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

Study Overview
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Brief Summary
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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
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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.

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

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

Intervention / Treatment
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* Device: Isolated veno-venous ultrafiltration (AQ)
* Drug: IV Loop Diuretics (LD)


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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aquapheresis (AQ) - isolated veno-venous ultrafiltration<br>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)<br>* 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)<br>* Other names: Gambro UF Solutions;|
| Active Comparator: IV Loop Diuretics (LD)<br>Excess fluid from the patient is removed by IV (Intravenous) loop diuretic treatment | Drug: IV Loop Diuretics (LD)<br>* 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 theDiuretic strategies in patients wth acute decompensated heart failure (DOSE) trial.<br>* Other names: furosemide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Heart Failure (HF) Event | Time to first HF event within 90 days after discharge from index HF hospitalization. HF events are defined as HF rehospitalization or unscheduled outpatient or emergency room treatment with IV loop diuretics or unscheduled outpatient Aquapheresis treatment | 90 days after discharge from index HF hospitalization. | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ultrafiltration, Aquapheresis, Diuretics, Loop Diuretics, Aquadex Flexflow System, Gambro UF Solutions