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

Heart Failure Clinical Trial

— CARRESS  

Official title:

CARdiorenal REScue Study in Acute Decompensated Heart Failure: CARRESS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00608491
• Other study ID #: Pro00018064
• Secondary ID: U01HL084904-04U0
• Status: Completed
• Phase: Phase 3
• First received: January 25, 2008
• Last updated: May 15, 2013
• Start date: March 2008
• Est. completion date: June 2012

Study information

• Verified date: May 2013
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 188
• Est. completion date: June 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardio-Renal Syndrome
• Heart Failure

Intervention

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.

Locations

Country	Name	City	State
Canada	Montreal Heart Institute	Montreal	Quebec
United States	Morehouse School of Medicine	Atlanta	Georgia
United States	University of Vermont - Fletcher Allen Health Care	Burlington	Vermont
United States	Duke University Medical Center	Durham	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Minnesota Heart Failure Network	Minneapolis	Minnesota
United States	University of Utah Health Sciences Center	Murray	Utah
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Duke University	CHF Solutions, National Heart, Lung, and Blood Institute (NHLBI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Serum Creatinine		Change from Baseline to Day 4	No
Primary	Change in Weight		Change from Baseline to Day 4	No
Secondary	Change in Glomerular Filtration Rate		Change from Baseline to Day 4	No
Secondary	Change in Serum Creatinine		Change from Baseline to Day 7	No
Secondary	Change in Glomerular Filtration Rate		Change from Baseline to Day 7	No
Secondary	Changes in Weight		Change from Baseline to Day 1	No
Secondary	Changes in Weight		Change from Baseline to Day 2	No
Secondary	Change in Weight		Change from Baseline to Day 3	No
Secondary	Changes in Weight		Change from Baseline to Day 5	No
Secondary	Change in Weight		Change from Baseline to Day 6	No
Secondary	Cumulative Net Fluid Loss		Randomization through Day 1	No
Secondary	Cumulative Net Fluid Loss		Randomization through Day 2	No
Secondary	Cumulative Net Fluid Loss		Randomization through Day 3	No
Secondary	Cumulative Net Fluid Loss		Randomization through Day 4	No
Secondary	Cumulative Net Fluid Loss		Randomization through Day 5	No
Secondary	Cumulative Net Fluid Loss		Randomization through Day 6	No
Secondary	Cumulative Net Fluid Loss		Randomization through Day 7	No
Secondary	Dyspnea Visual Analog Scale	Scale range: -100 , +100; -100=worse, +100=better	Change from Baseline to Day 4	No
Secondary	Change in Global Visual Analog Scale	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 from Baseline to Day 4	No
Secondary	Change in Dyspnea Visual Analog Scale	Scale range: -100 , +100; -100=worse, +100=better	Baseline to Day 7/Discharge	No
Secondary	Change in Global Visual Analog Scale	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".	Baseline to Day 7/Discharge	No
Secondary	Change in Furosemide-Equivalent Dose	Furosemide-Equivalent Dose is the dose bumetanide or torsemide converted to furosemide equivalent (Torsemide dose x 2,Bumetanide dose x 40)	Baseline to Day 7/Discharge	No
Secondary	Change in Blood Sodium Level		Baseline to Day 4	No
Secondary	Change in Blood Potassium Level		Baseline to Day 4	No
Secondary	Change in Blood Urea Nitrogen/Urea		Baseline to Day 4	No
Secondary	Change in Blood Bicarbonate Level		Baseline to Day 4	No
Secondary	Change in Blood Hemoglobin Level		Baseline to Day 4	No
Secondary	Change in Blood Sodium Level		Baseline to Day 7/Discharge	No
Secondary	Change in Blood Potassium Level		Baseline to Day 7/Discharge	No
Secondary	Change in Blood Urea Nitrogen/Urea		Baseline to Day 7/Discharge	No
Secondary	Change in Blood Bicarbonate Level		Baseline to Day 7/Discharge	No
Secondary	Change in Blood Hemoglobin Level		Baseline to Day 7/Discharge	No
Secondary	Change in Blood Cystatin C		Baseline to Day 4	No
Secondary	Change in Uric Acid		Baseline to Day 4	No
Secondary	Change in Blood N- Terminal Pro- BNP		Baseline to Day 4	No
Secondary	Change in Plasma Renin Activity		Baseline to Day 4	No
Secondary	Change in Blood High Sensitivity Troponin I		Baseline to Day 4	No
Secondary	Change in Blood Aldosterone		Baseline to Day 4	No
Secondary	Change in Blood Procollagen III N-terminal Propepide		Baseline to Day 4	No
Secondary	Change in Blood Endothelin-1		Baseline to Day 4	No
Secondary	Change in Blood High Sensitivity C-Reactive Protein		Baseline to Day 4	No
Secondary	Change in Blood Carboxy-terminal Telopeptide of Collagen Type I		Baseline to Day 4	No
Secondary	Change in Blood Cystatin C		Baseline to Day 7/Discharge	No
Secondary	Change in Blood Uric Acid		Baseline to Day 7/Discharge	No
Secondary	Change in Blood N Terminal Pro-Natriuretic Peptide		Baseline to Day 7/Discharge	No
Secondary	Change in Plasma Renin Activity		Baseline to Day 7/Discharge	No
Secondary	Change in Blood High Sensitivity Troponin I		Baseline to Day 7/Discharge	No
Secondary	Change in Blood Aldosterone		Baseline to Day 7/Discharge	No
Secondary	Change in Blood Procollagen III N-terminal Propepide		Baseline to Day 7/Discharge	No
Secondary	Change in Blood Endothelin-1		Baseline to Day 7/Discharge	No
Secondary	Change in Blood Carboxy-terminal Telopeptide of Collagen Type I		Baseline to Day 7/Discharge	No
Secondary	Change in Blood High Sensitivity C-Reactive Protein		Baseline to Day 7/Discharge	No
Secondary	Weight Change		Baseline to Day 30	No
Secondary	Change in Furosemide-Equivalent Dose	Furosemide-Equivalent Dose is the dose bumetanide or torsemide converted to furosemide equivalent (Torsemide dose x 2,Bumetanide dose x 40)	Baseline to Day 30	No
Secondary	Creatinine Change		Baseline to Day 30	No
Secondary	Glomerular Filtration Rate Change		Baseline to Day 30	No
Secondary	Weight Change		Baseline to Day 60	No
Secondary	Change in Furosemide-Equivalent Dose	Furosemide-Equivalent Dose is the dose bumetanide or torsemide converted to furosemide equivalent (Torsemide dose x 2,Bumetanide dose x 40)	Baseline to Day 60	No
Secondary	Best Available Serum Creatinine Change	Core laboratory when available. If not available, local laboratory results were used.	Baseline to Day 60	No
Secondary	Best Available Glomerular Filtration Rate Change	Core laboratory when available. If not available, local laboratory results were used.	Baseline to Day 60	No
Secondary	Change in Blood Uric Acid		Baseline to Day 60	No
Secondary	Change in Blood Cystatin C		Baseline to Day 60	No
Secondary	Change in Blood N Terminal Pro - B Natriuretic Peptides		Baseline to Day 60	No
Secondary	Change in Plasma Renin Activity		Baseline to Day 60	No
Secondary	Change in Blood High Sensitivity Troponin I		Baseline to Day 60	No
Secondary	Change in Blood Aldosterone		Baseline to Day 60	No
Secondary	Change in Blood Procollagen III N-terminal Propepide		Baseline to Day 60	No
Secondary	Change in Blood Endothelin-1		Baseline to Day 60	No
Secondary	Change in Blood High Sensitivity C-Reactive Protein		Baseline to Day 60	No
Secondary	Change in Blood Carboxy-terminal Telopeptide of Collagen Type I		Baseline to Day 60	No