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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT01132846
First received: May 27, 2010
Last updated: August 20, 2014
Last verified: August 2014

May 27, 2010
August 20, 2014
August 2010
May 2013   (final data collection date for primary outcome measure)
  • Change in Cystatin C [ Time Frame: Randomization to 72 hours ] [ Designated as safety issue: Yes ]
    The primary Safety endpoint is change in serum cystatin C from randomization to 72 hours.
  • Change in Dyspnea Assessment (RED-ROSE Substudy) [ Time Frame: Baseline to 72 hours ] [ Designated as safety issue: No ]

    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

  • Decongestive Changes- RED-ROSE [ Time Frame: Baseline to 72 hours ] [ Designated as safety issue: No ]

    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.

  • Cumulative Urinary Volume [ Time Frame: Randomization to 72 hours ] [ Designated as safety issue: No ]
    The primary efficacy endpoint is cumulative urinary volume (UV; +/- indwelling urinary catheter) at 72 hours
Primary Endpoint [ Time Frame: Randomization to 72 hours ] [ Designated as safety issue: Yes ]
The primary Safety endpoint is change in serum cystatin C from randomization to 72 hours. The primary efficacy endpoint is cumulative urinary volume (UV; +/- indwelling urinary catheter) at 72 hours
Complete list of historical versions of study NCT01132846 on ClinicalTrials.gov Archive Site
  • Change in Weight [ Time Frame: randomization to 72 hours ] [ Designated as safety issue: No ]
    Change in weight from randomization to 72 hours. Secondary Endpoint
  • Worst Reported Symptom Changes-RED-ROSE [ Time Frame: Change from Baseline to 72 hours ] [ Designated as safety issue: No ]

    To determine whether changes in worst reported symptom (WRS) (dyspnea, body swelling or fatigue) VAS (WRS-VAS) are related to the response to decongestive therapy as assessed by change in WRS VAS.

    WRS range -100 to + 100 Higher number is better (improved)

  • Change in Clinical Stability- RED-ROSE [ Time Frame: Baseline to 60 days ] [ Designated as safety issue: No ]
    Change in clinical stability as assessed by 60 day death, re-hospitalization or unscheduled outpatient visit
  • Change in Serum Creatinine [ Time Frame: randomization to 72 hours ] [ Designated as safety issue: No ]
  • Dyspnea Visual Analog Scale Area Under the Curve [ Time Frame: randomization to 72 hours ] [ Designated as safety issue: No ]
    Range 0 to 7200 Higher is better
  • Change in Heart Failure Status [ Time Frame: randomization to 72 hours ] [ Designated as safety issue: No ]
    Persistent or worsening heart failure defined as need for rescue therapy.
  • Change in Treatment Response [ Time Frame: randomization to 72 hours ] [ Designated as safety issue: No ]

    Treatment failure including any of the following:

    • development of cardio-renal syndrome
    • worsening/persistent heart failure
    • significant hypotension requiring discontinuation of study drug
    • significant tachycardia requiring discontinuation of study drug death
  • Cumulative Urinary Sodium Excretion [ Time Frame: Randomization to 72 hours ] [ Designated as safety issue: No ]
  • Change in Blood Urea Nitrogen (BUN)/ Serum Cystatin C Ratio [ Time Frame: Randomization to 72 hours ] [ Designated as safety issue: No ]

    BUN measured in mg/dL Cystatin C measured in mg/L

    No units were used in calculated the ratio

  • Development of Cardio-renal Syndrome [ Time Frame: Randomization to 72 hours ] [ Designated as safety issue: No ]
  • Global Visual Analog Scale Area Under the Curve [ Time Frame: Randomization to 72 hours ] [ Designated as safety issue: No ]
    Range 0 to 7200 Higher is better/improved
Secondary Endpoints [ Time Frame: randomization to 72 hours ] [ Designated as safety issue: No ]
  1. Change in serum creatinine from randomization to 72 hours
  2. Cumulative urinary sodium excretio at 72 hours
  3. Patient global well being assessment by VAS over 72 hours
  4. Dyspnea assessment by VAS over 72 hours
  5. Change in weight from randomization to 72 hours
  6. Change from randomization in BUN/ serum cystatin C ration at 72 hours
  7. Development of cardio-renal syndrome during 72 hours
  8. Persistent or worsening heart failure within 72 hours
  9. Treatment failure within 72 hours
Not Provided
Not Provided
 
Renal Optimization Strategies Evaluation in Acute Heart Failure and Reliable Evaluation of Dyspnea in the Heart Failure Network (ROSE) Study
Renal Optimization Strategies Evaluation in Acute Heart Failure and Reliable Evaluation of Dyspnea in the Heart Failure Network ROSE Study

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Acute Heart Failure
  • Other: Placebo
    Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.
    Other Name: placebo
  • Drug: Nesiritide

    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.

    Other Name: nesiritide
  • Drug: Dopamine
    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.
    Other Name: dopamine
  • Active Comparator: Low dose Dopamine

    Drug: Dopamine

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

    Intervention: Drug: Dopamine
  • Placebo Comparator: Placebo
    Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization.
    Intervention: Other: Placebo
  • Active Comparator: Low Dose Nesiritide
    Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial.
    Intervention: Drug: Nesiritide

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
360
June 2013
May 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01132846
Pro00024136, U01HL084904, Pro00029908, Pro00023578
Yes
Duke University
Duke University
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Kerry L Lee, PhD Duke University
Study Chair: Eugene Braunwald, MD Harvard University
Duke University
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP