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

This study has been completed.
Sponsor:
Collaborators:
CHF Solutions
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00608491
First received: January 25, 2008
Last updated: May 15, 2013
Last verified: May 2013
  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: Stepped pharmacologic care
Device: Ultrafiltration
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: CARdiorenal REScue Study in Acute Decompensated Heart Failure: CARRESS

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Change in Serum Creatinine [ Time Frame: Change from Baseline to Day 4 ] [ Designated as safety issue: No ]
  • Change in Weight [ Time Frame: Change from Baseline to Day 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in Glomerular Filtration Rate [ Time Frame: Change from Baseline to Day 4 ] [ Designated as safety issue: No ]
  • Change in Serum Creatinine [ Time Frame: Change from Baseline to Day 7 ] [ Designated as safety issue: No ]
  • Change in Glomerular Filtration Rate [ Time Frame: Change from Baseline to Day 7 ] [ Designated as safety issue: No ]
  • Changes in Weight [ Time Frame: Change from Baseline to Day 1 ] [ Designated as safety issue: No ]
  • Changes in Weight [ Time Frame: Change from Baseline to Day 2 ] [ Designated as safety issue: No ]
  • Change in Weight [ Time Frame: Change from Baseline to Day 3 ] [ Designated as safety issue: No ]
  • Changes in Weight [ Time Frame: Change from Baseline to Day 5 ] [ Designated as safety issue: No ]
  • Change in Weight [ Time Frame: Change from Baseline to Day 6 ] [ Designated as safety issue: No ]
  • Cumulative Net Fluid Loss [ Time Frame: Randomization through Day 1 ] [ Designated as safety issue: No ]
  • Cumulative Net Fluid Loss [ Time Frame: Randomization through Day 2 ] [ Designated as safety issue: No ]
  • Cumulative Net Fluid Loss [ Time Frame: Randomization through Day 3 ] [ Designated as safety issue: No ]
  • Cumulative Net Fluid Loss [ Time Frame: Randomization through Day 4 ] [ Designated as safety issue: No ]
  • Cumulative Net Fluid Loss [ Time Frame: Randomization through Day 5 ] [ Designated as safety issue: No ]
  • Cumulative Net Fluid Loss [ Time Frame: Randomization through Day 6 ] [ Designated as safety issue: No ]
  • Cumulative Net Fluid Loss [ Time Frame: Randomization through Day 7 ] [ Designated as safety issue: No ]
  • Dyspnea Visual Analog Scale [ Time Frame: Change from Baseline to Day 4 ] [ Designated as safety issue: No ]

    Scale range: -100 , +100

    -100=worse, +100=better


  • Change in Global Visual Analog Scale [ Time Frame: Change from Baseline to Day 4 ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline to Day 7/Discharge ] [ Designated as safety issue: No ]

    Scale range: -100 , +100

    -100=worse, +100=better


  • Change in Global Visual Analog Scale [ Time Frame: Baseline to Day 7/Discharge ] [ Designated as safety issue: No ]

    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 Furosemide-Equivalent Dose [ Time Frame: Baseline to Day 7/Discharge ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Day 4 ] [ Designated as safety issue: No ]
  • Change in Blood Potassium Level [ Time Frame: Baseline to Day 4 ] [ Designated as safety issue: No ]
  • Change in Blood Urea Nitrogen/Urea [ Time Frame: Baseline to Day 4 ] [ Designated as safety issue: No ]
  • Change in Blood Bicarbonate Level [ Time Frame: Baseline to Day 4 ] [ Designated as safety issue: No ]
  • Change in Blood Hemoglobin Level [ Time Frame: Baseline to Day 4 ] [ Designated as safety issue: No ]
  • Change in Blood Sodium Level [ Time Frame: Baseline to Day 7/Discharge ] [ Designated as safety issue: No ]
  • Change in Blood Potassium Level [ Time Frame: Baseline to Day 7/Discharge ] [ Designated as safety issue: No ]
  • Change in Blood Urea Nitrogen/Urea [ Time Frame: Baseline to Day 7/Discharge ] [ Designated as safety issue: No ]
  • Change in Blood Bicarbonate Level [ Time Frame: Baseline to Day 7/Discharge ] [ Designated as safety issue: No ]
  • Change in Blood Hemoglobin Level [ Time Frame: Baseline to Day 7/Discharge ] [ Designated as safety issue: No ]
  • Change in Blood Cystatin C [ Time Frame: Baseline to Day 4 ] [ Designated as safety issue: No ]
  • Change in Uric Acid [ Time Frame: Baseline to Day 4 ] [ Designated as safety issue: No ]
  • Change in Blood N- Terminal Pro- BNP [ Time Frame: Baseline to Day 4 ] [ Designated as safety issue: No ]
  • Change in Plasma Renin Activity [ Time Frame: Baseline to Day 4 ] [ Designated as safety issue: No ]
  • Change in Blood High Sensitivity Troponin I [ Time Frame: Baseline to Day 4 ] [ Designated as safety issue: No ]
  • Change in Blood Aldosterone [ Time Frame: Baseline to Day 4 ] [ Designated as safety issue: No ]
  • Change in Blood Procollagen III N-terminal Propepide [ Time Frame: Baseline to Day 4 ] [ Designated as safety issue: No ]
  • Change in Blood Endothelin-1 [ Time Frame: Baseline to Day 4 ] [ Designated as safety issue: No ]
  • Change in Blood High Sensitivity C-Reactive Protein [ Time Frame: Baseline to Day 4 ] [ Designated as safety issue: No ]
  • Change in Blood Carboxy-terminal Telopeptide of Collagen Type I [ Time Frame: Baseline to Day 4 ] [ Designated as safety issue: No ]
  • Change in Blood Cystatin C [ Time Frame: Baseline to Day 7/Discharge ] [ Designated as safety issue: No ]
  • Change in Blood Uric Acid [ Time Frame: Baseline to Day 7/Discharge ] [ Designated as safety issue: No ]
  • Change in Blood N Terminal Pro-Natriuretic Peptide [ Time Frame: Baseline to Day 7/Discharge ] [ Designated as safety issue: No ]
  • Change in Plasma Renin Activity [ Time Frame: Baseline to Day 7/Discharge ] [ Designated as safety issue: No ]
  • Change in Blood High Sensitivity Troponin I [ Time Frame: Baseline to Day 7/Discharge ] [ Designated as safety issue: No ]
  • Change in Blood Aldosterone [ Time Frame: Baseline to Day 7/Discharge ] [ Designated as safety issue: No ]
  • Change in Blood Procollagen III N-terminal Propepide [ Time Frame: Baseline to Day 7/Discharge ] [ Designated as safety issue: No ]
  • Change in Blood Endothelin-1 [ Time Frame: Baseline to Day 7/Discharge ] [ Designated as safety issue: No ]
  • Change in Blood Carboxy-terminal Telopeptide of Collagen Type I [ Time Frame: Baseline to Day 7/Discharge ] [ Designated as safety issue: No ]
  • Change in Blood High Sensitivity C-Reactive Protein [ Time Frame: Baseline to Day 7/Discharge ] [ Designated as safety issue: No ]
  • Weight Change [ Time Frame: Baseline to Day 30 ] [ Designated as safety issue: No ]
  • Change in Furosemide-Equivalent Dose [ Time Frame: Baseline to Day 30 ] [ Designated as safety issue: No ]
    Furosemide-Equivalent Dose is the dose bumetanide or torsemide converted to furosemide equivalent (Torsemide dose x 2,Bumetanide dose x 40)

  • Creatinine Change [ Time Frame: Baseline to Day 30 ] [ Designated as safety issue: No ]
  • Glomerular Filtration Rate Change [ Time Frame: Baseline to Day 30 ] [ Designated as safety issue: No ]
  • Weight Change [ Time Frame: Baseline to Day 60 ] [ Designated as safety issue: No ]
  • Change in Furosemide-Equivalent Dose [ Time Frame: Baseline to Day 60 ] [ Designated as safety issue: No ]
    Furosemide-Equivalent Dose is the dose bumetanide or torsemide converted to furosemide equivalent (Torsemide dose x 2,Bumetanide dose x 40)

  • Best Available Serum Creatinine Change [ Time Frame: Baseline to Day 60 ] [ Designated as safety issue: No ]
    Core laboratory when available. If not available, local laboratory results were used.

  • Best Available Glomerular Filtration Rate Change [ Time Frame: Baseline to Day 60 ] [ Designated as safety issue: No ]
    Core laboratory when available. If not available, local laboratory results were used.

  • Change in Blood Uric Acid [ Time Frame: Baseline to Day 60 ] [ Designated as safety issue: No ]
  • Change in Blood Cystatin C [ Time Frame: Baseline to Day 60 ] [ Designated as safety issue: No ]
  • Change in Blood N Terminal Pro - B Natriuretic Peptides [ Time Frame: Baseline to Day 60 ] [ Designated as safety issue: No ]
  • Change in Plasma Renin Activity [ Time Frame: Baseline to Day 60 ] [ Designated as safety issue: No ]
  • Change in Blood High Sensitivity Troponin I [ Time Frame: Baseline to Day 60 ] [ Designated as safety issue: No ]
  • Change in Blood Aldosterone [ Time Frame: Baseline to Day 60 ] [ Designated as safety issue: No ]
  • Change in Blood Procollagen III N-terminal Propepide [ Time Frame: Baseline to Day 60 ] [ Designated as safety issue: No ]
  • Change in Blood Endothelin-1 [ Time Frame: Baseline to Day 60 ] [ Designated as safety issue: No ]
  • Change in Blood High Sensitivity C-Reactive Protein [ Time Frame: Baseline to Day 60 ] [ Designated as safety issue: No ]
  • Change in Blood Carboxy-terminal Telopeptide of Collagen Type I [ Time Frame: Baseline to Day 60 ] [ Designated as safety issue: No ]

Enrollment: 188
Study Start Date: March 2008
Study Completion Date: June 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
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.
Experimental: 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.
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:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Arizona
Mayo Clinic Arizona
Phoenix, Arizona, United States, 85054
United States, Georgia
Morehouse School of Medicine
Atlanta, Georgia, United States, 30310
United States, Minnesota
Minnesota Heart Failure Network
Minneapolis, Minnesota, United States, 55415
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27705
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
United States, Utah
University of Utah Health Sciences Center
Murray, Utah, United States, 84107
United States, Vermont
University of Vermont - Fletcher Allen Health Care
Burlington, Vermont, United States, 05401
Canada, Quebec
Montreal Heart Institute
Montreal, Quebec, Canada, H1T - 1C8
Sponsors and Collaborators
Duke University
CHF Solutions
Investigators
Principal Investigator: Kerry L. Lee, PhD Duke Clinical Research Institute
  More Information

Publications:
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00608491     History of Changes
Other Study ID Numbers: Pro00018064, U01HL084904-04, U01 HL084904, 522
Study First Received: January 25, 2008
Results First Received: February 18, 2013
Last Updated: May 15, 2013
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by Duke University:
Acute Decompensated Heart Failure
Acute Decompensated Heart Failure With Cardiorenal Syndrome
Cardiorenal Syndrome
Persistent Congestion
Ultra Filtration

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014