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

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01132846
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 360
• Locations: 8
• Arms: 3
• Duration (Months): 34
• Patients Per Site: 45
• Patients Per Site Per Month: 1.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Heart Failure	Other: Placebo; Drug: Nesiritide; Drug: Dopamine	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 360 participants
• 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
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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.
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.
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.

Outcome Measures

Primary Outcome Measures

1. Change in Cystatin C [Randomization to 72 hours]

   The primary Safety endpoint is change in serum cystatin C from randomization to 72 hours.

2. Change in Dyspnea Assessment (RED-ROSE Substudy) [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

3. Decongestive Changes- RED-ROSE [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.

4. Cumulative Urinary Volume [Randomization to 72 hours]

   The primary efficacy endpoint is cumulative urinary volume (UV; +/- indwelling urinary catheter) at 72 hours

Secondary Outcome Measures

1. Change in Weight [randomization to 72 hours]

   Change in weight from randomization to 72 hours. Secondary Endpoint

2. Worst Reported Symptom Changes-RED-ROSE [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)

3. Change in Clinical Stability- RED-ROSE [Baseline to 60 days]

   Change in clinical stability as assessed by 60 day death, re-hospitalization or unscheduled outpatient visit

4. Change in Serum Creatinine [randomization to 72 hours]

5. Dyspnea Visual Analog Scale Area Under the Curve [randomization to 72 hours]

   Range 0 to 7200 Higher is better

6. Change in Heart Failure Status [randomization to 72 hours]

   Persistent or worsening heart failure defined as need for rescue therapy.

7. Change in Treatment Response [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

8. Cumulative Urinary Sodium Excretion [Randomization to 72 hours]

9. Change in Blood Urea Nitrogen (BUN)/ Serum Cystatin C Ratio [Randomization to 72 hours]

   BUN measured in mg/dL Cystatin C measured in mg/L No units were used in calculated the ratio

10. Development of Cardio-renal Syndrome [Randomization to 72 hours]

11. Global Visual Analog Scale Area Under the Curve [Randomization to 72 hours]

    Range 0 to 7200 Higher is better/improved

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
2	Minnesota Heart Failure Network	Minneapolis	Minnesota	United States	55415
3	Mayo Clinic	Rochester	Minnesota	United States	55905
4	Duke University Medical Center	Durham	North Carolina	United States	27705
5	Baylor College of Medicine	Houston	Texas	United States	77030
6	University of Utah Health Sciences Center	Murry	Utah	United States	84107
7	University of Vermont- Fletcher Allen Health Care	Burlington	Vermont	United States	05401
8	Montreal Heart Institute	Montreal	Quebec	Canada	H1T- 1C8

Sponsors and Collaborators

• Duke University
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Kerry L Lee, PhD, Duke University
• Study Chair: Eugene Braunwald, MD, Harvard University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT01132846
• Other Study ID Numbers: Pro00024136; U01HL084904; Pro00029908; Pro00023578
• First Posted: May 28, 2010
• Last Update Posted: Aug 21, 2014
• Last Verified: Aug 1, 2014

• Additional relevant MeSH terms: Dyspnea; Heart Failure; Dopamine; Natriuretic Peptide, Brain

Study Results

Participant Flow

Arm/Group Title	Low Dose Dopamine	Placebo	Low Dose Nesiritide
Arm/Group Description	Drug: Dopamine Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study 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.	Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization. Placebo: Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.	Drug: Nesiritide Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial. 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.
Period Title: Overall Study
STARTED	122	119	119
COMPLETED	106	101	108
NOT COMPLETED	16	18	11

Baseline Characteristics

Arm/Group Title	Low Dose Dopamine	Placebo	Low Dose Nesiritide	Total
Arm/Group Description	Drug: Dopamine Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study 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.	Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization. Placebo: Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.	Drug: Nesiritide Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial. 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.	Total of all reporting groups
Overall Participants	122	119	119	360
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.0 (11.1)	69.3 (12.6)	68.3 (13.0)	69.6 (12.3)
Sex: Female, Male (Count of Participants)
Female	38 31.1%	30 25.2%	28 23.5%	96 26.7%
Male	84 68.9%	89 74.8%	91 76.5%	264 73.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	3 2.5%	1 0.8%	3 2.5%	7 1.9%
Asian	1 0.8%	1 0.8%	1 0.8%	3 0.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	27 22.1%	23 19.3%	24 20.2%	74 20.6%
White	90 73.8%	91 76.5%	91 76.5%	272 75.6%
More than one race	1 0.8%	1 0.8%	0 0%	2 0.6%
Unknown or Not Reported	0 0%	2 1.7%	0 0%	2 0.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 4.9%	5 4.2%	3 2.5%	14 3.9%
Not Hispanic or Latino	116 95.1%	112 94.1%	116 97.5%	344 95.6%
Unknown or Not Reported	0 0%	2 1.7%	0 0%	2 0.6%

Outcome Measures

1. Primary Outcome

Title	Change in Cystatin C
Description	The primary Safety endpoint is change in serum cystatin C from randomization to 72 hours.
Time Frame	Randomization to 72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Dose Dopamine	Placebo	Low Dose Nesiritide
Arm/Group Description	Drug: Dopamine Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study 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.	Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization. Placebo: Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.	Drug: Nesiritide Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial. 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.
Measure Participants	122	119	119
Mean (Standard Deviation) [mg/L]	.12 (.32)	.11 (.27)	.07 (.34)

2. Primary Outcome

Title	Change in Dyspnea Assessment (RED-ROSE Substudy)
Description	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
Time Frame	Baseline to 72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Dose Dopamine	Placebo	Low Dose Nesiritide
Arm/Group Description	Drug: Dopamine Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study 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.	Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization. Placebo: Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.	Drug: Nesiritide Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial. 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.
Measure Participants	70	70	73
Mean (Standard Deviation) [units on a scale]	16.1 (30.7)	16.2 (22.3)	16.8 (24.2)

3. Primary Outcome

Title	Decongestive Changes- RED-ROSE
Description	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.
Time Frame	Baseline to 72 hours

Outcome Measure Data

Analysis Population Description

RED-ROSE is a substudy of the overall ROSE study. Only consented and enrolled RED-ROSE subjects participated.

Arm/Group Title	Low Dose Dopamine	Placebo	Low Dose Nesiritide
Arm/Group Description	Drug: Dopamine Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study 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.	Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization. Placebo: Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.	Drug: Nesiritide Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial. 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.
Measure Participants	74	72	72
Mean (Standard Deviation) [mL]	4526.0 (3191.9)	4659.9 (2862.5)	5177.2 (2830.5)

4. Primary Outcome

Title	Cumulative Urinary Volume
Description	The primary efficacy endpoint is cumulative urinary volume (UV; +/- indwelling urinary catheter) at 72 hours
Time Frame	Randomization to 72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Dose Dopamine	Placebo	Low Dose Nesiritide
Arm/Group Description	Drug: Dopamine Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study 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.	Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization. Placebo: Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.	Drug: Nesiritide Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial. 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.
Measure Participants	122	119	119
Mean (Standard Deviation) [mL]	8524 (3418)	8296 (2973)	8574 (3115)

5. Secondary Outcome

Title	Change in Weight
Description	Change in weight from randomization to 72 hours. Secondary Endpoint
Time Frame	randomization to 72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Dose Dopamine	Placebo	Low Dose Nesiritide
Arm/Group Description	Drug: Dopamine Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study 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.	Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization. Placebo: Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.	Drug: Nesiritide Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial. 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.
Measure Participants	122	119	119
Mean (Standard Deviation) [lbs]	-7.40 (7.94)	-7.73 (7.04)	-7.15 (7.80)

6. Secondary Outcome

Title	Worst Reported Symptom Changes-RED-ROSE
Description	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)
Time Frame	Change from Baseline to 72 hours

Outcome Measure Data

Analysis Population Description

RED-ROSE was a substudy of the main ROSE study. Only subjects consented and enrolled in RED-ROSE were included in this analysis.

Arm/Group Title	Low Dose Dopamine	Placebo	Low Dose Nesiritide
Arm/Group Description	Drug: Dopamine Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study 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.	Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization. Placebo: Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.	Drug: Nesiritide Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial. 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.
Measure Participants	68	70	73
Mean (Standard Deviation) [units on a scale]	20.9 (29.6)	19.6 (22.7)	25.6 (25.6)

7. Secondary Outcome

Title	Change in Clinical Stability- RED-ROSE
Description	Change in clinical stability as assessed by 60 day death, re-hospitalization or unscheduled outpatient visit
Time Frame	Baseline to 60 days

Outcome Measure Data

Analysis Population Description

RED-ROSE was a substudy of the main ROSE trial. Only subjects consented and enrolled in RED-ROSE were included in this analysis.

Arm/Group Title	Low Dose Dopamine	Placebo	Low Dose Nesiritide
Arm/Group Description	Drug: Dopamine Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study 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.	Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization. Placebo: Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.	Drug: Nesiritide Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial. 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.
Measure Participants	76	75	76
Number [participants]	30 24.6%	34 28.6%	27 22.7%

8. Secondary Outcome

Title	Change in Serum Creatinine
Time Frame	randomization to 72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Dose Dopamine	Placebo	Low Dose Nesiritide
Arm/Group Description	Drug: Dopamine Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study 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.	Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization. Placebo: Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.	Drug: Nesiritide Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial. 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.
Measure Participants	122	119	119
Mean (Standard Deviation) [mg/dL]	0.00 (0.44)	0.02 (0.33)	0.02 (0.42)

9. Secondary Outcome

Title	Dyspnea Visual Analog Scale Area Under the Curve
Description	Range 0 to 7200 Higher is better
Time Frame	randomization to 72 hours

Outcome Measure Data

Analysis Population Description

Based upon data completeness, sample size for this endpoint does not match the overall ROSE population.

Arm/Group Title	Low Dose Dopamine	Placebo	Low Dose Nesiritide
Arm/Group Description	Drug: Dopamine Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study 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.	Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization. Placebo: Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.	Drug: Nesiritide Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial. 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.
Measure Participants	112	114	115
Mean (Standard Deviation) [units on a scale * hours]	4935.8 (1472.1)	4997.6 (1479.9)	4831.4 (1294.1)

10. Secondary Outcome

Title	Change in Heart Failure Status
Description	Persistent or worsening heart failure defined as need for rescue therapy.
Time Frame	randomization to 72 hours

Outcome Measure Data

Analysis Population Description

Based upon data completeness, sample size for this endpoint does not match the overall ROSE population.

Arm/Group Title	Low Dose Dopamine	Placebo	Low Dose Nesiritide
Arm/Group Description	Drug: Dopamine Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study 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.	Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization. Placebo: Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.	Drug: Nesiritide Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial. 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.
Measure Participants	118	116	117
Number [participants]	11 9%	5 4.2%	6 5%

11. Secondary Outcome

Title	Change in Treatment Response
Description	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
Time Frame	randomization to 72 hours

Outcome Measure Data

Analysis Population Description

Based upon data completeness, sample size for this endpoint does not match the overall ROSE population.

Arm/Group Title	Low Dose Dopamine	Placebo	Low Dose Nesiritide
Arm/Group Description	Drug: Dopamine Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study 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.	Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization. Placebo: Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.	Drug: Nesiritide Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial. 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.
Measure Participants	117	115	119
Number [participants]	35 28.7%	32 26.9%	48 40.3%

12. Secondary Outcome

Title	Cumulative Urinary Sodium Excretion
Time Frame	Randomization to 72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Dose Dopamine	Placebo	Low Dose Nesiritide
Arm/Group Description	Drug: Dopamine Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study 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.	Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization. Placebo: Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.	Drug: Nesiritide Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial. 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.
Measure Participants	122	119	119
Mean (Standard Deviation) [mmol]	527.0 (299.0)	539.8 (302.7)	515.2 (261.4)

13. Secondary Outcome

Title	Change in Blood Urea Nitrogen (BUN)/ Serum Cystatin C Ratio
Description	BUN measured in mg/dL Cystatin C measured in mg/L No units were used in calculated the ratio
Time Frame	Randomization to 72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Dose Dopamine	Placebo	Low Dose Nesiritide
Arm/Group Description	Drug: Dopamine Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study 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.	Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization. Placebo: Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.	Drug: Nesiritide Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial. 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.
Measure Participants	122	119	119
Mean (Standard Deviation) [ratio]	-2.34 (25.33)	0.23 (5.16)	0.74 (7.60)

14. Secondary Outcome

Title	Development of Cardio-renal Syndrome
Time Frame	Randomization to 72 hours

Outcome Measure Data

Analysis Population Description

Based upon data completeness, sample size for this endpoint does not match the overall ROSE population.

Arm/Group Title	Low Dose Dopamine	Placebo	Low Dose Nesiritide
Arm/Group Description	Drug: Dopamine Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study 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.	Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization. Placebo: Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.	Drug: Nesiritide Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial. 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.
Measure Participants	105	110	111
Number [participants]	23 18.9%	24 20.2%	28 23.5%

15. Secondary Outcome

Title	Global Visual Analog Scale Area Under the Curve
Description	Range 0 to 7200 Higher is better/improved
Time Frame	Randomization to 72 hours

Outcome Measure Data

Analysis Population Description

Based upon data completeness, sample size for this endpoint does not match the overall ROSE population.

Arm/Group Title	Low Dose Dopamine	Placebo	Low Dose Nesiritide
Arm/Group Description	Drug: Dopamine Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study 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.	Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization. Placebo: Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.	Drug: Nesiritide Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial. 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.
Measure Participants	112	113	114
Mean (Standard Deviation) [units on a scale * hours]	4553.4 (1324.9)	4703.6 (1403.4)	4498.3 (1301.5)

Adverse Events

Arm/Group Title	Low Dose Dopamine		Placebo		Low Dose Nesiritide
Arm/Group Description	Drug: Dopamine Participants will be randomized to receive low dose dopamine or placebo during first 72 hours of participation in the study 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.		Drug: Placebo Participants will receive placebo in place of low dose dopamine or low dose nesiritide depending on randomization. Placebo: Participants will be randomized to receive Low dose Dopamine or placebo plus optimal diuretic or Low dose Nesiritide or placebo plus optimal diuretic.		Drug: Nesiritide Participants could be randomized to receive low dose nesiritide or placebo during the first 72 hours in the trial. 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.
All Cause Mortality
	Low Dose Dopamine		Placebo		Low Dose Nesiritide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Low Dose Dopamine		Placebo		Low Dose Nesiritide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/122 (24.6%)		24/119 (20.2%)		21/119 (17.6%)
Blood and lymphatic system disorders
Anemia	1/122 (0.8%)		2/119 (1.7%)		0/119 (0%)
Hemorrhagic Anemia	1/122 (0.8%)		0/119 (0%)		0/119 (0%)
Cardiac disorders
Acute Myocardial Infarction	1/122 (0.8%)		0/119 (0%)		0/119 (0%)
Atrioventricular Block, Second Degree	1/122 (0.8%)		0/119 (0%)		0/119 (0%)
Cardiac Arrest	2/122 (1.6%)		2/119 (1.7%)		0/119 (0%)
Paroxysmal Arrhythmia	0/122 (0%)		1/119 (0.8%)		0/119 (0%)
Ventricular Arrhythmia	0/122 (0%)		2/119 (1.7%)		0/119 (0%)
Ear and labyrinth disorders
Ear Pain	0/122 (0%)		0/119 (0%)		1/119 (0.8%)
Eye disorders
Visual Impairment	0/122 (0%)		0/119 (0%)		1/119 (0.8%)
Gastrointestinal disorders
Abdominal Pain	0/122 (0%)		0/119 (0%)		1/119 (0.8%)
Constipation	0/122 (0%)		0/119 (0%)		1/119 (0.8%)
Diarrhea	1/122 (0.8%)		1/119 (0.8%)		0/119 (0%)
Gastroesophogeal Reflux Disease	1/122 (0.8%)		0/119 (0%)		0/119 (0%)
Lower Gastrointestinal Hemorrhage	1/122 (0.8%)		2/119 (1.7%)		1/119 (0.8%)
Melaena	0/122 (0%)		0/119 (0%)		1/119 (0.8%)
Upper Gastrointestinal Hemorrhage	0/122 (0%)		0/119 (0%)		1/119 (0.8%)
Vomitting	1/122 (0.8%)		0/119 (0%)		0/119 (0%)
General disorders
Infusion Site Irritation	1/122 (0.8%)		0/119 (0%)		0/119 (0%)
Chest Discomfort	0/122 (0%)		0/119 (0%)		1/119 (0.8%)
Chest Pain	0/122 (0%)		0/119 (0%)		1/119 (0.8%)
Death	0/122 (0%)		0/119 (0%)		1/119 (0.8%)
Infections and infestations
Cellulitis	1/122 (0.8%)		0/119 (0%)		0/119 (0%)
Influenza	2/122 (1.6%)		0/119 (0%)		0/119 (0%)
Osteomyelitis	0/122 (0%)		1/119 (0.8%)		0/119 (0%)
Pneumonia	2/122 (1.6%)		1/119 (0.8%)		1/119 (0.8%)
Sepsis	4/122 (3.3%)		2/119 (1.7%)		0/119 (0%)
Septic Shock	1/122 (0.8%)		0/119 (0%)		0/119 (0%)
Upper Respiratory Tract Infections	1/122 (0.8%)		0/119 (0%)		0/119 (0%)
Injury, poisoning and procedural complications
Fall	0/122 (0%)		1/119 (0.8%)		0/119 (0%)
Procedural Complications	1/122 (0.8%)		0/119 (0%)		0/119 (0%)
Investigations
Anticoagulation Drug Level Above Therapeutic	2/122 (1.6%)		0/119 (0%)		0/119 (0%)
Weight Decreased	0/122 (0%)		1/119 (0.8%)		0/119 (0%)
Metabolism and nutrition disorders
Hypoglycemia	2/122 (1.6%)		1/119 (0.8%)		1/119 (0.8%)
Hyperammonaemia	0/122 (0%)		0/119 (0%)		1/119 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma	0/122 (0%)		0/119 (0%)		1/119 (0.8%)
Nervous system disorders
Cerebrovascular Accident	1/122 (0.8%)		1/119 (0.8%)		1/119 (0.8%)
Syncope	0/122 (0%)		2/119 (1.7%)		2/119 (1.7%)
Renal and urinary disorders
Renal Failure	0/122 (0%)		3/119 (2.5%)		0/119 (0%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	2/122 (1.6%)		0/119 (0%)		0/119 (0%)
Respiratory Failure	2/122 (1.6%)		1/119 (0.8%)		0/119 (0%)
Vascular disorders
Hypotension	2/122 (1.6%)		7/119 (5.9%)		5/119 (4.2%)
Other (Not Including Serious) Adverse Events
	Low Dose Dopamine		Placebo		Low Dose Nesiritide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/122 (0%)		0/119 (0%)		0/119 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.