Study of Heart Failure Hospitalizations After Aquapheresis Therapy Compared to Intravenous (IV) Diuretic Treatment

NCT01474200 | Terminated Results DMC

• 1 other identifier: 1494
• Study Type: interventional
• Target: 224
• Locations: 1 country
• Sites: 38

Brief Summary

The purpose of the research is to determine if patients have fewer Heart Failure (HF) events after receiving Aquapheresis (AQ) therapy compared to intravenous (IV) diuretics up to 90 days of discharge from the hospital. Heart Failure events are defined as returning to the hospital, clinic or emergency department (ED) for treatment of HF symptoms.

Conditions

Heart Failure; Cardiac Failure; Acute Decompensated Heart Failure (ADHF)

Keywords

Ultrafiltration; Aquapheresis; Diuretics; Loop Diuretics; Aquadex Flexflow System; Gambro UF Solutions

Outcome Measures

Primary Outcomes (1)

• Time to First Heart Failure (HF) Event

  Time to first HF event within 90 days after discharge from index HF hospitalization. HF events are defined as * HF rehospitalization or * unscheduled outpatient or emergency room treatment with IV loop diuretics or * unscheduled outpatient Aquapheresis treatment

  90 days after discharge from index HF hospitalization.

Secondary Outcomes (22)

• EFFICACY: Total Fluid Removed During the Index Hospitalization

  Index Hospitalization, an average of 8 days

• EFFICACY: Net Fluid Removed During the Index Hospitalization

  Index Hospitalization, an average of 8 days

• EFFICACY: Weight Loss at 72 Hours After Initiation of Treatment

  72 hours after treatment initiation

• EFFICACY: Total Weight Loss During the Index Hospitalization

  Index Hospitalization, an average of 8 days

• EFFICACY: Time to Freedom From Congestion

  Index Hospitalization, an average of 8 days

Study Arms (2)

Aquapheresis (AQ) - isolated veno-venous ultrafiltration

EXPERIMENTAL

Excess fluid from the patient is removed by isolated veno-venous ultrafiltration treatment using the Aquadex Flex Flow System

Device: Isolated veno-venous ultrafiltration (AQ)

IV Loop Diuretics (LD)

ACTIVE COMPARATOR

Excess fluid from the patient is removed by IV (Intravenous) loop diuretic treatment

Drug: IV Loop Diuretics (LD)

Interventions

Isolated veno-venous ultrafiltration (AQ) DEVICE

Aquapheresis treatment (isolated veno-venous ultrafiltration) using the Aquadex FlexFlow System during index hospitalization until the patient's signs and symptoms of fluid overload have improved to the satisfaction of the treating physician. Ultrafiltration rates, duration and frequency of treatment are dependent on the amount of patient fluid excess and on the rate of fluid movement from the interstitial spaces into the vascular compartment during Aquapheresis (Plasma Refill Rate, or PRR)

Also known as: Aquapheresis, Ultrafiltration, Aquadex FlexFlow System, Gambro UF Solutions

Aquapheresis (AQ) - isolated veno-venous ultrafiltration

IV Loop Diuretics (LD) DRUG

IV Loop Diuretics treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload. This includes furosemide or other IV loop diuretics administered at equivalent doses to furosemide. Patients will receive either a twice daily IV bolus or continuous IV LD infusions according to the high dose protocol of the"Diuretic strategies in patients wth acute decompensated heart failure" (DOSE) trial.

Also known as: furosemide

IV Loop Diuretics (LD)

Eligibility Criteria

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

You may qualify if:

• years of age or older
• Male or non-pregnant female patients
• Admitted to the hospital with a primary diagnosis of acute decompensated heart failure (ADHF)
• On regularly scheduled oral loop diuretics prior to admission
• Fluid overload manifested by at least two of the following:
• Pitting edema (2+) of the lower extremities
• Jugular venous distention \> 8 cm
• Pulmonary edema or pleural effusion on chest x-ray
• Paroxysmal nocturnal dyspnea or ≥ two- pillow orthopnea
• Respiration rate ≥ 20 per minute.
• Have received ≤ 2 IV loop diuretics doses before randomization
• Must be able to be enrolled into the trial ≤ 24 hours of their admission to the hospital.
• Provide written informed consent form as required by the local IRB (Institutional Review Board)

You may not qualify if:

• Acute coronary syndromes
• Renal insufficiency with a sCr ≥ 3.0 mg/dl or planned renal replacement therapies
• Systolic blood pressure \< 90 mmHg at time of enrollment
• Pulmonary Arterial Hypertension not secondary to left heart disease
• Contraindications to systemic anticoagulation
• Hematocrit \> 45%
• Inability to obtain venous access
• Hemodynamic instability severe enough to require IV positive inotropic agents, IV vasodilators or both
• Use of iodinated radiocontrast material within the previous 72 hours or planned study requiring IV contrast during the current hospitalization
• Severe concomitant disease expected to prolong hospitalization
• Severe concomitant disease expected to cause death in ≤ 90 days
• Sepsis or ongoing systemic infection
• Severe uncorrected valvular stenosis
• Active myocarditis
• Hypertrophic obstructive cardiomyopathy

Sponsors & Collaborators

• Nuwellis, Inc.: lead

Study Sites (38)

Heart Center Research

Huntsville, Alabama, 35801, United States

Location

Mayo Clinic - Scottsdale

Scottsdale, Arizona, 85054, United States

Location

Scottsdale Healthcare Research Institute

Scottsdale, Arizona, 85258, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

University of California, San Diego (UCSD)

San Diego, California, 92037, United States

Location

San Diego Cardiac Center

San Diego, California, 92123, United States

Location

Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Morton Plant Medical Center

Clearwater, Florida, 33756, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Evanston, Illinois, 60208, United States

Location

Edward Hospital Center for Advanced Heart Failure

Naperville, Illinois, 60566, United States

Location

Advocate Health & Hospitals Corporation

Oakbrook Terrace, Illinois, 60181, United States

Location

Elkhart General HealthCare

Elkhart, Indiana, 46514, United States

Location

Northern Indiana Research Alliance

Fort Wayne, Indiana, 46804, United States

Location

Iowa Health - Des Moines

Des Moines, Iowa, 50316, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

Minneapolis VA Medical Center

Minneapolis, Minnesota, 55417, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Saint Luke's Hospital and Saint Luke's Cardiovascular Consultants

Kansas City, Missouri, 64111, United States

Location

AtlantiCare Health Network

Egg Harbor, New Jersey, 08234, United States

Location

New Mexico Heart Institute/Heart Hospital

Albuquerque, New Mexico, 87102, United States

Location

Asheville Cardiology Associates

Asheville, North Carolina, 28803, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

MetroHealth Systems

Cleveland, Ohio, 44109, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Good Samaritan Hospital - Dayton

Dayton, Ohio, 45415, United States

Location

Oklahoma Heart Institute and Hillcrest Medical Center

Tulsa, Oklahoma, 74104, United States

Location

Abington Memorial Hospital

Abington, Pennsylvania, 19001, United States

Location

St. Luke's Hospital and Health Network

Bethlehem, Pennsylvania, 18018, United States

Location

Drexel University College of Medicine

Philadelphia, Pennsylvania, 19102, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Albert Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

Saint Thomas Hospital

Nashville, Tennessee, 37205, United States

Location

Brooke Army Medical Center

San Antonio, Texas, 78234, United States

Location

Virginia Commonwealth University Medical Center

Richmond, Virginia, 23298, United States

Location

MultiCare Health System/Tacoma General Hospital

Tacoma, Washington, 98405, United States

Location

Aurora St. Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States

Location

Related Publications (12)

• Costanzo MR, Guglin ME, Saltzberg MT, Jessup ML, Bart BA, Teerlink JR, Jaski BE, Fang JC, Feller ED, Haas GJ, Anderson AS, Schollmeyer MP, Sobotka PA; UNLOAD Trial Investigators. Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure. J Am Coll Cardiol. 2007 Feb 13;49(6):675-83. doi: 10.1016/j.jacc.2006.07.073. Epub 2007 Jan 26.

  PMID: 17291932 BACKGROUND

• Adams KF Jr, Fonarow GC, Emerman CL, LeJemtel TH, Costanzo MR, Abraham WT, Berkowitz RL, Galvao M, Horton DP; ADHERE Scientific Advisory Committee and Investigators. Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J. 2005 Feb;149(2):209-16. doi: 10.1016/j.ahj.2004.08.005.

  PMID: 15846257 BACKGROUND

• Jain P, Massie BM, Gattis WA, Klein L, Gheorghiade M. Current medical treatment for the exacerbation of chronic heart failure resulting in hospitalization. Am Heart J. 2003 Feb;145(2 Suppl):S3-17. doi: 10.1067/mhj.2003.149. No abstract available.

  PMID: 12594447 BACKGROUND

• Drazner MH, Rame JE, Stevenson LW, Dries DL. Prognostic importance of elevated jugular venous pressure and a third heart sound in patients with heart failure. N Engl J Med. 2001 Aug 23;345(8):574-81. doi: 10.1056/NEJMoa010641.

  PMID: 11529211 BACKGROUND

• Domanski M, Norman J, Pitt B, Haigney M, Hanlon S, Peyster E; Studies of Left Ventricular Dysfunction. Diuretic use, progressive heart failure, and death in patients in the Studies Of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol. 2003 Aug 20;42(4):705-8. doi: 10.1016/s0735-1097(03)00765-4.

  PMID: 12932605 BACKGROUND

• Sharma A, Hermann DD, Mehta RL. Clinical benefit and approach of ultrafiltration in acute heart failure. Cardiology. 2001;96(3-4):144-54. doi: 10.1159/000047398.

  PMID: 11805381 BACKGROUND

• Marenzi G, Lauri G, Grazi M, Assanelli E, Campodonico J, Agostoni P. Circulatory response to fluid overload removal by extracorporeal ultrafiltration in refractory congestive heart failure. J Am Coll Cardiol. 2001 Oct;38(4):963-8. doi: 10.1016/s0735-1097(01)01479-6.

  PMID: 11583865 BACKGROUND

• Rimondini A, Cipolla CM, Della Bella P, Grazi S, Sisillo E, Susini G, Guazzi MD. Hemofiltration as short-term treatment for refractory congestive heart failure. Am J Med. 1987 Jul;83(1):43-8. doi: 10.1016/0002-9343(87)90495-5.

  PMID: 3605181 BACKGROUND

• Jaski BE, Ha J, Denys BG, Lamba S, Trupp RJ, Abraham WT. Peripherally inserted veno-venous ultrafiltration for rapid treatment of volume overloaded patients. J Card Fail. 2003 Jun;9(3):227-31. doi: 10.1054/jcaf.2003.28.

  PMID: 12815573 BACKGROUND

• Bart BA, Boyle A, Bank AJ, Anand I, Olivari MT, Kraemer M, Mackedanz S, Sobotka PA, Schollmeyer M, Goldsmith SR. Ultrafiltration versus usual care for hospitalized patients with heart failure: the Relief for Acutely Fluid-Overloaded Patients With Decompensated Congestive Heart Failure (RAPID-CHF) trial. J Am Coll Cardiol. 2005 Dec 6;46(11):2043-6. doi: 10.1016/j.jacc.2005.05.098. Epub 2005 Nov 4.

  PMID: 16325039 BACKGROUND

• Costanzo MR, Saltzberg M, O'Sullivan J, Sobotka P. Early ultrafiltration in patients with decompensated heart failure and diuretic resistance. J Am Coll Cardiol. 2005 Dec 6;46(11):2047-51. doi: 10.1016/j.jacc.2005.05.099. Epub 2005 Nov 9.

  PMID: 16325040 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Heart Failure

Interventions

Ultrafiltration; Sodium Potassium Chloride Symporter Inhibitors; Furosemide

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Extracorporeal Circulation; Surgical Procedures, Operative; Filtration; Chemistry Techniques, Analytical; Investigative Techniques; Physical Phenomena; Chemical Phenomena; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds

Limitations and Caveats

Due to patient recruitment challenges, the study was terminated early. At that time, no interim analyses of the data had been completed; therefore the decision to close the study was not related to any underlying concerns about safety or futility.

Results Point of Contact

• Title: Drew Jones, MD, Senior Medical Director
• Organization: Baxter Healthcare Corporation

drew_jones@baxter.com

224-270-2659

Study Officials

• Maria Rosa Costanzo, MD

  Midwest Heart Foundation

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2011
• First Posted: November 18, 2011
• Study Start: January 1, 2012
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: August 29, 2023
• Results First Posted: October 12, 2015

Record last verified: 2023-08

Locations

US (38)