Effect of fenoldopam on use of renal replacement therapy among patients with acute kidney injury after cardiac surgery: a randomized clinical trial

JAMA. 2014 Dec 3;312(21):2244-53. doi: 10.1001/jama.2014.13573.

Abstract

Importance: No effective pharmaceutical agents have yet been identified to treat acute kidney injury after cardiac surgery.

Objective: To determine whether fenoldopam reduces the need for renal replacement therapy in critically ill cardiac surgery patients with acute kidney injury.

Design, setting, and participants: Multicenter, randomized, double-blind, placebo-controlled, parallel-group study from March 2008 to April 2013 in 19 cardiovascular intensive care units in Italy. We randomly assigned 667 patients admitted to intensive care units after cardiac surgery with early acute kidney injury (≥50% increase of serum creatinine level from baseline or oliguria for ≥6 hours) to receive fenoldopam (338 patients) or placebo (329 patients). We used a computer-generated permuted block randomization sequence for treatment allocation. All patients completed their follow-up 30 days after surgery, and data were analyzed according to the intention-to-treat principle.

Interventions: Continuous infusion of fenoldopam or placebo for up to 4 days with a starting dose of 0.1 μg/kg/min (range, 0.025-0.3 µg/kg/min).

Main outcomes and measures: The primary end point was the rate of renal replacement therapy. Secondary end points included mortality (intensive care unit and 30-day mortality) and the rate of hypotension during study drug infusion.

Results: The study was stopped for futility as recommended by the safety committee after a planned interim analysis. Sixty-nine of 338 patients (20%) allocated to the fenoldopam group and 60 of 329 patients (18%) allocated to the placebo group received renal replacement therapy (P = .47). Mortality at 30 days was 78 of 338 (23%) in the fenoldopam group and 74 of 329 (22%) in the placebo group (P = .86). Hypotension occurred in 85 (26%) patients in the fenoldopam group and in 49 (15%) patients in the placebo group (P = .001).

Conclusions and relevance: Among patients with acute kidney injury after cardiac surgery, fenoldopam infusion, compared with placebo, did not reduce the need for renal replacement therapy or risk of 30-day mortality but was associated with an increased rate of hypotension.

Trial registration: clinicaltrials.gov Identifier: NCT00621790.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury
  • Aged
  • Cardiac Surgical Procedures*
  • Creatinine
  • Critical Illness
  • Double-Blind Method
  • Female
  • Fenoldopam / adverse effects
  • Fenoldopam / therapeutic use*
  • Humans
  • Hypotension / chemically induced
  • Intensive Care Units
  • Male
  • Middle Aged
  • Postoperative Complications
  • Renal Replacement Therapy / methods*
  • United States
  • Vasodilator Agents / adverse effects
  • Vasodilator Agents / therapeutic use*

Substances

  • Vasodilator Agents
  • Creatinine
  • Fenoldopam

Associated data

  • ClinicalTrials.gov/NCT00621790