Renal Optimization Strategies Evaluation in Acute Heart Failure and Reliable Evaluation of Dyspnea in the Heart Failure Network (ROSE) Study (ROSE/RED ROSE)
|Acute Heart Failure||Other: Placebo Drug: Nesiritide Drug: Dopamine||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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|
- Change in Cystatin C [ Time Frame: Randomization to 72 hours ]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 ]
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 ]
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 ]The primary efficacy endpoint is cumulative urinary volume (UV; +/- indwelling urinary catheter) at 72 hours
- Change in Weight [ Time Frame: randomization to 72 hours ]Change in weight from randomization to 72 hours. Secondary Endpoint
- Worst Reported Symptom Changes-RED-ROSE [ Time Frame: Change from Baseline to 72 hours ]
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 ]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 ]
- Dyspnea Visual Analog Scale Area Under the Curve [ Time Frame: randomization to 72 hours ]Range 0 to 7200 Higher is better
- Change in Heart Failure Status [ Time Frame: randomization to 72 hours ]Persistent or worsening heart failure defined as need for rescue therapy.
- Change in Treatment Response [ Time Frame: randomization to 72 hours ]
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 ]
- Change in Blood Urea Nitrogen (BUN)/ Serum Cystatin C Ratio [ Time Frame: Randomization to 72 hours ]
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 ]
- Global Visual Analog Scale Area Under the Curve [ Time Frame: Randomization to 72 hours ]Range 0 to 7200 Higher is better/improved
|Study Start Date:||August 2010|
|Study Completion Date:||June 2013|
|Primary Completion Date:||May 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.
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.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01132846
|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|