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

• Significant weight loss and renal improvement [ Time Frame: Measured at Days 4 and 7 ] [ Designated as safety issue: No ]
• Treatment failure [ Time Frame: Measured at Days 1, 2, 3, 4, 5, 6, and 7 ] [ Designated as safety issue: Yes ]
• Changes in renal function (peak creatinine during hospitalization) [ Time Frame: Measured at Days 7, 30, and 60 ] [ Designated as safety issue: No ]
• Changes in electrolytes [ Time Frame: Measured at Days 4 and 7 ] [ Designated as safety issue: No ]
• Changes in weight [ Time Frame: Measured at Days 7, 30, and 60 ] [ Designated as safety issue: No ]
• Clinical decongestion [ Time Frame: Measured at Days 4, 7, 30, and 60 ] [ Designated as safety issue: No ]
• Total net fluid loss [ Time Frame: Measured at Days 4 and 7 ] [ Designated as safety issue: No ]
• Changes in biomarkers [ Time Frame: Measured at Days 4, 7, and 60 ] [ Designated as safety issue: No ]
• Changes in global assessment and visual analogue scores [ Time Frame: Measured at Days 4 and 7 ] [ Designated as safety issue: No ]
• Length of hospital stay [ Time Frame: Measured from enrollment to discharge ] [ Designated as safety issue: No ]
• Changes in daily oral diuretic doses [ Time Frame: Measured before hospitalization, at discharge, and at Days 30 and 60 ] [ Designated as safety issue: No ]

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.

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.

• Drug: Stepped pharmacologic care
  Stepped care will provide treating physicians with guidelines for the intensification of diuretic therapy and the possible use of vasodilators and inotropes.
• Device: Ultrafiltration
  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.

• Active Comparator: 1
  Participants will receive stepped pharmacologic care
  Intervention: Drug: Stepped pharmacologic care
• Experimental: 2
  Participants will receive ultrafiltration
  Intervention: Device: Ultrafiltration

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 investigator‟s 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

• National Heart, Lung, and Blood Institute (NHLBI)
• CHF Solutions