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

CARdiorenal REScue Study in Acute Decompensated Heart Failure: CARRESS

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00608491

Acronym

CARRESS

Enrollment

188

Registered

2008-02-06

Start date

2008-03-31

Completion date

2012-06-30

Last updated

2013-06-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Heart Failure

Keywords

Acute Decompensated Heart Failure, Acute Decompensated Heart Failure With Cardiorenal Syndrome, Cardiorenal Syndrome, Persistent Congestion, Ultra Filtration

Brief summary

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

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.

Interventions

DRUGStepped pharmacologic care

Stepped care will provide treating physicians with guidelines for the intensification of diuretic therapy and the possible use of vasodilators and inotropes.

DEVICEUltrafiltration

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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame
Change in Serum Creatinine	Change from Baseline to Day 4
Change in Weight	Change from Baseline to Day 4

Secondary

Measure	Time frame	Description
Changes in Weight	Change from Baseline to Day 1	—
Change in Weight	Change from Baseline to Day 3	—
Cumulative Net Fluid Loss	Randomization through Day 1	—
Dyspnea Visual Analog Scale	Change from Baseline to Day 4	Scale range: -100 , +100 -100=worse, +100=better
Change in Global Visual Analog Scale	Change from Baseline to Day 4	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 in Dyspnea Visual Analog Scale	Baseline to Day 7/Discharge	Scale range: -100 , +100 -100=worse, +100=better
Change in Furosemide-Equivalent Dose	Baseline to Day 7/Discharge	Furosemide-Equivalent Dose is the dose bumetanide or torsemide converted to furosemide equivalent (Torsemide dose x 2,Bumetanide dose x 40)
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 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 Glomerular Filtration Rate	Change from 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 Uric Acid	Baseline to Day 7/Discharge	—
Change in Blood N Terminal Pro-Natriuretic Peptide	Baseline to Day 7/Discharge	—
Weight Change	Baseline to Day 30	—
Creatinine Change	Baseline to Day 30	—
Glomerular Filtration Rate Change	Baseline to Day 30	—
Best Available Serum Creatinine Change	Baseline to Day 60	Core laboratory when available. If not available, local laboratory results were used.
Best Available Glomerular Filtration Rate Change	Baseline to Day 60	Core laboratory when available. If not available, local laboratory results were used.
Change in Blood N Terminal Pro - B Natriuretic Peptides	Baseline to Day 60	—
Change in Plasma Renin Activity	Baseline to Day 4	—
Change in Serum Creatinine	Change from Baseline to Day 7	—

Countries

Canada, United States

Participant flow

Participants by arm

Arm	Count
Stepped Pharmacologic Care Participants will receive stepped pharmacologic care	94
Ultrafiltration Participants will receive ultrafiltration	94
Total	188

Baseline characteristics

Characteristic	Total	Stepped Pharmacologic Care	Ultrafiltration
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	111 Participants	52 Participants	59 Participants
Age, Categorical Between 18 and 65 years	77 Participants	42 Participants	35 Participants
Age Continuous	68.0 years STANDARD_DEVIATION 12.9	67.1 years STANDARD_DEVIATION 13.7	68.9 years STANDARD_DEVIATION 12
Sex: Female, Male Female	47 Participants	26 Participants	21 Participants
Sex: Female, Male Male	141 Participants	68 Participants	73 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	0 / 94	0 / 94
serious Total, serious adverse events	54 / 94	68 / 94