Clinical trial NCT00608491: Effectiveness of Ultrafiltration in Treating People With Acute Decompensated Heart Failure and Cardiorenal Syndrome (The CARRESS Study)
Official title: CARdiorenal REScue Study in Acute Decompensated Heart Failure: CARRESS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heart Failure
Keywords: Acute Decompensated Heart Failure
Acute Decompensated Heart Failure With Cardiorenal Syndrome
Cardiorenal Syndrome
Persistent Congestion
Ultra Filtration
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Nuwellis, Inc.
First posted: 2008-02-06
Enrollment: 188
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Change in Serum Creatinine
timeFrame: Change from Baseline to Day 4
measure: Change in Weight
timeFrame: Change from Baseline to Day 4
Secondary outcomes:
measure: Change in Glomerular Filtration Rate
timeFrame: Change from Baseline to Day 4
measure: Change in Serum Creatinine
timeFrame: Change from Baseline to Day 7
measure: Change in Glomerular Filtration Rate
timeFrame: Change from Baseline to Day 7
measure: Changes in Weight
timeFrame: Change from Baseline to Day 1
measure: Changes in Weight
timeFrame: Change from Baseline to Day 2
measure: Change in Weight
timeFrame: Change from Baseline to Day 3
measure: Changes in Weight
timeFrame: Change from Baseline to Day 5
measure: Change in Weight
timeFrame: Change from Baseline to Day 6
measure: Cumulative Net Fluid Loss
timeFrame: Randomization through Day 1
measure: Cumulative Net Fluid Loss
timeFrame: Randomization through Day 2
measure: Cumulative Net Fluid Loss
timeFrame: Randomization through Day 3
measure: Cumulative Net Fluid Loss
timeFrame: Randomization through Day 4
measure: Cumulative Net Fluid Loss
timeFrame: Randomization through Day 5
measure: Cumulative Net Fluid Loss
timeFrame: Randomization through Day 6
measure: Cumulative Net Fluid Loss
timeFrame: Randomization through Day 7
measure: Dyspnea Visual Analog Scale
timeFrame: Change from Baseline to Day 4
measure: Change in Global Visual Analog Scale
timeFrame: Change from Baseline to Day 4
measure: Change in Dyspnea Visual Analog Scale
timeFrame: Baseline to Day 7/Discharge
measure: Change in Global Visual Analog Scale
timeFrame: Baseline to Day 7/Discharge
measure: Change in Furosemide-Equivalent Dose
timeFrame: Baseline to Day 7/Discharge
measure: Change in Blood Sodium Level
timeFrame: Baseline to Day 4
measure: Change in Blood Potassium Level
timeFrame: Baseline to Day 4
measure: Change in Blood Urea Nitrogen/Urea
timeFrame: Baseline to Day 4
measure: Change in Blood Bicarbonate Level
timeFrame: Baseline to Day 4
measure: Change in Blood Hemoglobin Level
timeFrame: Baseline to Day 4
measure: Change in Blood Sodium Level
timeFrame: Baseline to Day 7/Discharge
measure: Change in Blood Potassium Level
timeFrame: Baseline to Day 7/Discharge
measure: Change in Blood Urea Nitrogen/Urea
timeFrame: Baseline to Day 7/Discharge
measure: Change in Blood Bicarbonate Level
timeFrame: Baseline to Day 7/Discharge
measure: Change in Blood Hemoglobin Level
timeFrame: Baseline to Day 7/Discharge
measure: Change in Blood Cystatin C
timeFrame: Baseline to Day 4
measure: Change in Uric Acid
timeFrame: Baseline to Day 4
measure: Change in Blood N- Terminal Pro- BNP
timeFrame: Baseline to Day 4
measure: Change in Plasma Renin Activity
timeFrame: Baseline to Day 4
measure: Change in Blood High Sensitivity Troponin I
timeFrame: Baseline to Day 4
measure: Change in Blood Aldosterone
timeFrame: Baseline to Day 4
measure: Change in Blood Procollagen III N-terminal Propepide
timeFrame: Baseline to Day 4
measure: Change in Blood Endothelin-1
timeFrame: Baseline to Day 4
measure: Change in Blood High Sensitivity C-Reactive Protein
timeFrame: Baseline to Day 4
measure: Change in Blood Carboxy-terminal Telopeptide of Collagen Type I
timeFrame: Baseline to Day 4
measure: Change in Blood Cystatin C
timeFrame: Baseline to Day 7/Discharge
measure: Change in Blood Uric Acid
timeFrame: Baseline to Day 7/Discharge
measure: Change in Blood N Terminal Pro-Natriuretic Peptide
timeFrame: Baseline to Day 7/Discharge
measure: Change in Plasma Renin Activity
timeFrame: Baseline to Day 7/Discharge
measure: Change in Blood High Sensitivity Troponin I
timeFrame: Baseline to Day 7/Discharge
measure: Change in Blood Aldosterone
timeFrame: Baseline to Day 7/Discharge
measure: Change in Blood Procollagen III N-terminal Propepide
timeFrame: Baseline to Day 7/Discharge
measure: Change in Blood Endothelin-1
timeFrame: Baseline to Day 7/Discharge
measure: Change in Blood Carboxy-terminal Telopeptide of Collagen Type I
timeFrame: Baseline to Day 7/Discharge
measure: Change in Blood High Sensitivity C-Reactive Protein
timeFrame: Baseline to Day 7/Discharge
measure: Weight Change
timeFrame: Baseline to Day 30
measure: Change in Furosemide-Equivalent Dose
timeFrame: Baseline to Day 30
measure: Creatinine Change
timeFrame: Baseline to Day 30
measure: Glomerular Filtration Rate Change
timeFrame: Baseline to Day 30
measure: Weight Change
timeFrame: Baseline to Day 60
measure: Change in Furosemide-Equivalent Dose
timeFrame: Baseline to Day 60
measure: Best Available Serum Creatinine Change
timeFrame: Baseline to Day 60
measure: Best Available Glomerular Filtration Rate Change
timeFrame: Baseline to Day 60
measure: Change in Blood Uric Acid
timeFrame: Baseline to Day 60
measure: Change in Blood Cystatin C
timeFrame: Baseline to Day 60
measure: Change in Blood N Terminal Pro - B Natriuretic Peptides
timeFrame: Baseline to Day 60
measure: Change in Plasma Renin Activity
timeFrame: Baseline to Day 60
measure: Change in Blood High Sensitivity Troponin I
timeFrame: Baseline to Day 60
measure: Change in Blood Aldosterone
timeFrame: Baseline to Day 60
measure: Change in Blood Procollagen III N-terminal Propepide
timeFrame: Baseline to Day 60
measure: Change in Blood Endothelin-1
timeFrame: Baseline to Day 60
measure: Change in Blood High Sensitivity C-Reactive Protein
timeFrame: Baseline to Day 60
measure: Change in Blood Carboxy-terminal Telopeptide of Collagen Type I
timeFrame: Baseline to Day 60
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Atlanta
country: United States
facility: Morehouse School of Medicine
state: Georgia
city: Minneapolis
country: United States
facility: Minnesota Heart Failure Network
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Murray
country: United States
facility: University of Utah Health Sciences Center
state: Utah
city: Burlington
country: United States
facility: University of Vermont - Fletcher Allen Health Care
state: Vermont
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
Study officials:
affiliation: Duke Clinical Research Institute
name: Kerry L. Lee, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bart BA, Goldsmith SR, Lee KL, Givertz MM, O'Connor CM, Bull DA, Redfield MM, Deswal A, Rouleau JL, LeWinter MM, Ofili EO, Stevenson LW, Semigran MJ, Felker GM, Chen HH, Hernandez AF, Anstrom KJ, McNulty SE, Velazquez EJ, Ibarra JC, Mascette AM, Braunwald E; Heart Failure Clinical Research Network. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med. 2012 Dec 13;367(24):2296-304. doi: 10.1056/NEJMoa1210357. Epub 2012 Nov 6.
citation: Rao VS, Ahmad T, Brisco-Bacik MA, Bonventre JV, Wilson FP, Siew ED, Felker GM, Anstrom KK, Mahoney DD, Bart BA, Tang WHW, Velazquez EJ, Testani JM. Renal Effects of Intensive Volume Removal in Heart Failure Patients With Preexisting Worsening Renal Function. Circ Heart Fail. 2019 Jun;12(6):e005552. doi: 10.1161/CIRCHEARTFAILURE.118.005552. Epub 2019 Jun 5.
citation: Kitai T, Grodin JL, Kim YH, Tang WH. Impact of Ultrafiltration on Serum Sodium Homeostasis and its Clinical Implication in Patients With Acute Heart Failure, Congestion, and Worsening Renal Function. Circ Heart Fail. 2017 Feb;10(2):e003603. doi: 10.1161/CIRCHEARTFAILURE.116.003603.
citation: de Denus S, Rouleau JL, Mann DL, Huggins GS, Cappola TP, Shah SH, Keleti J, Zada YF, Provost S, Bardhadi A, Phillips MS, Normand V, Mongrain I, Dube MP. A pharmacogenetic investigation of intravenous furosemide in decompensated heart failure: a meta-analysis of three clinical trials. Pharmacogenomics J. 2017 Mar;17(2):192-200. doi: 10.1038/tpj.2016.4. Epub 2016 Mar 1.
citation: Lala A, McNulty SE, Mentz RJ, Dunlay SM, Vader JM, AbouEzzeddine OF, DeVore AD, Khazanie P, Redfield MM, Goldsmith SR, Bart BA, Anstrom KJ, Felker GM, Hernandez AF, Stevenson LW. Relief and Recurrence of Congestion During and After Hospitalization for Acute Heart Failure: Insights From Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart Failure (DOSE-AHF) and Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARESS-HF). Circ Heart Fail. 2015 Jul;8(4):741-8. doi: 10.1161/CIRCHEARTFAILURE.114.001957. Epub 2015 Jun 3.
citation: Mentz RJ, Stevens SR, DeVore AD, Lala A, Vader JM, AbouEzzeddine OF, Khazanie P, Redfield MM, Stevenson LW, O'Connor CM, Goldsmith SR, Bart BA, Anstrom KJ, Hernandez AF, Braunwald E, Felker GM. Decongestion strategies and renin-angiotensin-aldosterone system activation in acute heart failure. JACC Heart Fail. 2015 Feb;3(2):97-107. doi: 10.1016/j.jchf.2014.09.003. Epub 2014 Oct 31.