% dextrose solution

Locations

Country	Name	City	State
Canada	Toronto General Hospital, UHN	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	Heart and Stroke Foundation of Ontario

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) in first 72 hours following surgery.		72 hours following surgery	No
Secondary	Maximum increase in serum creatinine concentration over first 72 hours following surgery.		72 hours following surgery	No
Secondary	Increase in serum creatinine >= 0.5 mg/dL from baseline over first 72 hours following surgery (dichotomous outcome).		72 hours following surgery	No
Secondary	Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) >= 25% in first 72 hours following surgery (dichotomous outcome).		72 hours following surgery	No
Secondary	Percent change in calculated creatinine clearance (Cockcroft-Gault formula) at hospital discharge.		hospital discharge	No
Secondary	Maximum percent decline in calculated creatinine clearance (Cockcroft-Gault formula) at 8 weeks following surgery.		8 weeks followiing surgery	No
Secondary	30-day need for renal replacement therapy		30 day inclusive	No
Secondary	30-day all-cause mortality		30 day follow up	Yes
Secondary	Length of stay in intensive care unit (postoperative)		Duration of stay in the ICU	No
Secondary	Length of stay in hospital (postoperative)		Until discharge form hospital	No
Secondary	24-hour fluid perioperative fluid balance		24 hours	No
Secondary	24-hour urine output		24 hour	No
Secondary	Adverse perioperative event		Intra operative measure	Yes