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

Sponsor
Nuwellis, Inc. (Industry)
Overall Status
Terminated
CT.gov ID
NCT01474200
Collaborator
(none)
224
Enrollment
38
Locations
2
Arms
30
Duration (Months)
5.9
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Device: Isolated veno-venous ultrafiltration (AQ)
  • Drug: IV Loop Diuretics (LD)
 N/A

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 Design

Study Type:
Interventional
Actual Enrollment :
224 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Aquapheresis Versus Intravenous Diuretics and Hospitalizations for Heart Failure (AVOID-HF)
Study Start Date :
Jan 1, 2012
Actual Primary Completion Date :
Jul 1, 2014
Actual Study Completion Date :
Jul 1, 2014

Arms and Interventions

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:
  • Aquapheresis
  • Ultrafiltration
  • 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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Time to First Heart Failure (HF) Event [90 days after discharge from index HF hospitalization.]

      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

    Secondary Outcome Measures

    1. EFFICACY: Total Fluid Removed During the Index Hospitalization [Index Hospitalization, an average of 8 days]

      AQ-Fluid removed by AQ plus urine voided versus urine voided when treated with IV diuretics

    2. EFFICACY: Net Fluid Removed During the Index Hospitalization [Index Hospitalization, an average of 8 days]

      AQ-Fluid removed by AQ plus urine voided minus fluid intake versus urine voided minus fluid intake with the IV diuretics.

    3. EFFICACY: Weight Loss at 72 Hours After Initiation of Treatment [72 hours after treatment initiation]

      Weight at 72 hours after treatment initiation minus weight at treatment initiation. Negative mean values indicate weight loss.

    4. EFFICACY: Total Weight Loss During the Index Hospitalization [Index Hospitalization, an average of 8 days]

      Weight at hospital discharge minus weight at hospital admission. Negative mean values indicate weight loss.

    5. EFFICACY: Time to Freedom From Congestion [Index Hospitalization, an average of 8 days]

      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.

    6. EFFICACY: Freedom From Congestion [Index Hospitalization, an average of 8 days]

      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

    7. EFFICACY: Changes in B-type Natriuretic Peptide (BNP) Levels Over Time [Baseline and at 72 hours from baseline, hospital discharge and at 90 days after hospital discharge]

      Change in BNP levels over time at 72 hours, discharge, and 90 days after discharge.

    8. CLINICAL: Length of Stay (LOS) During the Index Hospitalization [Index hospitalization admission to index hospitalization discharge]

      Number of days patient is in hospital for HF treatment.

    9. CLINICAL: Total Number of Days Rehospitalized for Heart Failure (HF) at 30 and 90 Days After Discharge [Within 30 days and 90 days after hospital 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.

    10. CLINICAL: Total Number of Emergency Department (ED) or Unscheduled Office Visits at 30 and 90 Days After Discharge [Within 30 days and 90 days after hospital 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

    11. CLINICAL: Total Number of Heart Failure (HF) Rehospitalizations at 30 and 90 Days After Discharge [Within 30 days and 90 days after hospital discharge]

      Number of different times patient was admitted to hospital for HF symptoms within 90 days of index hospitalization discharge.

    12. CLINICAL: Total Number of Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge [Within 30 days and 90 days after hospital discharge]

      CV symptoms that required hospitalization for treatment within 90 days of index hospitalization discharge.

    13. CLINICAL: Total Number of Days for Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge [Within 30 days and 90 days after hospital discharge]

      The total number of days spent in the hospital due to CV related events at 30 days and 90 days from hospital discharge.

    14. CLINICAL: All Cause Rehospitalization Rates at 30 and 90 Days [Within 30 days and 90 days after hospital discharge]

      Any cause that required hospitalization for treatment within 90 days of index hospitalization discharge.

    15. CLINICAL: Mortality Rates Within Index Hospitalization or Within 90 Days After Hospital Discharge. [Time from randomization to 90 days post-hospital discharge]

      Death due to any cause.

    16. CLINICAL: Days Alive and Out of Hospital at 30 and 90 Days After Discharge [Within 30 and 90 days after hospital discharge]

      Number of days patients were alive and out of the hospital.

    17. CLINICAL: Quality of Life Assessed Using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 30, 60 and 90 Days After Discharge [Within 90 days after hospital 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.

    18. CLINICAL: Global Clinical Score at 30 and 90 Days After Discharge [Within 90 days after hospital 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.

    19. SAFETY: Changes in Renal Function (Serum Creatinine) After Treatment up to 90 Days After Randomization [Within 90 days of 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

    20. SAFETY: Changes in Renal Function (Blood Urea Nitrogen) After Treatment up to 90 Days After Randomization [Within 90 days of 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

    21. SAFETY: Changes in Renal Function (Blood Urea Nitrogen/Serum Creatinine) After Treatment up to 90 Days After Randomization [Within 90 days of 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

    22. SAFETY: Changes in Renal Function (Estimated Glomerular Filtration Rate) After Treatment up to 90 Days After Randomization [Within 90 days of 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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:

    6. Pitting edema (2+) of the lower extremities

    7. Jugular venous distention > 8 cm

    8. Pulmonary edema or pleural effusion on chest x-ray

    9. Paroxysmal nocturnal dyspnea or ≥ two- pillow orthopnea

    10. Respiration rate ≥ 20 per minute.

    11. Have received ≤ 2 IV loop diuretics doses before randomization

    12. Must be able to be enrolled into the trial ≤ 24 hours of their admission to the hospital.

    13. 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Heart Center Research Huntsville Alabama United States 35801
    2 Mayo Clinic - Scottsdale Scottsdale Arizona United States 85054
    3 Scottsdale Healthcare Research Institute Scottsdale Arizona United States 85258
    4 UCLA Los Angeles California United States 90095
    5 University of California, San Diego (UCSD) San Diego California United States 92037
    6 San Diego Cardiac Center San Diego California United States 92123
    7 Washington Hospital Center Washington District of Columbia United States 20010
    8 Morton Plant Medical Center Clearwater Florida United States 33756
    9 Emory University Atlanta Georgia United States 30322
    10 Northwestern University Evanston Illinois United States 60208
    11 Edward Hospital Center for Advanced Heart Failure Naperville Illinois United States 60566
    12 Advocate Health & Hospitals Corporation Oakbrook Terrace Illinois United States 60181
    13 Elkhart General HealthCare Elkhart Indiana United States 46514
    14 Northern Indiana Research Alliance Fort Wayne Indiana United States 46804
    15 Iowa Health - Des Moines Des Moines Iowa United States 50316
    16 Hennepin County Medical Center Minneapolis Minnesota United States 55415
    17 Minneapolis VA Medical Center Minneapolis Minnesota United States 55417
    18 University of Minnesota Minneapolis Minnesota United States 55455
    19 Saint Luke's Hospital and Saint Luke's Cardiovascular Consultants Kansas City Missouri United States 64111
    20 AtlantiCare Health Network Egg Harbor Township New Jersey United States 08234
    21 New Mexico Heart Institute/Heart Hospital Albuquerque New Mexico United States 87102
    22 Asheville Cardiology Associates Asheville North Carolina United States 28803
    23 University of Cincinnati Cincinnati Ohio United States 45219
    24 MetroHealth Systems Cleveland Ohio United States 44109
    25 Cleveland Clinic Cleveland Ohio United States 44195
    26 The Ohio State University Columbus Ohio United States 43210
    27 Good Samaritan Hospital - Dayton Dayton Ohio United States 45415
    28 Oklahoma Heart Institute and Hillcrest Medical Center Tulsa Oklahoma United States 74104
    29 Abington Memorial Hospital Abington Pennsylvania United States 19001
    30 St. Luke's Hospital and Health Network Bethlehem Pennsylvania United States 18018
    31 Drexel University College of Medicine Philadelphia Pennsylvania United States 19102
    32 University of Pennsylvania Philadelphia Pennsylvania United States 19104
    33 Albert Einstein Medical Center Philadelphia Pennsylvania United States 19141
    34 Saint Thomas Hospital Nashville Tennessee United States 37205
    35 Brooke Army Medical Center San Antonio Texas United States 78234
    36 Virginia Commonwealth University Medical Center Richmond Virginia United States 23298
    37 MultiCare Health System/Tacoma General Hospital Tacoma Washington United States 98405
    38 Aurora St. Luke's Medical Center Milwaukee Wisconsin United States 53215

    Sponsors and Collaborators

    • Nuwellis, Inc.

    Investigators

    • Principal Investigator: Maria Rosa Costanzo, MD, Midwest Heart Foundation

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Nuwellis, Inc.
    ClinicalTrials.gov Identifier:
    NCT01474200
    Other Study ID Numbers:
    • 1494
    First Posted:
    Nov 18, 2011
    Last Update Posted:
    Jun 11, 2021
    Last Verified:
    Apr 1, 2017
    Keywords provided by Nuwellis, Inc.
    Ultrafiltration
    Aquapheresis
    Diuretics
    Loop Diuretics
    Aquadex Flexflow System
    Gambro UF Solutions
    Additional relevant MeSH terms:
    Heart Failure
    Furosemide
    Diuretics
    Sodium Potassium Chloride Symporter Inhibitors

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Period Title: Overall Study
    STARTED 110 114
    COMPLETED 81 84
    NOT COMPLETED 29 30

    Baseline Characteristics

    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD) Total
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol. Total of all reporting groups
    Overall Participants 110 111 221
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    67.03
    (12.61)
    66.87
    (13.45)
    66.95
    (13.01)
    Sex: Female, Male (Count of Participants)
    Female
    34
    30.9%
    30
    27%
    64
    29%
    Male
    76
    69.1%
    81
    73%
    157
    71%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    2
    1.8%
    3
    2.7%
    5
    2.3%
    Asian
    1
    0.9%
    3
    2.7%
    4
    1.8%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    31
    28.2%
    30
    27%
    61
    27.6%
    White
    75
    68.2%
    71
    64%
    146
    66.1%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    1
    0.9%
    4
    3.6%
    5
    2.3%
    Height (Centimeters) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Centimeters]
    172.45
    (11.04)
    174.12
    (10.52)
    173.29
    (10.79)
    Weight (Kilograms) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Kilograms]
    110.06
    (32.26)
    110.92
    (35.09)
    110.49
    (33.64)
    Body Mass Index (BMI) (Kg/m2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Kg/m2]
    36.89
    (10.13)
    36.32
    (10.10)
    36.61
    (10.10)

    Outcome Measures

    1. Primary Outcome
    Title Time to First Heart Failure (HF) Event
    Description 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
    Time Frame 90 days after discharge from index HF hospitalization.

    Outcome Measure Data

    Analysis Population Description
    Results reported are for the 25th percentile.
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 110 111
    Median (95% Confidence Interval) [Days]
    62
    34
    2. Secondary Outcome
    Title EFFICACY: Total Fluid Removed During the Index Hospitalization
    Description AQ-Fluid removed by AQ plus urine voided versus urine voided when treated with IV diuretics
    Time Frame Index Hospitalization, an average of 8 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 108 109
    Mean (Standard Deviation) [mL]
    18700
    (23033)
    14043
    (15299)
    3. Secondary Outcome
    Title EFFICACY: Net Fluid Removed During the Index Hospitalization
    Description AQ-Fluid removed by AQ plus urine voided minus fluid intake versus urine voided minus fluid intake with the IV diuretics.
    Time Frame Index Hospitalization, an average of 8 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 108 109
    Mean (Standard Deviation) [mL]
    12921
    (20564)
    8907
    (13329)
    4. Secondary Outcome
    Title EFFICACY: Weight Loss at 72 Hours After Initiation of Treatment
    Description Weight at 72 hours after treatment initiation minus weight at treatment initiation. Negative mean values indicate weight loss.
    Time Frame 72 hours after treatment initiation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 85 82
    Mean (Standard Deviation) [lbs]
    -10.69
    (7.20)
    -10.30
    (9.22)
    5. Secondary Outcome
    Title EFFICACY: Total Weight Loss During the Index Hospitalization
    Description Weight at hospital discharge minus weight at hospital admission. Negative mean values indicate weight loss.
    Time Frame Index Hospitalization, an average of 8 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 104 108
    Mean (Standard Deviation) [lbs]
    -17.12
    (12.59)
    -16.21
    (14.23)
    6. Secondary Outcome
    Title EFFICACY: Time to Freedom From Congestion
    Description 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.
    Time Frame Index Hospitalization, an average of 8 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 40 46
    Mean (Standard Deviation) [Days]
    5.28
    (4.11)
    3.86
    (3.23)
    7. Secondary Outcome
    Title EFFICACY: Freedom From Congestion
    Description 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
    Time Frame Index Hospitalization, an average of 8 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 110 111
    Number [Participants]
    40
    36.4%
    46
    41.4%
    8. Secondary Outcome
    Title EFFICACY: Changes in B-type Natriuretic Peptide (BNP) Levels Over Time
    Description Change in BNP levels over time at 72 hours, discharge, and 90 days after discharge.
    Time Frame Baseline and at 72 hours from baseline, hospital discharge and at 90 days after hospital discharge

    Outcome Measure Data

    Analysis Population Description
    Number of participants analyzed changes over time. Baseline: n=108 for AQ arm, n=109 for LD arm. 72 hours from baseline: n=81 for AQ arm, n=77 for LD arm. Discharge: n=83 for AQ arm, n=89 for LD arm. 90 days follow up: n=65 for AQ arm, n=76 for LD arm.
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 108 109
    Baseline
    814.0
    (827.66)
    904.1
    (843.44)
    72 hours from baseline
    -169.8
    (450.57)
    -120.5
    (469.04)
    Discharge
    -250.2
    (527.12)
    -219.1
    (539.26)
    90 days after discharge
    -159.9
    (678.20)
    -201.3
    (618.31)
    9. Secondary Outcome
    Title CLINICAL: Length of Stay (LOS) During the Index Hospitalization
    Description Number of days patient is in hospital for HF treatment.
    Time Frame Index hospitalization admission to index hospitalization discharge

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 105 108
    Mean (Standard Deviation) [Days]
    8.49
    (5.73)
    7.19
    (5.37)
    10. Secondary Outcome
    Title CLINICAL: Total Number of Days Rehospitalized for Heart Failure (HF) at 30 and 90 Days After Discharge
    Description 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.
    Time Frame Within 30 days and 90 days after hospital discharge

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 110 111
    30 days after discharge
    68
    172
    90 days after discharge
    338
    460
    11. Secondary Outcome
    Title CLINICAL: Total Number of Emergency Department (ED) or Unscheduled Office Visits at 30 and 90 Days After Discharge
    Description Number of visits for HF symptoms requiring ED or clinic treatment involving the use of IV diuretics and /or positive inotropic or vasodilator drugs
    Time Frame Within 30 days and 90 days after hospital discharge

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 110 111
    30 days after discharge
    4
    5
    90 days after discharge
    7
    8
    12. Secondary Outcome
    Title CLINICAL: Total Number of Heart Failure (HF) Rehospitalizations at 30 and 90 Days After Discharge
    Description Number of different times patient was admitted to hospital for HF symptoms within 90 days of index hospitalization discharge.
    Time Frame Within 30 days and 90 days after hospital discharge

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 110 111
    30 days after discharge
    11
    24
    90 days after discharge
    36
    52
    13. Secondary Outcome
    Title CLINICAL: Total Number of Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge
    Description CV symptoms that required hospitalization for treatment within 90 days of index hospitalization discharge.
    Time Frame Within 30 days and 90 days after hospital discharge

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 110 111
    30 days after discharge
    17
    33
    90 days after discharge
    46
    66
    14. Secondary Outcome
    Title CLINICAL: Total Number of Days for Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge
    Description The total number of days spent in the hospital due to CV related events at 30 days and 90 days from hospital discharge.
    Time Frame Within 30 days and 90 days after hospital discharge

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 110 111
    30 days after discharge
    88
    207
    90 days after discharge
    377
    554
    15. Secondary Outcome
    Title CLINICAL: All Cause Rehospitalization Rates at 30 and 90 Days
    Description Any cause that required hospitalization for treatment within 90 days of index hospitalization discharge.
    Time Frame Within 30 days and 90 days after hospital discharge

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 110 111
    30 days after discharge
    0.899
    1.278
    90 days after discharge
    1.109
    1.237
    16. Secondary Outcome
    Title CLINICAL: Mortality Rates Within Index Hospitalization or Within 90 Days After Hospital Discharge.
    Description Death due to any cause.
    Time Frame Time from randomization to 90 days post-hospital discharge

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 110 111
    Number [Percentage of Participants]
    15.45
    14%
    12.61
    11.4%
    17. Secondary Outcome
    Title CLINICAL: Days Alive and Out of Hospital at 30 and 90 Days After Discharge
    Description Number of days patients were alive and out of the hospital.
    Time Frame Within 30 and 90 days after hospital discharge

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 105 108
    30 days after discharge
    27.29
    (5.78)
    26.46
    (6.34)
    90 days after discharge
    62
    (24.57)
    61.38
    (24.95)
    18. Secondary Outcome
    Title CLINICAL: Quality of Life Assessed Using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 30, 60 and 90 Days After Discharge
    Description 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.
    Time Frame Within 90 days after hospital discharge

    Outcome Measure Data

    Analysis Population Description
    Number of participants analyzed changes over time. Baseline: n=107 for AQ arm, n=110 for LD arm. 30 day follow up: n=85 for AQ arm, n=91 for LD arm. 90 day follow up: n=72 for AQ arm, n=77 for LD arm.
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 107 110
    Baseline
    25.39
    (19.37)
    28.64
    (22.59)
    30 days after discharge
    52.06
    (28.58)
    49.36
    (28.82)
    90 days after discharge
    59.72
    (24.90)
    58.50
    (26.72)
    19. Secondary Outcome
    Title CLINICAL: Global Clinical Score at 30 and 90 Days After Discharge
    Description 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.
    Time Frame Within 90 days after hospital discharge

    Outcome Measure Data

    Analysis Population Description
    Number of participants analyzed changes over time. Baseline: n=107 for AQ arm, n=110 for LD arm. 30 day follow up: n=85 for AQ arm, n=92 for LD arm. 90 day follow up: n=72 for AQ arm, n=77 for LD arm.
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 107 110
    Baseline
    28.26
    (18.65)
    31.83
    (18.63)
    30 days after discharge
    54.78
    (24.15)
    53.08
    (26.01)
    90 days after discharge
    57.21
    (25.39)
    60.56
    (26.34)
    20. Secondary Outcome
    Title SAFETY: Changes in Renal Function (Serum Creatinine) After Treatment up to 90 Days After Randomization
    Description 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
    Time Frame Within 90 days of randomization

    Outcome Measure Data

    Analysis Population Description
    Number of participants analyzed changes over time. Discharge: n=105 for AQ arm, n=108 for LD arm. 30 days after discharge: n=93 for AQ arm, n=95 for LD arm. 60 days after discharge: n=85 for AQ arm, n=84 for LD arm. 90 days after discharge: n=4 for AQ arm, n=6 for LD arm.
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 105 108
    Discharge
    0.12
    (0.42)
    0.12
    (0.50)
    30 days after discharge
    0.37
    (3.41)
    0.17
    (0.63)
    60 days after discharge
    1.34
    (11.40)
    -0.01
    (0.44)
    90 days after discharge
    -0.30
    (0.42)
    -0.24
    (0.30)
    21. Secondary Outcome
    Title SAFETY: Changes in Renal Function (Blood Urea Nitrogen) After Treatment up to 90 Days After Randomization
    Description 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
    Time Frame Within 90 days of randomization

    Outcome Measure Data

    Analysis Population Description
    Number of participants analyzed changes over time. Baseline: n=105 for AQ arm, n=108 for LD arm. 30 days after discharge: n=93 for AQ arm, n=95 for LD arm. 60 days after discharge: n=85 for AQ arm, n=84 for LD arm. 90 days after discharge: n=4 for AQ arm, n=6 for LD arm.
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 105 108
    Discharge
    8.38
    (13.94)
    7.62
    (14.34)
    30 days after discharge
    1.72
    (14.44)
    6.56
    (22.80)
    60 days after discharge
    1.85
    (16.62)
    3.16
    (17.78)
    90 days after discharge
    2.50
    (6.36)
    -3.78
    (4.19)
    22. Secondary Outcome
    Title SAFETY: Changes in Renal Function (Blood Urea Nitrogen/Serum Creatinine) After Treatment up to 90 Days After Randomization
    Description 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
    Time Frame Within 90 days of randomization

    Outcome Measure Data

    Analysis Population Description
    Number of participants analyzed changes over time. Discharge: n=105 for AQ arm, n=108 for LD arm. 30 days after discharge: n=93 for AQ arm, n=95 for LD arm. 60 days after discharge: n=85 for AQ arm, n=84 for LD arm. 90 days after discharge: n=4 for AQ arm, n=6 for LD arm.
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 105 108
    Discharge
    3.77
    (7.80)
    3.03
    (6.52)
    30 days after discharge
    0.28
    (6.88)
    1.65
    (8.85)
    60 days after discharge
    0.07
    (7.07)
    1.97
    (7.42)
    90 days after discharge
    5.66
    (1.40)
    1.72
    (5.56)
    23. Secondary Outcome
    Title SAFETY: Changes in Renal Function (Estimated Glomerular Filtration Rate) After Treatment up to 90 Days After Randomization
    Description 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
    Time Frame Within 90 days of randomization

    Outcome Measure Data

    Analysis Population Description
    Number of participants analyzed changes over time. Discharge: n=105 for AQ arm, n=108 for LD arm. 30 days after discharge: n=93 for AQ arm, n=95 for LD arm. 60 days after discharge: n=85 for AQ arm, n=84 for LD arm. 90 days after discharge: n=4 for AQ arm, n=6 for LD arm.
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    Measure Participants 105 108
    Discharge
    -2.31
    (14.50)
    -2.68
    (13.45)
    30 days after discharge
    -0.56
    (14.24)
    -3.33
    (14.97)
    60 days after discharge
    -2.49
    (16.81)
    2.15
    (13.79)
    90 days after discharge
    5.70
    (8.06)
    7.41
    (11.87)

    Adverse Events

    Time Frame Baseline through 90 days after discharge.
    Adverse Event Reporting Description
    Arm/Group Title Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Arm/Group Description Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol.
    All Cause Mortality
    Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 73/110 (66.4%) 67/111 (60.4%)
    Cardiac disorders
    Cardiac Failure 5/110 (4.5%) 8/111 (7.2%)
    Cardiac Failure Acute 13/110 (11.8%) 19/111 (17.1%)
    Cardiac Failure Congestive 11/110 (10%) 20/111 (18%)
    Acute Coronary Syndrom 1/110 (0.9%) 0/111 (0%)
    Acute Myocardial Infarction 1/110 (0.9%) 0/111 (0%)
    Arrhythmia 1/110 (0.9%) 0/111 (0%)
    Atrial Fibrillation 3/110 (2.7%) 2/111 (1.8%)
    Atrioventricular Block Second Degree 1/110 (0.9%) 0/111 (0%)
    Cardiac Arrest 3/110 (2.7%) 2/111 (1.8%)
    Cardiac Failure Chronic 2/110 (1.8%) 3/111 (2.7%)
    Cardio-Respiratory Arrest 2/110 (1.8%) 1/111 (0.9%)
    Cardiogenic Shock 1/110 (0.9%) 0/111 (0%)
    Cardiomyopathy 1/110 (0.9%) 1/111 (0.9%)
    Cardiorenal Syndrome 0/110 (0%) 1/111 (0.9%)
    Cardiovascular Insufficiency 1/110 (0.9%) 0/111 (0%)
    Congestive Cardiomyopathy 1/110 (0.9%) 0/111 (0%)
    Cor Pulmonale 0/110 (0%) 2/111 (1.8%)
    Ischaemic Cardiomyopathy 0/110 (0%) 1/111 (0.9%)
    Myocardial Infarction 1/110 (0.9%) 0/111 (0%)
    Palpitations 1/110 (0.9%) 0/111 (0%)
    Right Ventricular Failure 0/110 (0%) 1/111 (0.9%)
    Supra Ventricular Tachycardia 0/110 (0%) 1/111 (0.9%)
    Ventricular Tachycardia 2/110 (1.8%) 0/111 (0%)
    Gastrointestinal disorders
    Abdominal Pain Lower 0/110 (0%) 1/111 (0.9%)
    Abdominal Pain Upper 0/110 (0%) 1/111 (0.9%)
    Abdominal Wall Haematoma 1/110 (0.9%) 0/111 (0%)
    Gastric Antral Vascular Ectasia 1/110 (0.9%) 0/111 (0%)
    Gastrointestinal Haemorrhage 2/110 (1.8%) 1/111 (0.9%)
    Lower Gastrointestinal Haemorrhage 1/110 (0.9%) 0/111 (0%)
    Pancreatitis 1/110 (0.9%) 0/111 (0%)
    Upper Gastrointestinal Haemorrhage 0/110 (0%) 1/111 (0.9%)
    General disorders
    Chest Pain 4/110 (3.6%) 1/111 (0.9%)
    Cardiac Death 0/110 (0%) 1/111 (0.9%)
    Chest Discomfort 1/110 (0.9%) 0/111 (0%)
    Death 0/110 (0%) 3/111 (2.7%)
    Device Lead Issue 0/110 (0%) 1/111 (0.9%)
    Malaise 1/110 (0.9%) 0/111 (0%)
    Medical Device Complication 0/110 (0%) 1/111 (0.9%)
    Non-Cardiac Chest Pain 1/110 (0.9%) 1/111 (0.9%)
    Pain 0/110 (0%) 1/111 (0.9%)
    Pyrexia 1/110 (0.9%) 0/111 (0%)
    Hepatobiliary disorders
    Gallbladder Perforation 0/110 (0%) 1/111 (0.9%)
    Immune system disorders
    Sarcoidosis 1/110 (0.9%) 0/111 (0%)
    Infections and infestations
    Pneumonia 5/110 (4.5%) 0/111 (0%)
    Cellulitis 2/110 (1.8%) 2/111 (1.8%)
    Filariasis 1/110 (0.9%) 0/111 (0%)
    Infection 2/110 (1.8%) 0/111 (0%)
    Sepsis 1/110 (0.9%) 1/111 (0.9%)
    Septic Shock 0/110 (0%) 1/111 (0.9%)
    Staphylococcal Infection 1/110 (0.9%) 0/111 (0%)
    Upper Respiratory Tract Infection 2/110 (1.8%) 0/111 (0%)
    Urinary Tract Infection 0/110 (0%) 1/111 (0.9%)
    Wound Infection 1/110 (0.9%) 0/111 (0%)
    Injury, poisoning and procedural complications
    Hip Fracture 1/110 (0.9%) 0/111 (0%)
    Procedural Haemorrhage 1/110 (0.9%) 0/111 (0%)
    Renal Haematoma 1/110 (0.9%) 0/111 (0%)
    Spinal Compression Fracture 1/110 (0.9%) 0/111 (0%)
    Vascular Graft Thrombosis 1/110 (0.9%) 0/111 (0%)
    Investigations
    Blood Creatinine Increase 4/110 (3.6%) 0/111 (0%)
    Anticoagulation Drug Level Below Therapeautic 1/110 (0.9%) 0/111 (0%)
    Cardiac Output Decreased 1/110 (0.9%) 0/111 (0%)
    Haematocrit Decreased 1/110 (0.9%) 0/111 (0%)
    International Normalised Ratio Increased 1/110 (0.9%) 0/111 (0%)
    Metabolism and nutrition disorders
    Dehydration 1/110 (0.9%) 0/111 (0%)
    Fluid Overload 1/110 (0.9%) 3/111 (2.7%)
    Hyperkalaemia 1/110 (0.9%) 0/111 (0%)
    Hypoglycaemia 1/110 (0.9%) 0/111 (0%)
    Musculoskeletal and connective tissue disorders
    Back Pain 0/110 (0%) 1/111 (0.9%)
    Cervical Spinal Stenosis 1/110 (0.9%) 0/111 (0%)
    Nervous system disorders
    Cerebrovascular Accident 1/110 (0.9%) 1/111 (0.9%)
    Cerebrovascular Disorder 0/110 (0%) 1/111 (0.9%)
    Encephalopathy 0/110 (0%) 1/111 (0.9%)
    Headache 0/110 (0%) 1/111 (0.9%)
    Neurological Symptom 2/110 (1.8%) 1/111 (0.9%)
    Neuropathy Peripheral 1/110 (0.9%) 0/111 (0%)
    Presyncope 0/110 (0%) 1/111 (0.9%)
    Syncope 2/110 (1.8%) 1/111 (0.9%)
    Transient Ischaemic Attack 0/110 (0%) 1/111 (0.9%)
    Psychiatric disorders
    Confusional State 1/110 (0.9%) 0/111 (0%)
    Depression 1/110 (0.9%) 0/111 (0%)
    Renal and urinary disorders
    Renal Failure Acute 4/110 (3.6%) 3/111 (2.7%)
    Haematuria 1/110 (0.9%) 0/111 (0%)
    Renal Failure 1/110 (0.9%) 0/111 (0%)
    Renal Failure Chronic 2/110 (1.8%) 0/111 (0%)
    Renal Impairment 1/110 (0.9%) 0/111 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute Respiratory Failure 1/110 (0.9%) 1/111 (0.9%)
    Chronic Respiratory Failure 0/110 (0%) 1/111 (0.9%)
    Dyspnoea 3/110 (2.7%) 0/111 (0%)
    Hypoxia 0/110 (0%) 1/111 (0.9%)
    Pickwickian Syndrome 0/110 (0%) 1/111 (0.9%)
    Pleural Effusion 1/110 (0.9%) 1/111 (0.9%)
    Pulmonary Hypertension 0/110 (0%) 1/111 (0.9%)
    Respiratory Distress 0/110 (0%) 1/111 (0.9%)
    Surgical and medical procedures
    Cardiac Ablation 0/110 (0%) 1/111 (0.9%)
    Cardioversion 1/110 (0.9%) 2/111 (1.8%)
    Implantable Defibrillator Insertion 3/110 (2.7%) 0/111 (0%)
    Ventricular Assist Device Insertion 0/110 (0%) 1/111 (0.9%)
    Vascular disorders
    Hypotension 3/110 (2.7%) 5/111 (4.5%)
    Deep Vein Thrombosis 1/110 (0.9%) 1/111 (0.9%)
    Hypertensive Crisis 0/110 (0%) 1/111 (0.9%)
    Orthostatic Hypotension 0/110 (0%) 1/111 (0.9%)
    Other (Not Including Serious) Adverse Events
    Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration IV Loop Diuretics (LD)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 25/110 (22.7%) 18/111 (16.2%)
    Infections and infestations
    Urinary Tract Infection 3/110 (2.7%) 7/111 (6.3%)
    Investigations
    Blood Creatinine Increase 7/110 (6.4%) 4/111 (3.6%)
    Metabolism and nutrition disorders
    Hyperkalaemia 8/110 (7.3%) 4/111 (3.6%)
    Renal and urinary disorders
    Renal Failure Acute 5/110 (4.5%) 7/111 (6.3%)
    Vascular disorders
    Hypotension 12/110 (10.9%) 7/111 (6.3%)

    Limitations/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.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Results Point of Contact

    Name/Title Drew Jones, MD, Senior Medical Director
    Organization Baxter Healthcare Corporation
    Phone 224-270-2659
    Email drew_jones@baxter.com
    Responsible Party:
    Nuwellis, Inc.
    ClinicalTrials.gov Identifier:
    NCT01474200
    Other Study ID Numbers:
    • 1494
    First Posted:
    Nov 18, 2011
    Last Update Posted:
    Jun 11, 2021
    Last Verified:
    Apr 1, 2017