Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial

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.

Conflict of interest statement

Author Conflict of Interest Disclosures

HH Chen: Dr. Chen

KJ Anstrom: Dr. Anstrom

MM Givertz: Dr. Givertz

LW Stevenson: Dr. Stevenson

MJ Semigran: Dr. Semigran

SR Goldsmith: Dr. Goldsmith

BA Bart: Dr. Bart

DA Bull: Dr. Bull

J Stehlik: Dr. Stehlik

MM LeWinter: Dr. LeWinter

MA Konstam: Dr. Konstam

GS Huggins: Dr. Huggins

JL Rouleau: Dr. Rouleau

E O’Meara: Dr. O’Meara

WHW Tang: Dr. Tang

RC Starling: Dr. Starling

J Butler: Dr. Butler

A Deswal: Dr. Deswal

GM Felker: Dr. Felker

CM O’Connor: Dr. O’Connor

RE Bonita: Dr. Bonita

KB Margulies: Dr. Margulies

TP Cappola: Dr. Cappola

EO Ofili: Dr. Ofili

DL Mann: Dr. Mann

VG Davila-Roman: Dr. Davila-Roman

SE McNulty: Dr. McNulty

BA Borlaug: Dr. Borlaug

EJ Velazquez: Dr. Velazquez

KL Lee: Dr. Lee

MR Shah: Dr. Shah

AF Hernandez: Dr. Hernandez

E Braunwald: Dr. Braunwald

MM Redfield: Dr. Redfield

Figures

Figure 1

ROSE CONSORT Diagram This figure displays the ROSE CONSORT diagram, from enrollment to randomization to final analysis population. Abbreviations: UV, urine volume aData on patients screened for eligibility is not available. bThe primary endpoints were analyzed using multiple imputation techniques when data were unavailable for the endpoint.

Figure 2

Dopamine Strategy Subgroup Analysis This figure displays the subgroup analysis of treatment effect on: (A) cumulative urinary volume over 72 hours; and (B) change in cystatin-C from baseline to 72 hours with low dose dopamine versus placebo. aNormalized to 1.73 m2

Figure 3

Nesiritide Strategy Subgroup Analysis This figure displays the subgroup analysis of treatment effect on: (A) cumulative urinary volume over 72 hours; and (B) change in cystatin-C from baseline to 72 hours with low dose nesiritide versus placebo. aNormalized to 1.73 m2