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

Nuwellis, Inc.224 enrolled

Overview

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.

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

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

224

Conditions

Heart Failure Cardiac Failure Acute Decompensated Heart Failure (ADHF)

Interventions

Isolated veno-venous ultrafiltration (AQ)DEVICE

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 (LD)DRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (38)

Outcomes

Primary Outcomes

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

Time frame: 90 days after discharge from index HF hospitalization.

Secondary Outcomes

EFFICACY: Total Fluid Removed During the Index Hospitalization

AQ-Fluid removed by AQ plus urine voided versus urine voided when treated with IV diuretics

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.