Clinical trial NCT01132846: Renal Optimization Strategies Evaluation in Acute Heart Failure and Reliable Evaluation of Dyspnea in the Heart Failure Network (ROSE) Study
Official title: Renal Optimization Strategies Evaluation in Acute Heart Failure and Reliable Evaluation of Dyspnea in the Heart Failure Network ROSE Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Heart Failure
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2010-05-28
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Acute heart failure (AHF) is the most common cause of hospital admission in patients over age 65, accounting for 1,000,000 admissions, over 6 million hospital days, and $12 billion in costs annually. The prognosis of patients admitted with AHF is dismal, with a 20-30% readmission rate and a 20-30% mortality rate within six months after admission. Recent studies have established the prognostic importance of renal function in patients with heart failure. In patients who are hospitalized with decompensated congestive heart failure, worsening renal function is also associated with worse outcome, Various studies have estimated that 25-30% of patients hospitalized for decompensated CHF have worsening of renal function leading to prolonged hospitalization, increased morbidity and mortality. Although there are no FDA approved renal adjuvant therapies for AHF, several novel adjuvant therapies for use in AHF are being investigated in randomized clinical trials. Additionally, there are currently available strategies, with the potential for improving renal function in AHF such as low dose dopamine and low dose nesiritide. However, these strategies have not been investigated.

Participation in this study will last 6 months. All potential participants will undergo initial screening, which wil include a medical history, physical exam, blood draws, measurements of fluid intake and output, and questionnaires. The same evaluations and procedures will be repeated at various points during the study. Eligible participants will be randomly assigned to receive low dose nesiritide or placebo with optimal diuretic dosing or low dose dopamine or placebo with optimal diuretic dosing.

Follow-up assessments will occur at Baseline, 24 hours, 48 hours, 72 hours, day 7 or discharge, day 60 and 6 months. Follow-up assessments will include medical history, physical exam, blood draws, measurements of fluid intake and output, questionnaires and questions about medications and changes in health.

The RED ROSE substudy involves a subset of ROSE patients in looking at the dyspnea assessment. The dyspnea visual analog scale (dyspnea VAS) has been suggested to be superior to other ordinal (Likert) scales in assessment of dyspnea in acute heart failure syndromes (AHFS)1. However, there is no standardization of conditions (oxygen supplementation, position, activity) at the time of VAS assessment and thus, it may not optimally reflect the variability in dyspnea severity in AHFS patients. This insensitivity to variability at baseline and subsequent assessment may limit the ability to reflect variation in response over time and with alternate treatment strategies. A standardized and sequentially provocative assessment of dyspnea (provocative dyspnea severity score, pDSS) may better reflect variation in dyspnea severity and variation in response over time and with alternate treatment strategies. Substudy subjects will be asked to complete a provocative dyspnea assessment at baseline, 24, 48 and 72 hours. The subjects will be asked to complete a 6 minute walk assessment at the 72 hour visit.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Clinical evidence of digoxin toxicity
* Need for mechanical hemodynamic support
* Sepsis
* Terminal illness (other than HF) with expected survival of less than 1 year
* Previous adverse reaction to the study drugs
* Use of IV iodinated radiocontrast material in last 72 hours or planned during hospitalization
* Enrollment or planned enrollment in another randomized clinical trial during this hospitalization
* Inability to comply with planned study procedures
* Pregnancy or nursing mothers

Primary outcomes:
measure: Change in Cystatin C
timeFrame: Randomization to 72 hours
measure: Change in Dyspnea Assessment (RED-ROSE Substudy)
timeFrame: Baseline to 72 hours
measure: Decongestive Changes- RED-ROSE
timeFrame: Baseline to 72 hours
measure: Cumulative Urinary Volume
timeFrame: Randomization to 72 hours
Secondary outcomes:
measure: Change in Weight
timeFrame: randomization to 72 hours
measure: Worst Reported Symptom Changes-RED-ROSE
timeFrame: Change from Baseline to 72 hours
measure: Change in Clinical Stability- RED-ROSE
timeFrame: Baseline to 60 days
measure: Change in Serum Creatinine
timeFrame: randomization to 72 hours
measure: Dyspnea Visual Analog Scale Area Under the Curve
timeFrame: randomization to 72 hours
measure: Change in Heart Failure Status
timeFrame: randomization to 72 hours
measure: Change in Treatment Response
timeFrame: randomization to 72 hours
measure: Cumulative Urinary Sodium Excretion
timeFrame: Randomization to 72 hours
measure: Change in Blood Urea Nitrogen (BUN)/ Serum Cystatin C Ratio
timeFrame: Randomization to 72 hours
measure: Development of Cardio-renal Syndrome
timeFrame: Randomization to 72 hours
measure: Global Visual Analog Scale Area Under the Curve
timeFrame: Randomization to 72 hours
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: Minnesota Heart Failure Network
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Murry
country: United States
facility: University of Utah Health Sciences Center
state: Utah
city: Burlington
country: United States
facility: University of Vermont- Fletcher Allen Health Care
state: Vermont
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
Study officials:
affiliation: Duke University
name: Kerry L Lee, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Harvard University
name: Eugene Braunwald, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.