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

NCT00608491 | Completed Phase 3 Results DMC

• 4 other identifiers: Pro00018064U01HL084904-04U01HL084904522
• Study Type: interventional
• Target: 188
• Locations: 2 countries
• Sites: 9

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.

Conditions

Heart Failure

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Change in Serum Creatinine

  Change from Baseline to Day 4

• Change in Weight

  Change from Baseline to Day 4

Secondary Outcomes (68)

• Change in Glomerular Filtration Rate

  Change from Baseline to Day 4

• Change in Serum Creatinine

  Change from Baseline to Day 7

• Change in Glomerular Filtration Rate

  Change from Baseline to Day 7

• Changes in Weight

  Change from Baseline to Day 1

• Changes in Weight

  Change from Baseline to Day 2

Study Arms (2)

Stepped pharmacologic care

ACTIVE COMPARATOR

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

Ultrafiltration

EXPERIMENTAL

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

Interventions

Stepped pharmacologic care DRUG

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

Stepped pharmacologic care

Ultrafiltration 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.

Ultrafiltration

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Nuwellis, Inc.: collaborator

Study Sites (9)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

Morehouse School of Medicine

Atlanta, Georgia, 30310, United States

Location

Minnesota Heart Failure Network

Minneapolis, Minnesota, 55415, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah Health Sciences Center

Murray, Utah, 84107, United States

Location

University of Vermont - Fletcher Allen Health Care

Burlington, Vermont, 05401, United States

Location

Montreal Heart Institute

Montreal, Quebec, H1T - 1C8, Canada

Location

Related Publications (6)

• 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.

  PMID: 23131078 RESULT

• 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.

  PMID: 31163974 DERIVED

• 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.

  PMID: 28130379 DERIVED

• 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.

  PMID: 26927285 DERIVED

• 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.

  PMID: 26041600 DERIVED

• 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.

  PMID: 25543972 DERIVED

MeSH Terms

Conditions

Heart Failure; Cardio-Renal Syndrome

Interventions

Ultrafiltration

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Extracorporeal Circulation; Surgical Procedures, Operative; Filtration; Chemistry Techniques, Analytical; Investigative Techniques; Physical Phenomena; Chemical Phenomena

Results Point of Contact

• Title: Jenny Ibarra
• Organization: Duke University

jenny.ibarra@duke.edu

9192363291

Study Officials

• Kerry L. Lee, PhD

  Duke Clinical Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2008
• First Posted: February 6, 2008
• Study Start: March 1, 2008
• Primary Completion: March 1, 2012
• Study Completion: June 1, 2012
• Last Updated: June 24, 2013
• Results First Posted: June 24, 2013

Record last verified: 2013-05

Locations

CA (1); US (8)