As a kid growing up in the San Francisco ACT brought to mind guys in tights running around and projecting their voices at the American Conservatory Theater. Now I've got to adjust my association with the acronym with the recent publication in Circulation of the Acetylcysteine for Contrast-Induced Nephropathy Trial (ACT).
ACT is the largest randomized trial to date to evaluate the use of oral acetylcysteine prophylaxis in patients at risk for contrast induced nephropathy (CIN). In this multicenter trial, 2803 patients at risk for CIN undergoing an intravascular angiographic procedure were randomized to either acetylcysteine or placebo. Roughly 35% of patients in each group had eGFRs between 30-60 ml/min by MDRD and about 5% in each group had an eGFR of less than 30 ml/min.
The acetylcysteine group received 1200 mg of oral acetylcysteine q12 hours before and after the contrast load. The use of normal saline at a rate of 1 mL/kg per hour, from 6 to 12 hours before to 6 to 12 hours after angiography, was strongly recommended but changes in the total volume or speed of administration were permitted. In the end, 94% of patients received normal saline in both the treatment and placebo groups at some dose with 47% in both groups receiving exactly the recommended dose.
There was no difference between the treatment and placebo arms in terms of the primary outcome of CIN (defined as a 25% elevation of serum creatinine above baseline between 48 and 96 hours after angiography) or the secondary composite outcome of need for dialysis or death in the intention to treat analysis. Approximately 13% of patients in each group experienced CIN with 2% and 0.3% experiencing death or need for dialysis respectively.
This looks to be the end of the acetylcysteine in CIN argument. It's hard to imagine a larger or more well performed study. There was no hint in the subgoups that patients with more severe chronic kidney disease or diabetic nephropathy might benefit. This is clear evidence that we should drop acetylcysteine from the CIN prophylaxis tool kit and focus our efforts elsewhere.
So, the argument is not over. As noted in the commentary, the ACT results are limited by the low resolution of the description of the fluid strategies between groups leaving the bias door open a crack. The issue of generalizability is also raised in patients with advanced chronic kidney disease (and other high risk groups) given their relatively low numbers in the study. Although the ACT subgroup analyses give no hint that NAC might be of benefit in these groups the hypothesis of benefit for them remains to be adequately tested.