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

NCT ID: NCT00608491

Last Updated: 2013-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 188 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2012-06-30

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.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Stepped pharmacologic care

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Ultrafiltration

Intervention Type: DEVICE

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DEVICE

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Nuwellis, Inc.

INDUSTRY

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kerry L. Lee, PhD

Role: PRINCIPAL_INVESTIGATOR

Duke Clinical Research Institute

Locations

Mayo Clinic Arizona

Phoenix, Arizona, United States

Morehouse School of Medicine

Atlanta, Georgia, United States

Minnesota Heart Failure Network

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Duke University Medical Center

Durham, North Carolina, United States

Baylor College of Medicine

Houston, Texas, United States

University of Utah Health Sciences Center

Murray, Utah, United States

University of Vermont - Fletcher Allen Health Care

Burlington, Vermont, United States

Montreal Heart Institute

Montreal, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: RESULT

PMID: 23131078 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31163974 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28130379 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26927285 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26041600 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25543972 (View on PubMed)

Other Identifiers

U01HL084904-04

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01HL084904

Identifier Type: NIH

Identifier Source: secondary_id

View Link

522

Identifier Type: -

Identifier Source: secondary_id

Pro00018064

Identifier Type: -

Identifier Source: org_study_id