Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction

The ROSE acute heart failure randomized trial

Horng Haur Chen, Kevin J. Anstrom, Michael M. Givertz, Lynne W. Stevenson, Marc J. Semigran, Steven R. Goldsmith, Bradley A. Bart, David A. Bull, Josef Stehlik, Martin M. LeWinter, Marvin A. Konstam, Gordon S. Huggins, Jean L. Rouleau, Eileen O'Meara, W. H Wilson Tang, Randall C. Starling, Javed Butler, Anita Deswal, G. Michael Felker, Christopher M. O'Connor & 14 others Raphael E. Bonita, Kenneth B. Margulies, Thomas P. Cappola, Elizabeth O. Ofili, Douglas L. Mann, Victor G. Dávila-Román, Steven E. McNulty, Barry A Borlaug, Eric J. Velazquez, Kerry L. Lee, Monica R. Shah, Adrian F. Hernandez, Eugene Braunwald, Margaret May Redfield

Research output: Contribution to journalArticle

249 Citations (Scopus)

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/1.73m2), 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, 0.12mg/L; 95%CI, 0.06-0.18 vs placebo, 0.11mg/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, 0.07mg/L; 95%CI, 0.01-0.13 vs placebo, 0.11mg/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

Original languageEnglish (US)
Pages (from-to)2533-2543
Number of pages11
JournalJAMA - Journal of the American Medical Association
Volume310
Issue number23
DOIs
StatePublished - 2013

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Brain Natriuretic Peptide
Dopamine
Heart Failure
Placebos
Kidney
Acute Kidney Injury
Cystatin C
Urine
Diuretics
Controlled Clinical Trials
North America
Glomerular Filtration Rate
Therapeutics
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction : The ROSE acute heart failure randomized trial. / Chen, Horng Haur; Anstrom, Kevin J.; Givertz, Michael M.; Stevenson, Lynne W.; Semigran, Marc J.; Goldsmith, Steven R.; Bart, Bradley A.; Bull, David A.; Stehlik, Josef; LeWinter, Martin M.; Konstam, Marvin A.; Huggins, Gordon S.; Rouleau, Jean L.; O'Meara, Eileen; Tang, W. H Wilson; Starling, Randall C.; Butler, Javed; Deswal, Anita; Felker, G. Michael; O'Connor, Christopher M.; Bonita, Raphael E.; Margulies, Kenneth B.; Cappola, Thomas P.; Ofili, Elizabeth O.; Mann, Douglas L.; Dávila-Román, Victor G.; McNulty, Steven E.; Borlaug, Barry A; Velazquez, Eric J.; Lee, Kerry L.; Shah, Monica R.; Hernandez, Adrian F.; Braunwald, Eugene; Redfield, Margaret May.

In: JAMA - Journal of the American Medical Association, Vol. 310, No. 23, 2013, p. 2533-2543.

Research output: Contribution to journalArticle

Chen, HH, Anstrom, KJ, Givertz, MM, Stevenson, LW, Semigran, MJ, Goldsmith, SR, Bart, BA, Bull, DA, Stehlik, J, LeWinter, MM, Konstam, MA, Huggins, GS, Rouleau, JL, O'Meara, E, Tang, WHW, Starling, RC, Butler, J, Deswal, A, Felker, GM, O'Connor, CM, Bonita, RE, Margulies, KB, Cappola, TP, Ofili, EO, Mann, DL, Dávila-Román, VG, McNulty, SE, Borlaug, BA, Velazquez, EJ, Lee, KL, Shah, MR, Hernandez, AF, Braunwald, E & Redfield, MM 2013, 'Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: The ROSE acute heart failure randomized trial', JAMA - Journal of the American Medical Association, vol. 310, no. 23, pp. 2533-2543. https://doi.org/10.1001/jama.2013.282190
Chen, Horng Haur ; Anstrom, Kevin J. ; Givertz, Michael M. ; Stevenson, Lynne W. ; Semigran, Marc J. ; Goldsmith, Steven R. ; Bart, Bradley A. ; Bull, David A. ; Stehlik, Josef ; LeWinter, Martin M. ; Konstam, Marvin A. ; Huggins, Gordon S. ; Rouleau, Jean L. ; O'Meara, Eileen ; Tang, W. H Wilson ; Starling, Randall C. ; Butler, Javed ; Deswal, Anita ; Felker, G. Michael ; O'Connor, Christopher M. ; Bonita, Raphael E. ; Margulies, Kenneth B. ; Cappola, Thomas P. ; Ofili, Elizabeth O. ; Mann, Douglas L. ; Dávila-Román, Victor G. ; McNulty, Steven E. ; Borlaug, Barry A ; Velazquez, Eric J. ; Lee, Kerry L. ; Shah, Monica R. ; Hernandez, Adrian F. ; Braunwald, Eugene ; Redfield, Margaret May. / Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction : The ROSE acute heart failure randomized trial. In: JAMA - Journal of the American Medical Association. 2013 ; Vol. 310, No. 23. pp. 2533-2543.
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title = "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/1.73m2), 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, 0.12mg/L; 95{\%}CI, 0.06-0.18 vs placebo, 0.11mg/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, 0.07mg/L; 95{\%}CI, 0.01-0.13 vs placebo, 0.11mg/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",
author = "Chen, {Horng Haur} and Anstrom, {Kevin J.} and Givertz, {Michael M.} and Stevenson, {Lynne W.} and Semigran, {Marc J.} and Goldsmith, {Steven R.} and Bart, {Bradley A.} and Bull, {David A.} and Josef Stehlik and LeWinter, {Martin M.} and Konstam, {Marvin A.} and Huggins, {Gordon S.} and Rouleau, {Jean L.} and Eileen O'Meara and Tang, {W. H Wilson} and Starling, {Randall C.} and Javed Butler and Anita Deswal and Felker, {G. Michael} and O'Connor, {Christopher M.} and Bonita, {Raphael E.} and Margulies, {Kenneth B.} and Cappola, {Thomas P.} and Ofili, {Elizabeth O.} and Mann, {Douglas L.} and D{\'a}vila-Rom{\'a}n, {Victor G.} and McNulty, {Steven E.} and Borlaug, {Barry A} and Velazquez, {Eric J.} and Lee, {Kerry L.} and Shah, {Monica R.} and Hernandez, {Adrian F.} and Eugene Braunwald and Redfield, {Margaret May}",
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TY - JOUR

T1 - Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction

T2 - The ROSE acute heart failure randomized trial

AU - Chen, Horng Haur

AU - Anstrom, Kevin J.

AU - Givertz, Michael M.

AU - Stevenson, Lynne W.

AU - Semigran, Marc J.

AU - Goldsmith, Steven R.

AU - Bart, Bradley A.

AU - Bull, David A.

AU - Stehlik, Josef

AU - LeWinter, Martin M.

AU - Konstam, Marvin A.

AU - Huggins, Gordon S.

AU - Rouleau, Jean L.

AU - O'Meara, Eileen

AU - Tang, W. H Wilson

AU - Starling, Randall C.

AU - Butler, Javed

AU - Deswal, Anita

AU - Felker, G. Michael

AU - O'Connor, Christopher M.

AU - Bonita, Raphael E.

AU - Margulies, Kenneth B.

AU - Cappola, Thomas P.

AU - Ofili, Elizabeth O.

AU - Mann, Douglas L.

AU - Dávila-Román, Victor G.

AU - McNulty, Steven E.

AU - Borlaug, Barry A

AU - Velazquez, Eric J.

AU - Lee, Kerry L.

AU - Shah, Monica R.

AU - Hernandez, Adrian F.

AU - Braunwald, Eugene

AU - Redfield, Margaret May

PY - 2013

Y1 - 2013

N2 - 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/1.73m2), 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, 0.12mg/L; 95%CI, 0.06-0.18 vs placebo, 0.11mg/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, 0.07mg/L; 95%CI, 0.01-0.13 vs placebo, 0.11mg/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

AB - 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/1.73m2), 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, 0.12mg/L; 95%CI, 0.06-0.18 vs placebo, 0.11mg/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, 0.07mg/L; 95%CI, 0.01-0.13 vs placebo, 0.11mg/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

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JF - JAMA - Journal of the American Medical Association

SN - 0002-9955

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