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: January 14, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Acute Heart Failure
Other: Placebo
Drug: Nesiritide
Drug: Dopamine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Renal Optimization Strategies Evaluation in Acute Heart Failure and Reliable Evaluation of Dyspnea in the Heart Failure Network ROSE Study

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • 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.

  • 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.

  • 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


Secondary Outcome Measures:
  • 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: 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.

  • Change in clinical stability- RED-ROSE [ Time Frame: Baseline to 72 hours ] [ Designated as safety issue: No ]
    To compare the predictive characteristics of clinical stability assessments scores (pDSS-2, dyspnea VAS, worst symptom VAS (WRS-VAS), 6MW distance and NT-proBNP) assessed at 72 hours for predicting 60-day post-discharge outcomes (combined endpoint of ED visit or re-hospitalization for HF or death) in patients hospitalized for Acute Heart Failure Syndromes (AHFS).

  • Change in Lab values [ Time Frame: randomization to 72 hours ] [ Designated as safety issue: No ]
    1. Change in serum creatinine
    2. Cumulative urinary sodium excretion
    3. Change in Blood Urea Nitrogen (BUN)/ serum cystatin C ratio
    4. Development of Cardio-renal syndrome Secondary Endpoint

  • Change in assessments [ Time Frame: randomization to 72 hours ] [ Designated as safety issue: No ]
    Change in patient global well being and Dyspnea assessment by Visual Analog scale. Secondary endpoint-

  • Change in heart failure status [ Time Frame: randomization to 72 hours ] [ Designated as safety issue: Yes ]
    Persistent or worsening heart failure defined as need for rescue therapy. Secondary Endpoint

  • Change in treatment response [ Time Frame: randomization to 72 hours ] [ Designated as safety issue: Yes ]

    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 Secondary endpoint


Enrollment: 360
Study Start Date: August 2010
Study Completion Date: June 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01132846

Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Minnesota
Minnesota Heart Failure Network
Minneapolis, Minnesota, United States, 55415
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Utah
University of Utah Health Sciences Center
Murry, Utah, United States, 84107
United States, Vermont
University of Vermont- Fletcher Allen Health Care
Burlington, Vermont, United States, 05401
Canada, Quebec
Montreal Heart Institute
Montreal, Quebec, Canada, H1T- 1C8
Sponsors and Collaborators
Duke University
Investigators
Principal Investigator: Kerry L Lee, PhD Duke University
Study Chair: Eugene Braunwald, MD Harvard University
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT01132846     History of Changes
Other Study ID Numbers: Pro00024136 and Pro00029908, U01HL084904, Pro00029908, Pro00023578
Study First Received: May 27, 2010
Last Updated: January 14, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Dopamine
Dopamine Agents
Natriuretic Peptide, Brain
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents
Natriuretic Agents

ClinicalTrials.gov processed this record on July 09, 2014