Renal Optimization Strategies Evaluation in Acute Heart Failure and Reliable Evaluation of Dyspnea in the Heart Failure Network (ROSE) Study (ROSE/RED ROSE)
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
|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|
- Primary Endpoint- 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.
- RED-ROSE substudy- Change in Dyspnea assessment [ 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.
- RED-ROSE Decongestive changes [ 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.
- Primary Endpoint- 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 Endpoints-Change in Weight [ Time Frame: randomization to 72 hours ] [ Designated as safety issue: No ]Change in weight from randomization to 72 hours
- RED-ROSE Worst Reported Symptom changes [ 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.
- RED-ROSE Change in clinical stability [ 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).
- Secondary Endpoint- Change in Lab values [ Time Frame: randomization to 72 hours ] [ Designated as safety issue: No ]
- Change in serum creatinine
- Cumulative urinary sodium excretion
- Change in Blood Urea Nitrogen (BUN)/ serum cystatin C ratio
- 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
|Study Start Date:||August 2010|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Active Comparator: Low dose Dopamine
Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study
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.
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.
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
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.
|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|
|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|
|Montreal Heart Institute|
|Montreal, Quebec, Canada, H1T- 1C8|
|Principal Investigator:||Kerry L Lee, PhD||Duke University|
|Study Chair:||Eugene Braunwald, MD||Harvard University|