title: Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01132846.
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Horng H
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Anstrom
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Givertz
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Lynne W
authors.initials: LW
authors.lastname: Stevenson
authors.affiliation: Massachusetts General Hospital, Boston.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Semigran
authors.affiliation: Hennepin County Medical Center, Minneapolis, Minnesota.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldsmith
authors.affiliation: Hennepin County Medical Center, Minneapolis, Minnesota.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Bart
authors.affiliation: University of Utah, Salt Lake City.
authors.forename: David A
authors.initials: DA
authors.lastname: Bull
authors.affiliation: University of Utah, Salt Lake City.
authors.forename: Josef
authors.initials: J
authors.lastname: Stehlik
authors.affiliation: University of Vermont, Burlington.
authors.forename: Martin M
authors.initials: MM
authors.lastname: LeWinter
authors.affiliation: Tufts Medical Center, Boston, Massachusetts.
authors.forename: Marvin A
authors.initials: MA
authors.lastname: Konstam
authors.affiliation: Tufts Medical Center, Boston, Massachusetts.
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Huggins
authors.affiliation: University of Montreal and Montreal Heart Institute, Montreal, Canada.
authors.forename: Jean L
authors.initials: JL
authors.lastname: Rouleau
authors.affiliation: University of Montreal and Montreal Heart Institute, Montreal, Canada.
authors.forename: Eileen
authors.initials: E
authors.lastname: O'Meara
authors.affiliation: Cleveland Clinic, Cleveland, Ohio.
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
authors.affiliation: Cleveland Clinic, Cleveland, Ohio.
authors.forename: Randall C
authors.initials: RC
authors.lastname: Starling
authors.affiliation: Emory University, Atlanta, Georgia.
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
authors.affiliation: Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, Texas.
authors.forename: Anita
authors.initials: A
authors.lastname: Deswal
authors.affiliation: Duke University Medical Center and Duke Heart Center, Durham, North Carolina.
authors.forename: G Michael
authors.initials: GM
authors.lastname: Felker
authors.affiliation: Duke University Medical Center and Duke Heart Center, Durham, North Carolina.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
authors.affiliation: Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Raphael E
authors.initials: RE
authors.lastname: Bonita
authors.affiliation: University of Pennsylvania, Philadelphia.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Margulies
authors.affiliation: University of Pennsylvania, Philadelphia.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Cappola
authors.affiliation: Morehouse School of Medicine, Atlanta, Georgia.
authors.forename: Elizabeth O
authors.initials: EO
authors.lastname: Ofili
authors.affiliation: Washington University School of Medicine, St Louis, Missouri.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Mann
authors.affiliation: Washington University School of Medicine, St Louis, Missouri.
authors.forename: Víctor G
authors.initials: VG
authors.lastname: Dávila-Román
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Steven E
authors.initials: SE
authors.lastname: McNulty
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Barry A
authors.initials: BA
authors.lastname: Borlaug
authors.affiliation: Duke University Medical Center and Duke Heart Center, Durham, North Carolina.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Velazquez
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Lee
authors.affiliation: National Heart, Lung, and Blood Institute, Bethesda, Maryland.
authors.forename: Monica R
authors.initials: MR
authors.lastname: Shah
authors.affiliation: Duke Clinical Research Institute, Durham, North Carolina.
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Hernandez
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Redfield
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D055316:Cystatin C / Q000097:blood; D004232:Diuretics / Q000627:therapeutic use; D004298:Dopamine / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D007674:Kidney Diseases / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D045283:Natriuretic Agents / Q000008:administration & dosage*; D020097:Natriuretic Peptide, Brain / Q000008:administration & dosage*; D016896:Treatment Outcome; D014556:Urine; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D055316:Cystatin C; D004232:Diuretics; D045283:Natriuretic Agents; D014665:Vasodilator Agents; D020097:Natriuretic Peptide, Brain; D004298:Dopamine