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

Acute Heart Failure Clinical Trial

— ROSE/RED ROSE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01132846
• Other study ID #: Pro00024136
• Secondary ID: U01HL084904Pro00
• Status: Completed
• Phase: Phase 2
• First received: May 27, 2010
• Last updated: August 20, 2014
• Start date: August 2010
• Est. completion date: June 2013

Study information

• Verified date: August 2014
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 360
• Est. completion date: June 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Heart Failure
• Heart Failure

Intervention

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.

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.
• 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.

Locations

Country	Name	City	State
Canada	Montreal Heart Institute	Montreal	Quebec
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	University of Vermont- Fletcher Allen Health Care	Burlington	Vermont
United States	Duke University Medical Center	Durham	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Minnesota Heart Failure Network	Minneapolis	Minnesota
United States	University of Utah Health Sciences Center	Murry	Utah
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

Chen HH, Anstrom KJ, Givertz MM, Stevenson LW, Semigran MJ, Goldsmith SR, Bart BA, Bull DA, Stehlik J, LeWinter MM, Konstam MA, Huggins GS, Rouleau JL, O'Meara E, Tang WH, Starling RC, Butler J, Deswal A, Felker GM, O'Connor CM, Bonita RE, Margulies KB, C — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Cystatin C	The primary Safety endpoint is change in serum cystatin C from randomization to 72 hours.	Randomization to 72 hours	Yes
Primary	Change in Dyspnea Assessment (RED-ROSE Substudy)	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	Baseline to 72 hours	No
Primary	Decongestive Changes- RED-ROSE	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.	Baseline to 72 hours	No
Primary	Cumulative Urinary Volume	The primary efficacy endpoint is cumulative urinary volume (UV; +/- indwelling urinary catheter) at 72 hours	Randomization to 72 hours	No
Secondary	Change in Weight	Change in weight from randomization to 72 hours. Secondary Endpoint	randomization to 72 hours	No
Secondary	Worst Reported Symptom Changes-RED-ROSE	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 from Baseline to 72 hours	No
Secondary	Change in Clinical Stability- RED-ROSE	Change in clinical stability as assessed by 60 day death, re-hospitalization or unscheduled outpatient visit	Baseline to 60 days	No
Secondary	Change in Serum Creatinine		randomization to 72 hours	No
Secondary	Dyspnea Visual Analog Scale Area Under the Curve	Range 0 to 7200 Higher is better	randomization to 72 hours	No
Secondary	Change in Heart Failure Status	Persistent or worsening heart failure defined as need for rescue therapy.	randomization to 72 hours	No
Secondary	Change in Treatment Response	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	randomization to 72 hours	No
Secondary	Cumulative Urinary Sodium Excretion		Randomization to 72 hours	No
Secondary	Change in Blood Urea Nitrogen (BUN)/ Serum Cystatin C Ratio	BUN measured in mg/dL Cystatin C measured in mg/L; No units were used in calculated the ratio	Randomization to 72 hours	No
Secondary	Development of Cardio-renal Syndrome		Randomization to 72 hours	No
Secondary	Global Visual Analog Scale Area Under the Curve	Range 0 to 7200 Higher is better/improved	Randomization to 72 hours	No