Low-dose Dopamine or Low-Dose Nesiritide in Acute Heart Failure With Renal Dysfunction: The ROSE Acute Heart Failure Randomized Trial

JAMA. 2013 Dec 18;310(23):2533-43. doi: 10.1001/jama.2013.282190.

Abstract

Importance: Small studies suggest that low-dose dopamine or low-dose nesiritide may enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction; however, neither strategy has been rigorously tested.

Objective: To test the 2 independent hypotheses that, compared with placebo, addition of low-dose dopamine (2 μg/kg/min) or low-dose nesiritide (0.005 μg/kg/min without bolus) to diuretic therapy will enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction.

Design, setting, and participants: Multicenter, double-blind, placebo-controlled clinical trial (Renal Optimization Strategies Evaluation [ROSE]) of 360 hospitalized patients with acute heart failure and renal dysfunction (estimated glomerular filtration rate of 15-60 mL/min/1.73 m2), randomized within 24 hours of admission. Enrollment occurred from September 2010 to March 2013 across 26 sites in North America.

Interventions: Participants were randomized in an open, 1:1 allocation ratio to the dopamine or nesiritide strategy. Within each strategy, participants were randomized in a double-blind, 2:1 ratio to active treatment or placebo. The dopamine (n = 122) and nesiritide (n = 119) groups were independently compared with the pooled placebo group (n = 119).

Main outcomes and measures: Coprimary end points included 72-hour cumulative urine volume (decongestion end point) and the change in serum cystatin C from enrollment to 72 hours (renal function end point).

Results: Compared with placebo, low-dose dopamine had no significant effect on 72-hour cumulative urine volume (dopamine, 8524 mL; 95% CI, 7917-9131 vs placebo, 8296 mL; 95% CI, 7762-8830 ; difference, 229 mL; 95% CI, -714 to 1171 mL; P = .59) or on the change in cystatin C level (dopamine, 0.12 mg/L; 95% CI, 0.06-0.18 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, 0.01; 95% CI, -0.08 to 0.10; P = .72). Similarly, low-dose nesiritide had no significant effect on 72-hour cumulative urine volume (nesiritide, 8574 mL; 95% CI, 8014-9134 vs placebo, 8296 mL; 95% CI, 7762-8830; difference, 279 mL; 95% CI, -618 to 1176 mL; P = .49) or on the change in cystatin C level (nesiritide, 0.07 mg/L; 95% CI, 0.01-0.13 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, -0.04; 95% CI, -0.13 to 0.05; P = .36). Compared with placebo, there was no effect of low-dose dopamine or nesiritide on secondary end points reflective of decongestion, renal function, or clinical outcomes.

Conclusion and relevance: In participants with acute heart failure and renal dysfunction, neither low-dose dopamine nor low-dose nesiritide enhanced decongestion or improved renal function when added to diuretic therapy.

Trial registration: clinicaltrials.gov Identifier: NCT01132846.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Disease
  • Aged
  • Aged, 80 and over
  • Cystatin C / blood
  • Diuretics / therapeutic use
  • Dopamine / administration & dosage*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glomerular Filtration Rate
  • Heart Failure / complications
  • Heart Failure / drug therapy*
  • Humans
  • Kidney / physiopathology
  • Kidney Diseases / complications
  • Kidney Diseases / drug therapy*
  • Male
  • Middle Aged
  • Natriuretic Agents / administration & dosage*
  • Natriuretic Peptide, Brain / administration & dosage*
  • Treatment Outcome
  • Urine
  • Vasodilator Agents / administration & dosage*

Substances

  • Cystatin C
  • Diuretics
  • Natriuretic Agents
  • Vasodilator Agents
  • Natriuretic Peptide, Brain
  • Dopamine

Associated data

  • ClinicalTrials.gov/NCT01132846