Renal Optimization Strategies Evaluation in Acute Heart Failure and Reliable Evaluation of Dyspnea in the Heart Failure Network (ROSE) Study

NCT01132846 | Completed Phase 2 Results DMC

• 4 other identifiers: Pro00024136U01HL084904Pro00029908Pro00023578
• Study Type: interventional
• Target: 360
• Locations: 2 countries
• Sites: 8

Brief Summary

The purpose of this study is to determine the benefits and safety of intravenous administration of low dose nesiritide or low dose dopamine in patients with congestive heart failure and kidney dysfunction. There is a substudy in a subset of subjects that is being used to determine whether the Provocative Dyspnea Severity Score (pDSS) is a more sensitive index of variability in clinical status than the dyspnea VAS assessed without standardization of conditions at assessments.

Conditions

Acute Heart Failure

Outcome Measures

Primary Outcomes (4)

• Change in Cystatin C

  The primary Safety endpoint is change in serum cystatin C from randomization to 72 hours.

  Randomization to 72 hours

• Change in Dyspnea Assessment (RED-ROSE Substudy)

  To determine whether the pDSS is a more sensitive index of variability in dyspnea status than the dyspnea VAS assessed without standardization of conditions at assessment as assessed by change in Dyspnea VAS. Dyspnea VAS range -100 to + 100 Larger number is better

  Baseline to 72 hours

• Decongestive Changes- RED-ROSE

  To determine whether changes in pDSS or dyspnea VAS are related to the response to decongestive therapy as evidenced by fluid volume loss Fluid volume loss is defined as cumulative urinary output minus fluid intake during the first 72 hours post randomization.

  Baseline to 72 hours

• Cumulative Urinary Volume

  The primary efficacy endpoint is cumulative urinary volume (UV; +/- indwelling urinary catheter) at 72 hours

  Randomization to 72 hours

Secondary Outcomes (11)

• Change in Weight

  randomization to 72 hours

• Worst Reported Symptom Changes-RED-ROSE

  Change from Baseline to 72 hours

• Change in Clinical Stability- RED-ROSE

  Baseline to 60 days

• Change in Serum Creatinine

  randomization to 72 hours

• Dyspnea Visual Analog Scale Area Under the Curve

  randomization to 72 hours

Study Arms (3)

Low dose Dopamine

ACTIVE COMPARATOR

Drug: Dopamine Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study

Drug: Dopamine

Placebo

PLACEBO COMPARATOR

Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization.

Other: Placebo

Low Dose Nesiritide

ACTIVE COMPARATOR

Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial.

Drug: Nesiritide

Interventions

Placebo OTHER

Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.

Placebo

Nesiritide DRUG

Active Comparator: Low Dose Nesiritide Participants randomized to the low dose nesiritide arm will receive nesiritide of 0.005 ug/kg/min or placebo during the first 72 hours in the trial.

Low Dose Nesiritide

Dopamine DRUG

Participants randomized to the low dose dopamine arm will receive dopamine of 2ug/kg/min or placebo during the first 72 hours in the trial.

Low dose Dopamine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A diagnosis of heart failure as defined by the presence of at least 1 symptom (dyspnea, orthopnea, or edema) AND 1 sign (rales on auscultation, peripheral edema, ascites, pulmonary vascular congestion on chest radiography)
• Prior clinical diagnosis of heart failure Must be identified within 24 hours of hospital admission (24 hour clock begins when the admission orders are placed)
• Estimated GFR of \> 15 but \< 60 mL/min/1.73m2 determined by the MDRD equation
• Male or female patient ≥18 years old
• Willingness to provide informed consent
• Ability to have a PICC or central line placed (if needed) within 12 hours of randomization and study drug infusion started
• Anticipated hospitalization of at least 72 hours

You may not qualify if:

• Received IV vasoactive treatment or ultra-filtration therapy for heart failure since initial presentation
• Anticipated need for IV vasoactive treatment or ultra-filtration for heart failure during this hospitalization
• Systolic BP \<90 mmHg
• Hemoglobin (Hgb) \< 9 g/dl
• Renal replacement therapy
• History of renal artery stenosis \> 50%
• Hemodynamically significant arrhythmias including ventricular tachycardia or defibrillator shock within 4 weeks
• Acute coronary syndrome within 4 weeks as defined by electrocardiographic (ECG) ST-segment depression or prominent T-wave inversion and/or positive biomarkers of necrosis (e.g., troponin) in the absence of ST-segment elevation and in an appropriate clinical setting (chest discomfort or anginal equivalent)
• Active myocarditis
• Hypertrophic obstructive cardiomyopathy
• Greater than moderate stenotic valvular disease
• Restrictive or constrictive cardiomyopathy
• Complex congenital heart disease
• Constrictive pericarditis
• Non-cardiac pulmonary edema

Sponsors & Collaborators

• Duke University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (8)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Minnesota Heart Failure Network

Minneapolis, Minnesota, 55415, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah Health Sciences Center

Murry, Utah, 84107, United States

Location

University of Vermont- Fletcher Allen Health Care

Burlington, Vermont, 05401, United States

Location

Montreal Heart Institute

Montreal, Quebec, H1T- 1C8, Canada

Location

Related Publications (6)

• 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 WH, Starling RC, Butler J, Deswal A, Felker GM, O'Connor CM, Bonita RE, Margulies KB, Cappola TP, Ofili EO, Mann DL, Davila-Roman VG, McNulty SE, Borlaug BA, Velazquez EJ, Lee KL, Shah MR, Hernandez AF, Braunwald E, Redfield MM; NHLBI Heart Failure Clinical Research Network. 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.

  PMID: 24247300 RESULT

• Adel FW, Rikhi A, Wan SH, Iyer SR, Chakraborty H, McNulty S, Tang WHW, Felker GM, Givertz MM, Chen HH. Annexin A1 is a Potential Novel Biomarker of Congestion in Acute Heart Failure. J Card Fail. 2020 Aug;26(8):727-732. doi: 10.1016/j.cardfail.2020.05.012. Epub 2020 May 27.

  PMID: 32473378 DERIVED

• Kelly JP, Cooper LB, Gallup D, Anstrom KJ, Chen HH, Redfield MM, O'Connor CM, Mentz RJ, Hernanadez AF, Felker GM. Implications of Using Different Definitions on Outcomes in Worsening Heart Failure. Circ Heart Fail. 2016 Aug;9(8):e003048. doi: 10.1161/CIRCHEARTFAILURE.116.003048.

  PMID: 27514750 DERIVED

• Wan SH, Stevens SR, Borlaug BA, Anstrom KJ, Deswal A, Felker GM, Givertz MM, Bart BA, Tang WH, Redfield MM, Chen HH. Differential Response to Low-Dose Dopamine or Low-Dose Nesiritide in Acute Heart Failure With Reduced or Preserved Ejection Fraction: Results From the ROSE AHF Trial (Renal Optimization Strategies Evaluation in Acute Heart Failure). Circ Heart Fail. 2016 Aug;9(8):10.1161/CIRCHEARTFAILURE.115.002593 e002593. doi: 10.1161/CIRCHEARTFAILURE.115.002593.

  PMID: 27512103 DERIVED

• de Denus S, Rouleau JL, Mann DL, Huggins GS, Cappola TP, Shah SH, Keleti J, Zada YF, Provost S, Bardhadi A, Phillips MS, Normand V, Mongrain I, Dube MP. A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: a meta-analysis of three clinical trials. Pharmacogenomics J. 2017 Mar;17(2):192-200. doi: 10.1038/tpj.2016.4. Epub 2016 Mar 1.

  PMID: 26927285 DERIVED

• Chen HH, AbouEzzeddine OF, Anstrom KJ, Givertz MM, Bart BA, Felker GM, Hernandez AF, Lee KL, Braunwald E, Redfield MM; Heart Failure Clinical Research Network. Targeting the kidney in acute heart failure: can old drugs provide new benefit? Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE AHF) trial. Circ Heart Fail. 2013 Sep 1;6(5):1087-94. doi: 10.1161/CIRCHEARTFAILURE.113.000347. No abstract available.

  PMID: 24046475 DERIVED

MeSH Terms

Interventions

Natriuretic Peptide, Brain; Dopamine

Intervention Hierarchy (Ancestors)

Natriuretic Peptides; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins; Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Kevin Anstrom
• Organization: Duke University

kevin.anstrom@dm.duke.edu

919-668-8902

Study Officials

• Kerry L Lee, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

• Eugene Braunwald, MD

  Harvard University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2010
• First Posted: May 28, 2010
• Study Start: August 1, 2010
• Primary Completion: May 1, 2013
• Study Completion: June 1, 2013
• Last Updated: August 21, 2014
• Results First Posted: August 21, 2014

Record last verified: 2014-08

Locations

US (7); CA (1)