CONTRAST - CONTRAST

Description:

The goal of the CONTRAST trial was to evaluate the safety and efficacy of fenoldopam mesylate versus placebo in patients with chronic renal insufficiency undergoing invasive cardiac procedures.

Hypothesis:

Treatment with fenoldopam mesylate will be associated with a reduction in contrast-induced nephropathy versus placebo in patients with chronic renal insufficiency undergoing invasive cardiac procedures.

Study Design

Study Design:

Patients Enrolled: 315
Mean Follow Up: 30 days
Mean Patient Age: mean age 70 years
Female: 34

Patient Populations:

Age ≥18 years; creatinine clearance of <60 ml/min; and not undergoing dialysis

Exclusions:

Known severe allergy to contrast media that could not be premedicated; known allergy to fenoldopam or its infusion components such as metabisulfite or sulfites; acute renal failure or unstable renal function; systolic blood pressure <100 mm Hg; acute MI or decompensated heart or respiratory failure; contraindication to dopaminergic agents; current use of mannitol or dopamine; planned addition, discontinuation, or dose adjustment of trimethoprim, cimetidine, metoclopramide, bromocriptine, levodopa, nonsteroidal anti-inflammatory drugs, or catechol-O-methyltransferase inhibitors during the study; exposure to iodinated contrast within prior 10 days; other serious medical conditions likely to interfere with data collection or follow-up; or participation in other investigational protocols within 30 days

Primary Endpoints:

Contrast-induced nephropathy, defined as an increase of 25% or more in serum creatinine level within 96 hours postprocedure

Secondary Endpoints:

Measurements of contrast-induced nephropathy defined as two consecutive increases in serum creatinine ≥25%, and an increase in serum creatinine ≥0.5 mg/dl; duration of the index hospitalization; and 30-day death, dialysis, and rehospitalization

Drug/Procedures Used:

Patients with creatinine clearance <60 ml/min (1.00 ml/s) were randomized to fenoldopam mesylate (0.05 µg/kg/min titrated to 0.10 µg/kg/min; n=157) or placebo (n=158). Treatment was started one hour prior to angiography and continued for 12 hours.

Concomitant Medications:

After consent was obtained, a 0.45% normal saline infusion was started for 2-12 hours prior to study drug administration.

Principal Findings:

The mean creatinine clearance at baseline was 29.0 ml/min. During the procedure, the mean contrast volume used was 157 ml. Low-osmolar contrast was used in patients, with 90% of contrast nonionic.

There was no difference in the primary endpoint of contrast-induced nephropathy between the fenoldopam arm and the placebo arm (33.6% vs. 30.1%, relative risk [RR] 1.11, 95% confidence interval [CI] 0.79-1.57, p=0.61). There was also no difference in 30-day death (2.0% vs. 3.8%, p=0.50), dialysis (2.6% vs. 1.9%, p=0.72), or rehospitalization (17.6% vs. 19.9%, p=0.66). The composite of 30-day death, myocardial infarction (MI), or dialysis was higher in patients who developed contrast-induced nephropathy compared with patients who did not develop contrast-induced nephropathy (12.2% vs. 4.1%, p=0.02).

Interpretation:

Among patients with chronic renal insufficiency undergoing invasive cardiac procedures, treatment with fenoldopam mesylate was not associated with a difference in the primary endpoint of contrast-induced nephropathy compared with placebo. Results were similar when analyzed by subgroups of diabetic status, hypertension, baseline renal function, N-acetylcysteine use, or amount of hydration or contrast use.

The authors note that the negative findings in the present study and earlier negative studies of other vasodilators suggest that disturbances in intrarenal hemodynamics may not be the primary pathophysiologic link responsible for contrast-induced nephropathy.

References:

Stone GW, McCullough PA, Tumlin JA, et al., for the CONTRAST Investigators. Fenoldopam mesylate for the prevention of contrast-induced nephropathy: a randomized controlled trial. JAMA 2003;290:2284-91.

Clinical Topics: Prevention, Hypertension

Keywords: Fenoldopam, Myocardial Infarction, Kidney Failure, Chronic, Creatinine, Vasodilator Agents, Hemodynamics, Contrast Media, Renal Dialysis, Kidney Diseases, Hypertension, Diabetes Mellitus, Renal Insufficiency, Chronic


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