Title
Study of Heart Failure Hospitalizations After Aquapheresis Therapy Compared to Intravenous (IV) Diuretic Treatment
Aquapheresis Versus Intravenous Diuretics and Hospitalizations for Heart Failure (AVOID-HF)
Phase
N/ALead Sponsor
BaxaltaStudy Type
InterventionalStatus
Terminated Results PostedIndication/Condition
Acute Decompensated Heart Failure (ADHF) ...Intervention/Treatment
furosemide ...Study Participants
224The 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.
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.
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)
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.
Excess fluid from the patient is removed by isolated veno-venous ultrafiltration treatment using the Aquadex Flex Flow System
Excess fluid from the patient is removed by IV (Intravenous) loop diuretic treatment
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
| Event Type | Organ System | Event Term | Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | IV Loop Diuretics (LD) |
|---|
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
AQ-Fluid removed by AQ plus urine voided versus urine voided when treated with IV diuretics
AQ-Fluid removed by AQ plus urine voided minus fluid intake versus urine voided minus fluid intake with the IV diuretics.
Weight at 72 hours after treatment initiation minus weight at treatment initiation. Negative mean values indicate weight loss.
Weight at hospital discharge minus weight at hospital admission. Negative mean values indicate weight loss.
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.
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
Change in BNP levels over time at 72 hours, discharge, and 90 days after discharge.
Number of days patient is in hospital for HF treatment.
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.
Number of visits for HF symptoms requiring ED or clinic treatment involving the use of IV diuretics and /or positive inotropic or vasodilator drugs
Number of different times patient was admitted to hospital for HF symptoms within 90 days of index hospitalization discharge.
CV symptoms that required hospitalization for treatment within 90 days of index hospitalization discharge.
The total number of days spent in the hospital due to CV related events at 30 days and 90 days from hospital discharge.
Any cause that required hospitalization for treatment within 90 days of index hospitalization discharge.
Death due to any cause within index hospitalization and 90 days following hospital discharge.
Number of days patients were alive and out of the hospital at 30 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.
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.
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
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
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
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
