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

• Time to first HF event [ Time Frame: 90 days after discharge from index HF hospitalization. ] [ Designated as safety issue: No ]

  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
  
  

• EFFICACY: Total fluid removed during the index hospitalization [ Time Frame: Participants will be followed for the duration of the index hospitalization, an expected average of 6 days ] [ Designated as safety issue: No ]
  AQ-Fluid removed by AQ plus urine voided versus urine voided when treated with IV diuretics
  
  
• EFFICACY: Net fluid removed during the index hospitalization [ Time Frame: Participants will be followed for the duration of the index hospitalization, an expected average of 6 days ] [ Designated as safety issue: No ]
  AQ-Fluid removed by AQ plus urine voided minus fluid intake versus urine voided minus fluid intake with the IV diuretics.
  
  
• EFFICACY: Weight loss at 72 hours after initiation of treatment [ Time Frame: 72 hours after treatment initiation ] [ Designated as safety issue: No ]
  Weight at 72 hours after treatment initiation minus weight at treatment initiation.
  
  
• EFFICACY: Total weight loss during the index hospitalization [ Time Frame: Participants will be followed for the duration of the index hospitalization, an expected average of 6 days ] [ Designated as safety issue: No ]
  Weight at hospital discharge minus weight at hospital admission
  
  
• EFFICACY: Time to freedom from congestion [ Time Frame: Participants will be followed for the duration of the index hospitalization, an expected average of 6 days ] [ Designated as safety issue: No ]
  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 [ Time Frame: Participants will be followed for the duration of index hospitalization, an expected average of 6 days ] [ Designated as safety issue: No ]
  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
  
  
• EFFICACY: Changes in B-type natriuretic peptide (BNP) levels over time [ Time Frame: At 72 hours from baseline, at hospital discharge, at 30 days, 60 days and 90 days after hospital discharge ] [ Designated as safety issue: No ]
  Blood tests to determine level of BNP at prescribed intervals.
  
  
• CLINICAL: Length of stay (LOS) during the index hospitalization [ Time Frame: Duration from index hospitalization admission to index hospitalization discharge, an expected average of 6 days ] [ Designated as safety issue: No ]
  Number of days patient is in hospital for HF treatment.
  
  
• CLINICAL: Total number of days rehospitalized for Heart Failure (HF) at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
  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 Emergency Department (ED) or unscheduled office visits at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
  HF symptoms requiring hospital, ED 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 [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
  Number of different times patient iS admitted to hospital for HF symptoms within 90 days of index hospitalization discharge.
  
  
• CLINICAL: Total number of cardiovascular (CV) rehospitalizations at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
  CV symptoms that require hospitalization for treatment within 90 days of index hospitalization discharge.
  
  
• CLINICAL: Total number of days for cardiovascular (CV) rehospitalizations at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
  
• CLINICAL: All cause rehospitalization rates at 30 and 90 days [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
  Any cause that requires hospitalization for treatment within 90 days of index hospitalization discharge.
  
  
• CLINICAL: Mortality rates within index hospitalization or within 90 days after hospital discharge. [ Time Frame: Time from randomization to 90 days post-hospital discharge ] [ Designated as safety issue: No ]
  Death due to any cause.
  
  
• CLINICAL: Days alive and out of hospital at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
  Death due to any cause post-hospital discharge.
  
  
• CLINICAL: 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 ] [ Designated as safety issue: No ]
  Questionnaire assessing patients quality of life prior to index treatment versus timeframes following hospital discharge.
  
  
• CLINICAL: Global clinical score at 30 and 90 days after discharge [ Time Frame: Within 90 days after hospital discharge ] [ Designated as safety issue: No ]
  Patient's self assessment of how they feel at various intervals compared to how they felt prior to index treatment.
  
  
• SAFETY: Changes in renal function variables after treatment up to 90 days after randomization [ Time Frame: Within 90 days of randomization ] [ Designated as safety issue: Yes ]
  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
  
  

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.