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

Sponsors and Collaborators:	National Heart, Lung, and Blood Institute (NHLBI) CHF Solutions
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00608491

Purpose

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.

Condition	Intervention	Phase
Heart Failure	Drug: Standard medical drug therapy Device: Ultrafiltration	Phase III

MedlinePlus related topics: Heart Failure

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment
Official Title:	CARdiorenal REScue Study in Acute Decompensated Heart Failure: CARRESS

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

Change in serum creatinine and weight together as a "bivariate" endpoint [ Time Frame: Measured at Days 1, 2, 3, 4, and 7 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	200
Study Start Date:	March 2008
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Participants will receive standard medical drug therapy	Drug: Standard medical drug therapy Standard medical drug therapy will include stepped pharmacological care. Stepped care will provide treating physicians with guidelines for the intensification of diuretic therapy and the possible use of vasodilators and inotropes.
2: Experimental Participants will receive ultrafiltration	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.

Arms

Assigned Interventions

1: Active Comparator

Participants will receive standard medical drug therapy

Drug: Standard medical drug therapy

Standard medical drug therapy will include stepped pharmacological care. Stepped care will provide treating physicians with guidelines for the intensification of diuretic therapy and the possible use of vasodilators and inotropes.

2: Experimental

Participants will receive ultrafiltration

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.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Admitted to the hospital with a primary diagnosis of decompensated heart failure
Onset of cardiorenal syndrome after hospitalization (must occur within 7 days from the time of admission after receiving IV diuretics) or before hospitalization (must occur in the 6 weeks before hospitalization in the setting of escalating doses of outpatient loop diuretics)
Persistent volume overload (for participant with a pulmonary artery catheter, persistent volume overload will include pulmonary capillary wedge pressure greater than 22 mmHg and one of the following clinical signs: at least 2+ peripheral edema and/or pulmonary edema or pleural effusions on chest x-ray; for participant without a pulmonary artery catheter, persistent volume overload will include at least two of the following clinical signs: at least 2+ peripheral edema, jugular venous pressure greater than 10 cm on physical examination [or central venous pressure greater than 10 mmHg when measured], or pulmonary edema or pleural effusions on chest x-ray)

Exclusion Criteria:

Intravascular volume depletion based on investigator's clinical assessment
Acute coronary syndrome within the 4 weeks prior to study entry
Indication for hemodialysis
Creatinine greater than 3.5 mg per deciliter at admission to the hospital
Systolic blood pressure less than 90 mmHg at study entry
Alternative explanation for worsening renal function, such as obstructive nephropathy, contrast-induced nephropathy, or acute tubular necrosis
Hematocrit greater than 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
Use of iodinated radiocontrast material in the 72 hours before study entry 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00608491

Locations

United States, Georgia
Morehouse School of Medicine	Recruiting
Atlanta, Georgia, United States, 30310
Contact: Elizabeth Ofili, MD 404-752-1970 eofili@msm.edu
Contact: Brenda Lankford, RN, PhD 404-756-1377 blankford@msm.edu
Principal Investigator: Elizabeth Ofili, MD
Sub-Investigator: Anekwe Onwuanyi, MD
United States, Minnesota
Mayo Clinic	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Margaret M. Redfield, MD 507-284-1281 redfield.margaret@mayo.edu
Contact: Jilian Foxen 919-284-1281 foxen.jilian@mayo.edu
Principal Investigator: Margaret M. Redfield, MD
Sub-Investigator: John Burnett, MD
Sub-Investigator: Horng Chen, MD
Minnesota Heart Failure Network	Recruiting
Minneapolis, Minnesota, United States, 55415
Contact: Steven R. Goldsmith, MD 612-347-2875 srg_hcmc@yahoo.com
Contact: Shari Mackedanz, RN, BSN 612-347-5195 shari.mackedanz@co.hennepin.mn.us
Principal Investigator: Steven R. Goldsmith, MD
Sub-Investigator: Bradley Bart, MD
United States, North Carolina
Duke University Medical Center	Recruiting
Durham, North Carolina, United States, 27705
Contact: Christopher O'Connor, MD 919-880-6787 oconn002@mc.duke.edu
Contact: Patti Adams, RN 919-668-8222 patricia.adams@duke.edu
Principal Investigator: Christopher O'Conner, MD
Sub-Investigator: Michael Felker, MD, MHS
Sub-Investigator: Larry Allen, MD
Sub-Investigator: Joseph Rogers, MD
Sub-Investigator: Carmelo Milano, MD
United States, Texas
Baylor College of Medicine	Recruiting
Houston, Texas, United States, 77030
Contact: Douglas Mann, MD 713-798-0285 dmann@bcm.tmc.edu
Contact: Mary Soliz 713-798-0270 adeswal@bcm.tmc.edu
Principal Investigator: Doug Mann, MD
Sub-Investigator: Anita Deswal, MD, MPH
United States, Utah
University of Utah Health Sciences Center	Recruiting
Murray, Utah, United States, 84107
Contact: David Bull, MD 801-585-3936 david.bull@hsc.utah.edu
Contact: Bev Campbell 801-408-5715 bev.campbell@intermountainmail.org
Principal Investigator: David Bull, MD
Sub-Investigator: Dean Li, MD
Sub-Investigator: Dale Renlund, MD
United States, Vermont
University of Vermont - Fletcher Allen Health Care	Recruiting
Burlington, Vermont, United States, 05401
Contact: Martin LeWinter, MD 802-847-2879 martin.lewinter@vtmednet.org
Contact: Michaelanne Rowen, RN 802-847-4746 michaelanne.rowen@vtmednet.org
Principal Investigator: Martin LeWinter, MD
Sub-Investigator: Markus Meyer, MD
Sub-Investigator: Richard Pratley, MD
Sub-Investigator: Peter VanBuren, MD
Canada, Quebec
Montreal Heart Institute	Recruiting
Montreal, Quebec, Canada, H1T - 1C8
Contact: Jean Rouleau, MD 514-343-6351 jean.rouleau@umontreal.ca
Contact: Mady Benhaim 514-376-3330 ext 3935 lucette.whittom@icm-mhi.org
Principal Investigator: Jean Rouleau, MD
Sub-Investigator: Normand Racine, MD

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

CHF Solutions

Investigators

Principal Investigator:

Kerry L. Lee, PhD

Duke University

More Information

Responsible Party:	Duke Clinical Research Institute ( Kerry L. Lee, PhD )
Study ID Numbers:	522, U01 HL084904
Study First Received:	January 25, 2008
Last Updated:	October 14, 2008
ClinicalTrials.gov Identifier:	NCT00608491
Health Authority:	United States: Federal Government

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):

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

Study placed in the following topic categories:

Heart Failure
Heart Diseases

Additional relevant MeSH terms:

Cardiovascular Diseases

ClinicalTrials.gov processed this record on January 16, 2009