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

August 3, 2023 updated by: Nuwellis, Inc.

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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
224

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Time to First Heart Failure (HF) Event
Time Frame: 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
90 days after discharge from index HF hospitalization.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
EFFICACY: Total Fluid Removed During the Index Hospitalization
Time Frame: Index Hospitalization, an average of 8 days
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
Time Frame: 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.
Index Hospitalization, an average of 8 days
EFFICACY: Weight Loss at 72 Hours After Initiation of Treatment
Time Frame: 72 hours after treatment initiation
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
Time Frame: Index Hospitalization, an average of 8 days
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 Frame: 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.
Index Hospitalization, an average of 8 days
EFFICACY: Freedom From Congestion
Time Frame: 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
Index Hospitalization, an average of 8 days
EFFICACY: Changes in B-type Natriuretic Peptide (BNP) Levels Over Time
Time Frame: 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.
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
Time Frame: 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.
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
Time Frame: 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
Within 30 days and 90 days after hospital discharge
CLINICAL: Total Number of Heart Failure (HF) Rehospitalizations at 30 and 90 Days After Discharge
Time Frame: 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.
Within 30 days and 90 days after hospital discharge
CLINICAL: Total Number of Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge
Time Frame: Within 30 days and 90 days after hospital 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
Time Frame: 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.
Within 30 days and 90 days after hospital discharge
CLINICAL: All Cause Rehospitalization Rates at 30 and 90 Days
Time Frame: Within 30 days and 90 days after hospital discharge
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
Time Frame: 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.
Within 90 days after hospital discharge
SAFETY: Changes in Renal Function (Serum Creatinine) After Treatment up to 90 Days After Randomization
Time Frame: 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
Within 90 days of randomization
SAFETY: Changes in Renal Function (Blood Urea Nitrogen) After Treatment up to 90 Days After Randomization
Time Frame: 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
Within 90 days of randomization
SAFETY: Changes in Renal Function (Blood Urea Nitrogen/Serum Creatinine) After Treatment up to 90 Days After Randomization
Time Frame: 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
Within 90 days of randomization
SAFETY: Changes in Renal Function (Estimated Glomerular Filtration Rate) After Treatment up to 90 Days After Randomization
Time Frame: 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
Within 90 days of randomization
Length of Stay (LOS) During the Index Hospitalization
Time Frame: Index hospitalization admission to index hospitalization discharge
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.
Time Frame: Time from randomization to 90 days post-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
Time Frame: Within 30 and 90 days after hospital 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
Time Frame: 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.
Within 90 days after hospital discharge

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Nuwellis, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Maria Rosa Costanzo, MD, Midwest Heart Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 11, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 15, 2011

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 18, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 29, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 3, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1494 (CSL Behring)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings