Effectiveness of Ultrafiltration in Treating People With Acute Decompensated Heart Failure and Cardiorenal Syndrome (The CARRESS Study)

Study Overview
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Brief Summary
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Heart failure is a serious condition in which the heart's ability to pump blood through the body is impaired, often making a person feel weak or fatigued. When a person's condition worsens to the point of hospitalization, that person is said to have acute decompensated heart failure (ADHF). Abnormal kidney function in association with cardiac distress, known as cardiorenal syndrome, is a common complication of heart failure and causes further medical problems and need for hospitalization. While there are various effective treatments for heart failure, more research is needed to determine the best treatment for targeting both ADHF and cardiorenal syndrome. This study will compare the safety and effectiveness of ultrafiltration versus standard medical drug therapy in improving renal function and relieving fluid buildup in people hospitalized with ADHF and cardiorenal syndrome.

Detailed Description
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Heart failure is a common condition that affects approximately 5 million people in the United States, with 550,000 new cases diagnosed each year. Common symptoms of heart failure include swelling and fluid buildup in the legs, feet, and/or lungs; shortness of breath; coughing; elevated heart rate; change in appetite; and fatigue. If left untreated, the condition of the heart may deteriorate so far that the person undergoes ADHF. The number of hospitalizations attributed to ADHF has risen significantly, with many people readmitted soon after discharge because of recurring symptoms or further medical complications, such as cardiorenal syndrome. Current heart failure treatments focus on removing excess fluid buildup, often by increasing urination with diuretic medications or by draining directly from the veins. Direct drainage from the veins, also known as ultrafiltration, may be the more effective method for treating people with ADHF and cardiorenal syndrome. This study will compare the safety and effectiveness of ultrafiltration versus standard medical drug therapy in improving renal function and relieving fluid buildup in people hospitalized with ADHF and cardiorenal syndrome. Participation in this study will last 60 days. All potential participants will undergo initial screening, which will include a medical history, physical exam, blood draws, measurements of fluid intake and urine output, and questionnaires. These same evaluations and procedures will be repeated at various points during the hospital stay. Eligible participants will be randomly assigned to receive standard medical drug therapy or fluid removal by ultrafiltration. Standard medical drug therapy will involve the intravenous delivery of diuretics and possibly other doctor-recommended medications. Ultrafiltration will involve intravenously removing blood, passing it through an ultrafiltration device, and then returning the blood to the participant. During ultrafiltration, participants will be treated with a blood thinner through the IV, as well. Follow-up assessments will occur at Days 30 and 60 after treatment. Follow-up assessments will include measurements of fluid intake, urine output, and vital signs; blood draws; physical exams; and questions about medications and status of recovery.

Official Title
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CARdiorenal REScue Study in Acute Decompensated Heart Failure: CARRESS

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Stepped pharmacologic care
* Device: Ultrafiltration


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: age 18 or older admitted to the hospital with a primary diagnosis of decompensated heart failure onset of cardiorenal syndrome after hospitalization or pre-hospitalization after hospitalization - onset of cardiorenal syndrome after hospitalization must occur within 10 days from the time of admission after receiving IV diuretics pre-hospitalization - onset of cardiorenal syndrome pre-hospitalization must occur within 12 weeks of the index hospitalization in the setting of escalating doses of outpatient diuretics persistent volume overload Exclusion criteria: intravascular volume depletion based on investigators clinical assessment acute coronary syndrome within 4 weeks indication for hemodialysis creatinine > 3.5 mg per deciliter at admission to the hospital systolic blood pressure < 90 mmHg at the time of enrollment alternative explanation for worsening renal function such as obstructive nephropathy,contrast induced nephropathy, acute tubular necrosis Hematocrit > 45% poor venous access clinical instability likely to require the addition of intravenous vasoactive drugs including vasodilators and/or inotropic agents allergy or contraindications to the use of heparin the use of iodinated radio contrast material in the last 72 hours or anticipated use of IV contrast during the current hospitalization known bilateral renal artery stenosis active myocarditis hypertrophic obstructive cardiomyopathy severe valvular stenosis complex congenital heart disease sepsis or ongoing systemic infection enrollment in another clinical trial involving medical or device based interventions

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Stepped pharmacologic care<br>Stepped care will provide treating physicians with guidelines for the intensification of diuretic therapy and the possible use of vasodilators and inotropes. | Drug: Stepped pharmacologic care<br>* Stepped care will provide treating physicians with guidelines for the intensification of diuretic therapy and the possible use of vasodilators and inotropes.<br>|
| Experimental: Ultrafiltration<br>All loop diuretics will be discontinued. Treatment will involve slow continuous ultrafiltration until an optimal volume status has been achieved. Ultrafiltration therapy will be initiated after the placement of appropriate intravenous access and will continue until the participant's signs and symptoms of congestion have been optimized. Fluid status will be managed exclusively by ultrafiltration using the Aquadex system 100 (CHF Solutions, Inc.) according to the manufacturer's specifications. The use of vasodilators or inotropic agents will be prohibited unless deemed necessary for rescue therapy. | Device: Ultrafiltration<br>* All loop diuretics will be discontinued. Treatment will involve slow continuous ultrafiltration until an optimal volume status has been achieved. Ultrafiltration therapy will be initiated after the placement of appropriate intravenous access and will continue until the participant's signs and symptoms of congestion have been optimized. Fluid status will be managed exclusively by ultrafiltration using the Aquadex system 100 (CHF Solutions, Inc.) according to the manufacturer's specifications. The use of vasodilators or inotropic agents will be prohibited unless deemed necessary for rescue therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum Creatinine |  | Change from Baseline to Day 4 | 
| Change in Weight |  | Change from Baseline to Day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glomerular Filtration Rate |  | Change from Baseline to Day 4 | 
| Change in Serum Creatinine |  | Change from Baseline to Day 7 | 
| Change in Glomerular Filtration Rate |  | Change from Baseline to Day 7 | 
| Changes in Weight |  | Change from Baseline to Day 1 | 
| Changes in Weight |  | Change from Baseline to Day 2 | 
| Change in Weight |  | Change from Baseline to Day 3 | 
| Changes in Weight |  | Change from Baseline to Day 5 | 
| Change in Weight |  | Change from Baseline to Day 6 | 
| Cumulative Net Fluid Loss |  | Randomization through Day 1 | 
| Cumulative Net Fluid Loss |  | Randomization through Day 2 | 
| Cumulative Net Fluid Loss |  | Randomization through Day 3 | 
| Cumulative Net Fluid Loss |  | Randomization through Day 4 | 
| Cumulative Net Fluid Loss |  | Randomization through Day 5 | 
| Cumulative Net Fluid Loss |  | Randomization through Day 6 | 
| Cumulative Net Fluid Loss |  | Randomization through Day 7 | 
| Dyspnea Visual Analog Scale | Scale range: -100 , +100 -100=worse, +100=better | Change from Baseline to Day 4 | 
| Change in Global Visual Analog Scale | Scale range: -100 , +100 -100=worse, +100=better Participants asked to mark their global well being on a 10 cm vertical line, with the top labeled best you have ever felt and the bottom labeled worst you have ever felt. | Change from Baseline to Day 4 | 
| Change in Dyspnea Visual Analog Scale | Scale range: -100 , +100 -100=worse, +100=better | Baseline to Day 7/Discharge | 
| Change in Global Visual Analog Scale | Scale range: -100 , +100 -100=worse, +100=better Participants asked to mark their global well being on a 10 cm vertical line, with the top labeled best you have ever felt and the bottom labeled worst you have ever felt. | Baseline to Day 7/Discharge | 
| Change in Furosemide-Equivalent Dose | Furosemide-Equivalent Dose is the dose bumetanide or torsemide converted to furosemide equivalent (Torsemide dose x 2,Bumetanide dose x 40) | Baseline to Day 7/Discharge | 
| Change in Blood Sodium Level |  | Baseline to Day 4 | 
| Change in Blood Potassium Level |  | Baseline to Day 4 | 
| Change in Blood Urea Nitrogen/Urea |  | Baseline to Day 4 | 
| Change in Blood Bicarbonate Level |  | Baseline to Day 4 | 
| Change in Blood Hemoglobin Level |  | Baseline to Day 4 | 
| Change in Blood Sodium Level |  | Baseline to Day 7/Discharge | 
| Change in Blood Potassium Level |  | Baseline to Day 7/Discharge | 
| Change in Blood Urea Nitrogen/Urea |  | Baseline to Day 7/Discharge | 
| Change in Blood Bicarbonate Level |  | Baseline to Day 7/Discharge | 
| Change in Blood Hemoglobin Level |  | Baseline to Day 7/Discharge | 
| Change in Blood Cystatin C |  | Baseline to Day 4 | 
| Change in Uric Acid |  | Baseline to Day 4 | 
| Change in Blood N- Terminal Pro- BNP |  | Baseline to Day 4 | 
| Change in Plasma Renin Activity |  | Baseline to Day 4 | 
| Change in Blood High Sensitivity Troponin I |  | Baseline to Day 4 | 
| Change in Blood Aldosterone |  | Baseline to Day 4 | 
| Change in Blood Procollagen III N-terminal Propepide |  | Baseline to Day 4 | 
| Change in Blood Endothelin-1 |  | Baseline to Day 4 | 
| Change in Blood High Sensitivity C-Reactive Protein |  | Baseline to Day 4 | 
| Change in Blood Carboxy-terminal Telopeptide of Collagen Type I |  | Baseline to Day 4 | 
| Change in Blood Cystatin C |  | Baseline to Day 7/Discharge | 
| Change in Blood Uric Acid |  | Baseline to Day 7/Discharge | 
| Change in Blood N Terminal Pro-Natriuretic Peptide |  | Baseline to Day 7/Discharge | 
| Change in Plasma Renin Activity |  | Baseline to Day 7/Discharge | 
| Change in Blood High Sensitivity Troponin I |  | Baseline to Day 7/Discharge | 
| Change in Blood Aldosterone |  | Baseline to Day 7/Discharge | 
| Change in Blood Procollagen III N-terminal Propepide |  | Baseline to Day 7/Discharge | 
| Change in Blood Endothelin-1 |  | Baseline to Day 7/Discharge | 
| Change in Blood Carboxy-terminal Telopeptide of Collagen Type I |  | Baseline to Day 7/Discharge | 
| Change in Blood High Sensitivity C-Reactive Protein |  | Baseline to Day 7/Discharge | 
| Weight Change |  | Baseline to Day 30 | 
| Change in Furosemide-Equivalent Dose | Furosemide-Equivalent Dose is the dose bumetanide or torsemide converted to furosemide equivalent (Torsemide dose x 2,Bumetanide dose x 40) | Baseline to Day 30 | 
| Creatinine Change |  | Baseline to Day 30 | 
| Glomerular Filtration Rate Change |  | Baseline to Day 30 | 
| Weight Change |  | Baseline to Day 60 | 
| Change in Furosemide-Equivalent Dose | Furosemide-Equivalent Dose is the dose bumetanide or torsemide converted to furosemide equivalent (Torsemide dose x 2,Bumetanide dose x 40) | Baseline to Day 60 | 
| Best Available Serum Creatinine Change | Core laboratory when available. If not available, local laboratory results were used. | Baseline to Day 60 | 
| Best Available Glomerular Filtration Rate Change | Core laboratory when available. If not available, local laboratory results were used. | Baseline to Day 60 | 
| Change in Blood Uric Acid |  | Baseline to Day 60 | 
| Change in Blood Cystatin C |  | Baseline to Day 60 | 
| Change in Blood N Terminal Pro - B Natriuretic Peptides |  | Baseline to Day 60 | 
| Change in Plasma Renin Activity |  | Baseline to Day 60 | 
| Change in Blood High Sensitivity Troponin I |  | Baseline to Day 60 | 
| Change in Blood Aldosterone |  | Baseline to Day 60 | 
| Change in Blood Procollagen III N-terminal Propepide |  | Baseline to Day 60 | 
| Change in Blood Endothelin-1 |  | Baseline to Day 60 | 
| Change in Blood High Sensitivity C-Reactive Protein |  | Baseline to Day 60 | 
| Change in Blood Carboxy-terminal Telopeptide of Collagen Type I |  | Baseline to Day 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Decompensated Heart Failure, Acute Decompensated Heart Failure With Cardiorenal Syndrome, Cardiorenal Syndrome, Persistent Congestion, Ultra Filtration