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

Aquapheresis Versus Intravenous Diuretics and Hospitalizations for Heart Failure (AVOID-HF)

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.

Study Overview

• Status: Terminated
• Conditions: Heart Failure; Cardiac Failure; Acute Decompensated Heart Failure (ADHF)
• Intervention / Treatment: Device: Isolated veno-venous ultrafiltration (AQ); Drug: IV Loop Diuretics (LD)

Detailed Description

The aim of the proposed AVOID-HF study is to confirm and expand the findings that fluid removal by AQ reduces HF rehospitalizations at 90 days as well as the length of these HF rehospitalizations. In the "Ultrafiltration Versus Intravenous Diuretics for Patients Hospitalized for Acute Decompensated Heart Failure" (UNLOAD) study, the 90 day HF re-hospitalizations were pre-specified secondary end-points. AVOID-HF is designed with a primary end-point to determine if AQ reduces the number of HF events (Rehospitalization or unscheduled outpatient or emergency room treatment for HF) after discharge from index hospitalization compared to IV loop diuretics. AVOID will also explore days alive and out of the hospital as a secondary end-point, which was not done in UNLOAD. In other words, the AVOID-HF study is going beyond studying only the amount of fluid removal and will explore whether the modality of fluid removal influences HF outcomes.

• Study Type: Interventional
• Enrollment (Actual): 224
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Heart Center Research
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Scottsdale Healthcare Research Institute
    • Scottsdale, Arizona, United States, 85054
      • Mayo Clinic - Scottsdale
  • California
    • Los Angeles, California, United States, 90095
      • UCLA
    • San Diego, California, United States, 92123
      • San Diego Cardiac Center
    • San Diego, California, United States, 92037
      • University of California, San Diego (UCSD)
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Florida
    • Clearwater, Florida, United States, 33756
      • Morton Plant Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Evanston, Illinois, United States, 60208
      • Northwestern University
    • Naperville, Illinois, United States, 60566
      • Edward Hospital Center for Advanced Heart Failure
    • Oakbrook Terrace, Illinois, United States, 60181
      • Advocate Health & Hospitals Corporation
  • Indiana
    • Elkhart, Indiana, United States, 46514
      • Elkhart General Healthcare
    • Fort Wayne, Indiana, United States, 46804
      • Northern Indiana Research Alliance
  • Iowa
    • Des Moines, Iowa, United States, 50316
      • Iowa Health - Des Moines
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Minneapolis VA Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital and Saint Luke's Cardiovascular Consultants
  • New Jersey
    • Egg Harbor Township, New Jersey, United States, 08234
      • AtlantiCare Health Network
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • New Mexico Heart Institute/Heart Hospital
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Asheville Cardiology Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44109
      • Metrohealth Systems
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
    • Dayton, Ohio, United States, 45415
      • Good Samaritan Hospital - Dayton
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Oklahoma Heart Institute and Hillcrest Medical Center
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Bethlehem, Pennsylvania, United States, 18018
      • St. Luke's Hospital and Health Network
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Medical Center
    • Philadelphia, Pennsylvania, United States, 19102
      • Drexel University College of Medicine
  • Tennessee
    • Nashville, Tennessee, United States, 37205
      • Saint Thomas Hospital
  • Texas
    • San Antonio, Texas, United States, 78234
      • Brooke Army Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Medical Center
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Health System/Tacoma General Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora St. Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18 years of age or older
2. Male or non-pregnant female patients
3. Admitted to the hospital with a primary diagnosis of acute decompensated heart failure (ADHF)
4. On regularly scheduled oral loop diuretics prior to admission

5. Fluid overload manifested by at least two of the following:

   1. Pitting edema (2+) of the lower extremities
   2. Jugular venous distention > 8 cm
   3. Pulmonary edema or pleural effusion on chest x-ray
   4. Paroxysmal nocturnal dyspnea or ≥ two- pillow orthopnea
   5. Respiration rate ≥ 20 per minute.
6. Have received ≤ 2 IV loop diuretics doses before randomization
7. Must be able to be enrolled into the trial ≤ 24 hours of their admission to the hospital.
8. Provide written informed consent form as required by the local IRB (Institutional Review Board)

Exclusion Criteria:

1. Acute coronary syndromes
2. Renal insufficiency with a sCr ≥ 3.0 mg/dl or planned renal replacement therapies
3. Systolic blood pressure < 90 mmHg at time of enrollment
4. Pulmonary Arterial Hypertension not secondary to left heart disease
5. Contraindications to systemic anticoagulation
6. Hematocrit > 45%
7. Inability to obtain venous access
8. Hemodynamic instability severe enough to require IV positive inotropic agents, IV vasodilators or both
9. Use of iodinated radiocontrast material within the previous 72 hours or planned study requiring IV contrast during the current hospitalization
10. Severe concomitant disease expected to prolong hospitalization
11. Severe concomitant disease expected to cause death in ≤ 90 days
12. Sepsis or ongoing systemic infection
13. Severe uncorrected valvular stenosis
14. Active myocarditis
15. Hypertrophic obstructive cardiomyopathy
16. Constrictive pericarditis or restrictive cardiomyopathy
17. Liver cirrhosis
18. Previous solid organ transplant
19. Requirement for mechanical ventilatory support
20. Presence of a mechanical circulatory support device
21. Unwillingness or inability to complete follow up
22. Active drug or ETOH substance abuse
23. Participating in another interventional clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aquapheresis (AQ) - isolated veno-venous ultrafiltration; 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); 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); Other Names: Ultrafiltration; Aquapheresis; Aquadex FlexFlow System; Gambro UF Solutions
Active Comparator: IV Loop Diuretics (LD); Excess fluid from the patient is removed by IV (Intravenous) loop diuretic treatment	Drug: IV Loop Diuretics (LD); 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.; Other Names: furosemide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
EFFICACY: Total Fluid Removed During the Index Hospitalization	AQ-Fluid removed by AQ plus urine voided versus urine voided when treated with IV diuretics	Index Hospitalization, an average of 8 days
EFFICACY: Net Fluid Removed During the Index Hospitalization	AQ-Fluid removed by AQ plus urine voided minus fluid intake versus urine voided minus fluid intake with the IV diuretics.	Index Hospitalization, an average of 8 days
EFFICACY: Weight Loss at 72 Hours After Initiation of Treatment	Weight at 72 hours after treatment initiation minus weight at treatment initiation. Negative mean values indicate weight loss.	72 hours after treatment initiation
EFFICACY: Total Weight Loss During the Index Hospitalization	Weight at hospital discharge minus weight at hospital admission. Negative mean values indicate weight loss.	Index Hospitalization, an average of 8 days
EFFICACY: Time to Freedom From Congestion	Time from hospital admission to time patient is free of congestion in the hospital. Freedom from congestion is defined as jugular venous distention of < or equal to 8 cm, with no orthopnea and with trace peripheral edema or no edema. Measurement taken every 24 hours after treatment initiation.	Index Hospitalization, an average of 8 days
EFFICACY: Freedom From Congestion	Defined as jugular venous distention of < or equal to 8 cm, with no orthopnea, and with trace peripheral edema or no edema at hospital discharge	Index Hospitalization, an average of 8 days
EFFICACY: Changes in B-type Natriuretic Peptide (BNP) Levels Over Time	Change in BNP levels over time at 72 hours, discharge, and 90 days after discharge.	Baseline and at 72 hours from baseline, hospital discharge and at 90 days after hospital discharge
CLINICAL: Total Number of Days Rehospitalized for Heart Failure (HF) at 30 and 90 Days After Discharge	Days rehospitalized for HF symptoms requiring hospital, emergency room or clinic treatment involving the use of IV diuretics and /or positive inotropic or vasodilator drugs.	Within 30 days and 90 days after hospital discharge
CLINICAL: Total Number of Emergency Department (ED) or Unscheduled Office Visits at 30 and 90 Days After Discharge	Number of visits for HF symptoms requiring ED or clinic treatment involving the use of IV diuretics and /or positive inotropic or vasodilator drugs	Within 30 days and 90 days after hospital discharge
CLINICAL: Total Number of Heart Failure (HF) Rehospitalizations at 30 and 90 Days After Discharge	Number of different times patient was admitted to hospital for HF symptoms within 90 days of index hospitalization discharge.	Within 30 days and 90 days after hospital discharge
CLINICAL: Total Number of Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge	CV symptoms that required hospitalization for treatment within 90 days of index hospitalization discharge.	Within 30 days and 90 days after hospital discharge
CLINICAL: Total Number of Days for Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge	The total number of days spent in the hospital due to CV related events at 30 days and 90 days from hospital discharge.	Within 30 days and 90 days after hospital discharge
CLINICAL: All Cause Rehospitalization Rates at 30 and 90 Days	Any cause that required hospitalization for treatment within 90 days of index hospitalization discharge.	Within 30 days and 90 days after hospital discharge
CLINICAL: Global Clinical Score at 30 and 90 Days After Discharge	KCCQ Questionnaire analysis based on patient's self-assessment of how they feel at various intervals compared to how they felt prior to index treatment. Scores were transformed to a range of 0-100, in which higher scores reflect better health status.	Within 90 days after hospital discharge
SAFETY: Changes in Renal Function (Serum Creatinine) After Treatment up to 90 Days After Randomization	Changes in renal function prior to index treatment compared to various intervals by assessing the patient's serum creatinine (sCr), Blood Urea Nitrogen(BUN), BUN/sCr ratio and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula	Within 90 days of randomization
SAFETY: Changes in Renal Function (Blood Urea Nitrogen) After Treatment up to 90 Days After Randomization	Changes in renal function prior to index treatment compared to various intervals by assessing the patient's serum creatinine (sCr), Blood Urea Nitrogen(BUN), BUN/sCr ratio and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula	Within 90 days of randomization
SAFETY: Changes in Renal Function (Blood Urea Nitrogen/Serum Creatinine) After Treatment up to 90 Days After Randomization	Changes in renal function prior to index treatment compared to various intervals by assessing the patient's serum creatinine (sCr), Blood Urea Nitrogen(BUN), BUN/sCr ratio and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula	Within 90 days of randomization
SAFETY: Changes in Renal Function (Estimated Glomerular Filtration Rate) After Treatment up to 90 Days After Randomization	Changes in renal function prior to index treatment compared to various intervals by assessing the patient's serum creatinine (sCr), Blood Urea Nitrogen(BUN), BUN/sCr ratio and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula	Within 90 days of randomization
Length of Stay (LOS) During the Index Hospitalization	Number of days patient is in hospital for HF treatment.	Index hospitalization admission to index hospitalization discharge
Mortality Rates Within Index Hospitalization or Within 90 Days After Hospital Discharge.	Death due to any cause within index hospitalization and 90 days following hospital discharge.	Time from randomization to 90 days post-hospital discharge
Days Alive and Out of Hospital at 30 and 90 Days After Discharge	Number of days patients were alive and out of the hospital at 30 and 90 days after discharge.	Within 30 and 90 days after hospital discharge
Quality of Life Assessed Using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 30, 60 and 90 Days After Discharge	Questionnaire assessed patients quality of life prior to index treatment versus timeframes following hospital discharge. Scores were transformed to a range of 0-100, in which higher scores reflect better health status.	Within 90 days after hospital discharge

Collaborators and Investigators

• Sponsor: Nuwellis, Inc.
• Investigators: Principal Investigator: Maria Rosa Costanzo, MD, Midwest Heart Foundation

Publications and helpful links

General Publications

• 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.
• 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. Erratum In: J Am Coll Cardiol. 2007 Mar 13;49(10):1136.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: November 11, 2011
• First Submitted That Met QC Criteria: November 15, 2011
• First Posted (Estimated): November 18, 2011

Study Record Updates

• Last Update Posted (Actual): August 29, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Diuretics; Ultrafiltration; Loop Diuretics; Aquapheresis; Aquadex Flexflow System; Gambro UF Solutions
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Furosemide; Diuretics; Sodium Potassium Chloride Symporter Inhibitors
• Other Study ID Numbers: 1494 (CSL Behring)