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

Not Applicable

Terminated

Conditions: Heart Failure
Acute Decompensated Heart Failure (ADHF)
Cardiac Failure

Interventions: Drug: IV Loop Diuretics (LD)
Device: Isolated veno-venous ultrafiltration (AQ)

Registration Number: NCT01474200

Lead Sponsor: Nuwellis, Inc.

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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 224

Inclusion Criteria

18 years of age or older
Male or non-pregnant female patients
Admitted to the hospital with a primary diagnosis of acute decompensated heart failure (ADHF)
On regularly scheduled oral loop diuretics prior to admission
Fluid overload manifested by at least two of the following:
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.
Have received ≤ 2 IV loop diuretics doses before randomization
Must be able to be enrolled into the trial ≤ 24 hours of their admission to the hospital.
Provide written informed consent form as required by the local IRB (Institutional Review Board)

Exclusion Criteria

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IV Loop Diuretics (LD)	IV Loop Diuretics (LD)	Excess fluid from the patient is removed by IV (Intravenous) loop diuretic treatment
Aquapheresis (AQ) - isolated veno-venous ultrafiltration	Isolated veno-venous ultrafiltration (AQ)	Excess fluid from the patient is removed by isolated veno-venous ultrafiltration treatment using the Aquadex Flex Flow System

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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
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.
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.
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.
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
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.
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
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
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
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.
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.
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
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.
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.
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.
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 at 30 and 90 days after discharge.
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.
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 within index hospitalization and 90 days following hospital discharge.
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
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.
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.

Trial Locations

Locations (38): Elkhart General HealthCare
🇺🇸
Elkhart, Indiana, United States
Drexel University College of Medicine
🇺🇸
Philadelphia, Pennsylvania, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
The Ohio State University
🇺🇸
Columbus, Ohio, United States
Morton Plant Medical Center
🇺🇸
Clearwater, Florida, United States
University of California, San Diego (UCSD)
🇺🇸
San Diego, California, United States
MetroHealth Systems
🇺🇸
Cleveland, Ohio, United States
Mayo Clinic - Scottsdale
🇺🇸
Scottsdale, Arizona, United States
Scottsdale Healthcare Research Institute
🇺🇸
Scottsdale, Arizona, United States
AtlantiCare Health Network
🇺🇸
Egg Harbor Township, New Jersey, United States
University of Minnesota
🇺🇸
Minneapolis, Minnesota, United States
Brooke Army Medical Center
🇺🇸
San Antonio, Texas, United States
Hennepin County Medical Center
🇺🇸
Minneapolis, Minnesota, United States
Minneapolis VA Medical Center
🇺🇸
Minneapolis, Minnesota, United States
Saint Thomas Hospital
🇺🇸
Nashville, Tennessee, United States
Aurora St. Luke's Medical Center
🇺🇸
Milwaukee, Wisconsin, United States
Heart Center Research
🇺🇸
Huntsville, Alabama, United States
UCLA
🇺🇸
Los Angeles, California, United States
San Diego Cardiac Center
🇺🇸
San Diego, California, United States
Washington Hospital Center
🇺🇸
Washington, District of Columbia, United States
Emory University
🇺🇸
Atlanta, Georgia, United States
Edward Hospital Center for Advanced Heart Failure
🇺🇸
Naperville, Illinois, United States
Advocate Health & Hospitals Corporation
🇺🇸
Oakbrook Terrace, Illinois, United States
Northern Indiana Research Alliance
🇺🇸
Fort Wayne, Indiana, United States
Iowa Health - Des Moines
🇺🇸
Des Moines, Iowa, United States
New Mexico Heart Institute/Heart Hospital
🇺🇸
Albuquerque, New Mexico, United States
Asheville Cardiology Associates
🇺🇸
Asheville, North Carolina, United States
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
Oklahoma Heart Institute and Hillcrest Medical Center
🇺🇸
Tulsa, Oklahoma, United States
Good Samaritan Hospital - Dayton
🇺🇸
Dayton, Ohio, United States
Abington Memorial Hospital
🇺🇸
Abington, Pennsylvania, United States
St. Luke's Hospital and Health Network
🇺🇸
Bethlehem, Pennsylvania, United States
Albert Einstein Medical Center
🇺🇸
Philadelphia, Pennsylvania, United States
MultiCare Health System/Tacoma General Hospital
🇺🇸
Tacoma, Washington, United States
Northwestern University
🇺🇸
Evanston, Illinois, United States
Saint Luke's Hospital and Saint Luke's Cardiovascular Consultants
🇺🇸
Kansas City, Missouri, United States
Virginia Commonwealth University Medical Center
🇺🇸
Richmond, Virginia, United States