A randomized controlled trial of intravenous N-acetylcysteine for the prevention of contrast-induced nephropathy after cardiac catheterization: lack of effect.
BACKGROUND
Contrast-induced nephropathy (CIN) after cardiac catheterization is common in patients with preexisting renal dysfunction. Studies of oral acetylcysteine to prevent CIN have produced conflicting results. Intravenous N-acetylcysteine (NAC) has logistic advantages in this setting. The objective of this study was to evaluate, in a blinded, randomized, placebo-controlled fashion, whether intravenous NAC reduced CIN in the setting of cardiac catheterization in patients with preexisting renal insufficiency.


METHODS
Patients with renal dysfunction undergoing cardiac catheterization were randomly assigned to intravenous NAC 500 mg immediately before the procedure or placebo. All patients received isotonic saline (200 mL) beforehand, followed by 1.5 mL/kg per hour for 6 hours, unless contraindicated. Exclusion criteria included acute renal failure, creatinine >400 micromol/L, concurrent dialysis, unstable clinical status, and prior NAC use. Baseline creatinine was obtained immediately before the procedure and repeated 2 to 8 days later. The primary end point was the occurrence of CIN defined as a reduction in creatinine clearance from baseline of >5 mL/min (Cockcroft-Gault formula).


RESULTS
The study was terminated early because of a determination of futility by the Data Safety Monitoring Committee after enrollment of 487 patients. The median baseline creatinine clearance was 44 mL/min (interquartile range, 33, 55). Median contrast received was 120 mL (interquartile range, 80, 175). Baseline characteristics were similar in the two groups. Altogether, 98 (22.0%) subjects had the primary end point: 23.3% in the NAC group and 20.7% in the placebo arm (P =.57).


CONCLUSIONS
In this large, randomized trial, enrolling a high-risk group of patients with impaired renal function, intravenous NAC was ineffective in preventing CIN.
Webb
John G
JG
Division of Cardiology, Pharmacy Department, St Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada. webb@providencehealth.bc.ca
Pate
Gordon E
GE
Humphries
Karin H
KH
Buller
Christopher E
CE
Shalansky
Stephen
S
Al Shamari
Ali
A
Sutander
Anton
A
Williams
Tracey
T
Fox
Rebecca S
RS
Levin
Adeera
A
D000111:Acetylcysteine / Q000627:therapeutic use*; D006328:Cardiac Catheterization; D003287:Contrast Media / Q000009:adverse effects*; D017023:Coronary Angiography; D003327:Coronary Disease / Q000150:complications / Q000000981:diagnostic imaging; D003404:Creatinine / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D017211:Treatment Failure
D003287:Contrast Media; D003404:Creatinine; D000111:Acetylcysteine