A randomized controlled trial of intravenous N-acetylcysteine for the prevention of contrast-induced nephropathy after cardiac catheterization: Lack of effect

Webb, John G.; Pate, Gordon E.; Humphries, Karin H.; Buller, Christopher E.; Shalansky, Stephen; Al Shamari, Ali; Sutander, Anton; Williams, Tracey; Fox, Rebecca S.; Levin, Adeera

doi:10.1016/j.ahj.2004.03.041

« Previous Next »American Heart Journal
Volume 148, Issue 3 , Pages 422-429, September 2004

A randomized controlled trial of intravenous N-acetylcysteine for the prevention of contrast-induced nephropathy after cardiac catheterization: Lack of effect☆

John G. Webb, MD
- Divisions of Cardiology and Nephrology and the Pharmacy Department, St Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
- Reprint requests: John G. Webb, MD, Director of Cardiac Catheterization, St. Paul's Hospital, Room 5202A, 1081 Burrard St, Vancouver, British Columbia, Canada V6Z 1Y6.
Gordon E. Pate, MB, MSc
- Divisions of Cardiology and Nephrology and the Pharmacy Department, St Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
Karin H. Humphries, MBA, DSc
- Divisions of Cardiology and Nephrology and the Pharmacy Department, St Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
Christopher E. Buller, MD
- Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada
Stephen Shalansky, PharmD
- Divisions of Cardiology and Nephrology and the Pharmacy Department, St Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
Ali Al Shamari, MD
- Divisions of Cardiology and Nephrology and the Pharmacy Department, St Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
Anton Sutander, MD
- Divisions of Cardiology and Nephrology and the Pharmacy Department, St Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
Tracey Williams
- Divisions of Cardiology and Nephrology and the Pharmacy Department, St Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
Rebecca S. Fox, MSc
- Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada
Adeera Levin, MD
- Divisions of Cardiology and Nephrology and the Pharmacy Department, St Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada

Received 7 November 2003; accepted 30 March 2004.

Abstract

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 μmol/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.