Acute Decompensated Heart Failure (ADHF), Cardiac Failure, Heart Failure
Conditions
Keywords
Ultrafiltration, Aquapheresis, Diuretics, Loop Diuretics, Aquadex Flexflow System, Gambro UF Solutions
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.
Interventions
DEVICEIsolated veno-venous ultrafiltration (AQ)
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)
DRUGIV Loop Diuretics (LD)
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.
Sponsors
Nuwellis, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: 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. |
| 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 |
| 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. |
| 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 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 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 |
| 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. |
| 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 |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 (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 |
| 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 |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration Excess fluid from the patient was removed by isolated veno-venous ultrafiltration treatment using the FDA cleared Aquadex Flex Flow System during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. Diuretics were withheld for the duration of the AQ treatment and the use of positive inotropic agents and vasodilators were prohibited unless deemed necessary by the treating physician as rescue therapy. Ultrafiltration rates and monitoring of treatment were outlined in treatment guidelines. | 110 |
| IV Loop Diuretics (LD) Excess fluid from the patient was removed by IV (Intravenous) loop diuretic treatment using only FDA approved IV loop diuretics indicated for the treatment of patients with fluid overload during index hospitalization until the patient's signs and symptoms of fluid overload improved to the satisfaction of the treating physician. This included furosemide or other IV loop diuretics administered at equivalent doses to furosemide. The recommended doses of IV bolus, maintenance dose and potential additional diuretics were outlined in treatment guidelines and were based on the CARRESS-HF Stepped Pharmacologic Protocol. | 111 |
| Total | 221 |
Baseline characteristics
| Characteristic | Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | IV Loop Diuretics (LD) | Total |
|---|---|---|---|
| Age, Continuous | 67.03 Years STANDARD_DEVIATION 12.61 | 66.87 Years STANDARD_DEVIATION 13.45 | 66.95 Years STANDARD_DEVIATION 13.01 |
| Body Mass Index (BMI) | 36.89 Kg/m2 STANDARD_DEVIATION 10.13 | 36.32 Kg/m2 STANDARD_DEVIATION 10.1 | 36.61 Kg/m2 STANDARD_DEVIATION 10.1 |
| Height | 172.45 Centimeters STANDARD_DEVIATION 11.04 | 174.12 Centimeters STANDARD_DEVIATION 10.52 | 173.29 Centimeters STANDARD_DEVIATION 10.79 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 31 Participants | 30 Participants | 61 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) White | 75 Participants | 71 Participants | 146 Participants |
| Sex: Female, Male Female | 34 Participants | 30 Participants | 64 Participants |
| Sex: Female, Male Male | 76 Participants | 81 Participants | 157 Participants |
| Weight | 110.06 Kilograms STANDARD_DEVIATION 32.26 | 110.92 Kilograms STANDARD_DEVIATION 35.09 | 110.49 Kilograms STANDARD_DEVIATION 33.64 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 25 / 110 | 18 / 111 |
| serious Total, serious adverse events | 73 / 110 | 67 / 111 |
Outcome results
Primary
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.
Population: Results reported are for the 25th percentile.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | Time to First Heart Failure (HF) Event | 62 Days |
| IV Loop Diuretics (LD) | Time to First Heart Failure (HF) Event | 34 Days |
Secondary
CLINICAL: All Cause Rehospitalization Rates at 30 and 90 Days
Any cause that required hospitalization for treatment within 90 days of index hospitalization discharge.
Time frame: Within 30 days and 90 days after hospital discharge
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | CLINICAL: All Cause Rehospitalization Rates at 30 and 90 Days | 30 days after discharge | 0.899 Rehospitalizations/100 Pt-Days at Risk |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | CLINICAL: All Cause Rehospitalization Rates at 30 and 90 Days | 90 days after discharge | 1.109 Rehospitalizations/100 Pt-Days at Risk |
| IV Loop Diuretics (LD) | CLINICAL: All Cause Rehospitalization Rates at 30 and 90 Days | 30 days after discharge | 1.278 Rehospitalizations/100 Pt-Days at Risk |
| IV Loop Diuretics (LD) | CLINICAL: All Cause Rehospitalization Rates at 30 and 90 Days | 90 days after discharge | 1.237 Rehospitalizations/100 Pt-Days at Risk |
Secondary
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.
Time frame: Within 90 days after hospital discharge
Population: Number of participants analyzed changes over time. Baseline: n=107 for AQ arm, n=110 for LD arm. 30 day follow up: n=85 for AQ arm, n=92 for LD arm. 90 day follow up: n=72 for AQ arm, n=77 for LD arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | CLINICAL: Global Clinical Score at 30 and 90 Days After Discharge | Baseline | 28.26 Scores on a Scale | Standard Deviation 18.65 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | CLINICAL: Global Clinical Score at 30 and 90 Days After Discharge | 30 days after discharge | 54.78 Scores on a Scale | Standard Deviation 24.15 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | CLINICAL: Global Clinical Score at 30 and 90 Days After Discharge | 90 days after discharge | 57.21 Scores on a Scale | Standard Deviation 25.39 |
| IV Loop Diuretics (LD) | CLINICAL: Global Clinical Score at 30 and 90 Days After Discharge | Baseline | 31.83 Scores on a Scale | Standard Deviation 18.63 |
| IV Loop Diuretics (LD) | CLINICAL: Global Clinical Score at 30 and 90 Days After Discharge | 30 days after discharge | 53.08 Scores on a Scale | Standard Deviation 26.01 |
| IV Loop Diuretics (LD) | CLINICAL: Global Clinical Score at 30 and 90 Days After Discharge | 90 days after discharge | 60.56 Scores on a Scale | Standard Deviation 26.34 |
Secondary
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.
Time frame: Within 30 days and 90 days after hospital discharge
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | CLINICAL: Total Number of Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge | 30 days after discharge | 17 Rehospitalizations |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | CLINICAL: Total Number of Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge | 90 days after discharge | 46 Rehospitalizations |
| IV Loop Diuretics (LD) | CLINICAL: Total Number of Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge | 30 days after discharge | 33 Rehospitalizations |
| IV Loop Diuretics (LD) | CLINICAL: Total Number of Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge | 90 days after discharge | 66 Rehospitalizations |
Secondary
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.
Time frame: Within 30 days and 90 days after hospital discharge
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | CLINICAL: Total Number of Days for Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge | 30 days after discharge | 88 Days |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | CLINICAL: Total Number of Days for Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge | 90 days after discharge | 377 Days |
| IV Loop Diuretics (LD) | CLINICAL: Total Number of Days for Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge | 30 days after discharge | 207 Days |
| IV Loop Diuretics (LD) | CLINICAL: Total Number of Days for Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge | 90 days after discharge | 554 Days |
Secondary
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.
Time frame: Within 30 days and 90 days after hospital discharge
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | CLINICAL: Total Number of Days Rehospitalized for Heart Failure (HF) at 30 and 90 Days After Discharge | 30 days after discharge | 68 Days |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | CLINICAL: Total Number of Days Rehospitalized for Heart Failure (HF) at 30 and 90 Days After Discharge | 90 days after discharge | 338 Days |
| IV Loop Diuretics (LD) | CLINICAL: Total Number of Days Rehospitalized for Heart Failure (HF) at 30 and 90 Days After Discharge | 30 days after discharge | 172 Days |
| IV Loop Diuretics (LD) | CLINICAL: Total Number of Days Rehospitalized for Heart Failure (HF) at 30 and 90 Days After Discharge | 90 days after discharge | 460 Days |
Secondary
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
Time frame: Within 30 days and 90 days after hospital discharge
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | CLINICAL: Total Number of Emergency Department (ED) or Unscheduled Office Visits at 30 and 90 Days After Discharge | 30 days after discharge | 4 Visits |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | CLINICAL: Total Number of Emergency Department (ED) or Unscheduled Office Visits at 30 and 90 Days After Discharge | 90 days after discharge | 7 Visits |
| IV Loop Diuretics (LD) | CLINICAL: Total Number of Emergency Department (ED) or Unscheduled Office Visits at 30 and 90 Days After Discharge | 30 days after discharge | 5 Visits |
| IV Loop Diuretics (LD) | CLINICAL: Total Number of Emergency Department (ED) or Unscheduled Office Visits at 30 and 90 Days After Discharge | 90 days after discharge | 8 Visits |
Secondary
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.
Time frame: Within 30 days and 90 days after hospital discharge
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | CLINICAL: Total Number of Heart Failure (HF) Rehospitalizations at 30 and 90 Days After Discharge | 30 days after discharge | 11 Rehospitalizations |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | CLINICAL: Total Number of Heart Failure (HF) Rehospitalizations at 30 and 90 Days After Discharge | 90 days after discharge | 36 Rehospitalizations |
| IV Loop Diuretics (LD) | CLINICAL: Total Number of Heart Failure (HF) Rehospitalizations at 30 and 90 Days After Discharge | 30 days after discharge | 24 Rehospitalizations |
| IV Loop Diuretics (LD) | CLINICAL: Total Number of Heart Failure (HF) Rehospitalizations at 30 and 90 Days After Discharge | 90 days after discharge | 52 Rehospitalizations |
Secondary
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.
Time frame: Within 30 and 90 days after hospital discharge
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | Days Alive and Out of Hospital at 30 and 90 Days After Discharge | 30 days after discharge | 27.29 Days | Standard Deviation 5.78 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | Days Alive and Out of Hospital at 30 and 90 Days After Discharge | 90 days after discharge | 62 Days | Standard Deviation 24.57 |
| IV Loop Diuretics (LD) | Days Alive and Out of Hospital at 30 and 90 Days After Discharge | 30 days after discharge | 26.46 Days | Standard Deviation 6.34 |
| IV Loop Diuretics (LD) | Days Alive and Out of Hospital at 30 and 90 Days After Discharge | 90 days after discharge | 61.38 Days | Standard Deviation 24.95 |
Secondary
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
Population: Number of participants analyzed changes over time. Baseline: n=108 for AQ arm, n=109 for LD arm. 72 hours from baseline: n=81 for AQ arm, n=77 for LD arm. Discharge: n=83 for AQ arm, n=89 for LD arm. 90 days follow up: n=65 for AQ arm, n=76 for LD arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | EFFICACY: Changes in B-type Natriuretic Peptide (BNP) Levels Over Time | Baseline | 814.0 pg/mL | Standard Deviation 827.66 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | EFFICACY: Changes in B-type Natriuretic Peptide (BNP) Levels Over Time | 72 hours from baseline | -169.8 pg/mL | Standard Deviation 450.57 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | EFFICACY: Changes in B-type Natriuretic Peptide (BNP) Levels Over Time | Discharge | -250.2 pg/mL | Standard Deviation 527.12 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | EFFICACY: Changes in B-type Natriuretic Peptide (BNP) Levels Over Time | 90 days after discharge | -159.9 pg/mL | Standard Deviation 678.2 |
| IV Loop Diuretics (LD) | EFFICACY: Changes in B-type Natriuretic Peptide (BNP) Levels Over Time | 90 days after discharge | -201.3 pg/mL | Standard Deviation 618.31 |
| IV Loop Diuretics (LD) | EFFICACY: Changes in B-type Natriuretic Peptide (BNP) Levels Over Time | Baseline | 904.1 pg/mL | Standard Deviation 843.44 |
| IV Loop Diuretics (LD) | EFFICACY: Changes in B-type Natriuretic Peptide (BNP) Levels Over Time | Discharge | -219.1 pg/mL | Standard Deviation 539.26 |
| IV Loop Diuretics (LD) | EFFICACY: Changes in B-type Natriuretic Peptide (BNP) Levels Over Time | 72 hours from baseline | -120.5 pg/mL | Standard Deviation 469.04 |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | EFFICACY: Freedom From Congestion | 40 Participants |
| IV Loop Diuretics (LD) | EFFICACY: Freedom From Congestion | 46 Participants |
Secondary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | EFFICACY: Net Fluid Removed During the Index Hospitalization | 12921 mL | Standard Deviation 20564 |
| IV Loop Diuretics (LD) | EFFICACY: Net Fluid Removed During the Index Hospitalization | 8907 mL | Standard Deviation 13329 |
Secondary
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.
Time frame: Index Hospitalization, an average of 8 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | EFFICACY: Time to Freedom From Congestion | 5.28 Days | Standard Deviation 4.11 |
| IV Loop Diuretics (LD) | EFFICACY: Time to Freedom From Congestion | 3.86 Days | Standard Deviation 3.23 |
Secondary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | EFFICACY: Total Fluid Removed During the Index Hospitalization | 18700 mL | Standard Deviation 23033 |
| IV Loop Diuretics (LD) | EFFICACY: Total Fluid Removed During the Index Hospitalization | 14043 mL | Standard Deviation 15299 |
Secondary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | EFFICACY: Total Weight Loss During the Index Hospitalization | -17.12 lbs | Standard Deviation 12.59 |
| IV Loop Diuretics (LD) | EFFICACY: Total Weight Loss During the Index Hospitalization | -16.21 lbs | Standard Deviation 14.23 |
Secondary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | EFFICACY: Weight Loss at 72 Hours After Initiation of Treatment | -10.69 lbs | Standard Deviation 7.2 |
| IV Loop Diuretics (LD) | EFFICACY: Weight Loss at 72 Hours After Initiation of Treatment | -10.30 lbs | Standard Deviation 9.22 |
Secondary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | Length of Stay (LOS) During the Index Hospitalization | 8.49 Days | Standard Deviation 5.73 |
| IV Loop Diuretics (LD) | Length of Stay (LOS) During the Index Hospitalization | 7.19 Days | Standard Deviation 5.37 |
Secondary
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 frame: Time from randomization to 90 days post-hospital discharge
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | Mortality Rates Within Index Hospitalization or Within 90 Days After Hospital Discharge. | 15.45 Percentage of Participants |
| IV Loop Diuretics (LD) | Mortality Rates Within Index Hospitalization or Within 90 Days After Hospital Discharge. | 12.61 Percentage of Participants |
Secondary
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.
Time frame: Within 90 days after hospital discharge
Population: Number of participants analyzed changes over time. Baseline: n=107 for AQ arm, n=110 for LD arm. 30 day follow up: n=85 for AQ arm, n=91 for LD arm. 90 day follow up: n=72 for AQ arm, n=77 for LD arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | Quality of Life Assessed Using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 30, 60 and 90 Days After Discharge | Baseline | 25.39 Scores on a Scale | Standard Deviation 19.37 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | Quality of Life Assessed Using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 30, 60 and 90 Days After Discharge | 30 days after discharge | 52.06 Scores on a Scale | Standard Deviation 28.58 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | Quality of Life Assessed Using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 30, 60 and 90 Days After Discharge | 90 days after discharge | 59.72 Scores on a Scale | Standard Deviation 24.9 |
| IV Loop Diuretics (LD) | Quality of Life Assessed Using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 30, 60 and 90 Days After Discharge | Baseline | 28.64 Scores on a Scale | Standard Deviation 22.59 |
| IV Loop Diuretics (LD) | Quality of Life Assessed Using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 30, 60 and 90 Days After Discharge | 30 days after discharge | 49.36 Scores on a Scale | Standard Deviation 28.82 |
| IV Loop Diuretics (LD) | Quality of Life Assessed Using the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 30, 60 and 90 Days After Discharge | 90 days after discharge | 58.50 Scores on a Scale | Standard Deviation 26.72 |
Secondary
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
Time frame: Within 90 days of randomization
Population: Number of participants analyzed changes over time. Baseline: n=105 for AQ arm, n=108 for LD arm. 30 days after discharge: n=93 for AQ arm, n=95 for LD arm. 60 days after discharge: n=85 for AQ arm, n=84 for LD arm. 90 days after discharge: n=4 for AQ arm, n=6 for LD arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | SAFETY: Changes in Renal Function (Blood Urea Nitrogen) After Treatment up to 90 Days After Randomization | Discharge | 8.38 mg/dL | Standard Deviation 13.94 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | SAFETY: Changes in Renal Function (Blood Urea Nitrogen) After Treatment up to 90 Days After Randomization | 30 days after discharge | 1.72 mg/dL | Standard Deviation 14.44 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | SAFETY: Changes in Renal Function (Blood Urea Nitrogen) After Treatment up to 90 Days After Randomization | 60 days after discharge | 1.85 mg/dL | Standard Deviation 16.62 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | SAFETY: Changes in Renal Function (Blood Urea Nitrogen) After Treatment up to 90 Days After Randomization | 90 days after discharge | 2.50 mg/dL | Standard Deviation 6.36 |
| IV Loop Diuretics (LD) | SAFETY: Changes in Renal Function (Blood Urea Nitrogen) After Treatment up to 90 Days After Randomization | 90 days after discharge | -3.78 mg/dL | Standard Deviation 4.19 |
| IV Loop Diuretics (LD) | SAFETY: Changes in Renal Function (Blood Urea Nitrogen) After Treatment up to 90 Days After Randomization | Discharge | 7.62 mg/dL | Standard Deviation 14.34 |
| IV Loop Diuretics (LD) | SAFETY: Changes in Renal Function (Blood Urea Nitrogen) After Treatment up to 90 Days After Randomization | 60 days after discharge | 3.16 mg/dL | Standard Deviation 17.78 |
| IV Loop Diuretics (LD) | SAFETY: Changes in Renal Function (Blood Urea Nitrogen) After Treatment up to 90 Days After Randomization | 30 days after discharge | 6.56 mg/dL | Standard Deviation 22.8 |
Secondary
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
Time frame: Within 90 days of randomization
Population: Number of participants analyzed changes over time. Discharge: n=105 for AQ arm, n=108 for LD arm. 30 days after discharge: n=93 for AQ arm, n=95 for LD arm. 60 days after discharge: n=85 for AQ arm, n=84 for LD arm. 90 days after discharge: n=4 for AQ arm, n=6 for LD arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | SAFETY: Changes in Renal Function (Blood Urea Nitrogen/Serum Creatinine) After Treatment up to 90 Days After Randomization | Discharge | 3.77 mg/dL | Standard Deviation 7.8 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | SAFETY: Changes in Renal Function (Blood Urea Nitrogen/Serum Creatinine) After Treatment up to 90 Days After Randomization | 30 days after discharge | 0.28 mg/dL | Standard Deviation 6.88 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | SAFETY: Changes in Renal Function (Blood Urea Nitrogen/Serum Creatinine) After Treatment up to 90 Days After Randomization | 60 days after discharge | 0.07 mg/dL | Standard Deviation 7.07 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | SAFETY: Changes in Renal Function (Blood Urea Nitrogen/Serum Creatinine) After Treatment up to 90 Days After Randomization | 90 days after discharge | 5.66 mg/dL | Standard Deviation 1.4 |
| IV Loop Diuretics (LD) | SAFETY: Changes in Renal Function (Blood Urea Nitrogen/Serum Creatinine) After Treatment up to 90 Days After Randomization | 90 days after discharge | 1.72 mg/dL | Standard Deviation 5.56 |
| IV Loop Diuretics (LD) | SAFETY: Changes in Renal Function (Blood Urea Nitrogen/Serum Creatinine) After Treatment up to 90 Days After Randomization | Discharge | 3.03 mg/dL | Standard Deviation 6.52 |
| IV Loop Diuretics (LD) | SAFETY: Changes in Renal Function (Blood Urea Nitrogen/Serum Creatinine) After Treatment up to 90 Days After Randomization | 60 days after discharge | 1.97 mg/dL | Standard Deviation 7.42 |
| IV Loop Diuretics (LD) | SAFETY: Changes in Renal Function (Blood Urea Nitrogen/Serum Creatinine) After Treatment up to 90 Days After Randomization | 30 days after discharge | 1.65 mg/dL | Standard Deviation 8.85 |
Secondary
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
Time frame: Within 90 days of randomization
Population: Number of participants analyzed changes over time. Discharge: n=105 for AQ arm, n=108 for LD arm. 30 days after discharge: n=93 for AQ arm, n=95 for LD arm. 60 days after discharge: n=85 for AQ arm, n=84 for LD arm. 90 days after discharge: n=4 for AQ arm, n=6 for LD arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | SAFETY: Changes in Renal Function (Estimated Glomerular Filtration Rate) After Treatment up to 90 Days After Randomization | Discharge | -2.31 mL/min/1.73m2 | Standard Deviation 14.5 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | SAFETY: Changes in Renal Function (Estimated Glomerular Filtration Rate) After Treatment up to 90 Days After Randomization | 30 days after discharge | -0.56 mL/min/1.73m2 | Standard Deviation 14.24 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | SAFETY: Changes in Renal Function (Estimated Glomerular Filtration Rate) After Treatment up to 90 Days After Randomization | 60 days after discharge | -2.49 mL/min/1.73m2 | Standard Deviation 16.81 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | SAFETY: Changes in Renal Function (Estimated Glomerular Filtration Rate) After Treatment up to 90 Days After Randomization | 90 days after discharge | 5.70 mL/min/1.73m2 | Standard Deviation 8.06 |
| IV Loop Diuretics (LD) | SAFETY: Changes in Renal Function (Estimated Glomerular Filtration Rate) After Treatment up to 90 Days After Randomization | 90 days after discharge | 7.41 mL/min/1.73m2 | Standard Deviation 11.87 |
| IV Loop Diuretics (LD) | SAFETY: Changes in Renal Function (Estimated Glomerular Filtration Rate) After Treatment up to 90 Days After Randomization | Discharge | -2.68 mL/min/1.73m2 | Standard Deviation 13.45 |
| IV Loop Diuretics (LD) | SAFETY: Changes in Renal Function (Estimated Glomerular Filtration Rate) After Treatment up to 90 Days After Randomization | 60 days after discharge | 2.15 mL/min/1.73m2 | Standard Deviation 13.79 |
| IV Loop Diuretics (LD) | SAFETY: Changes in Renal Function (Estimated Glomerular Filtration Rate) After Treatment up to 90 Days After Randomization | 30 days after discharge | -3.33 mL/min/1.73m2 | Standard Deviation 14.97 |
Secondary
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
Time frame: Within 90 days of randomization
Population: Number of participants analyzed changes over time. Discharge: n=105 for AQ arm, n=108 for LD arm. 30 days after discharge: n=93 for AQ arm, n=95 for LD arm. 60 days after discharge: n=85 for AQ arm, n=84 for LD arm. 90 days after discharge: n=4 for AQ arm, n=6 for LD arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | SAFETY: Changes in Renal Function (Serum Creatinine) After Treatment up to 90 Days After Randomization | Discharge | 0.12 mg/dL | Standard Deviation 0.42 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | SAFETY: Changes in Renal Function (Serum Creatinine) After Treatment up to 90 Days After Randomization | 30 days after discharge | 0.37 mg/dL | Standard Deviation 3.41 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | SAFETY: Changes in Renal Function (Serum Creatinine) After Treatment up to 90 Days After Randomization | 60 days after discharge | 1.34 mg/dL | Standard Deviation 11.4 |
| Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration | SAFETY: Changes in Renal Function (Serum Creatinine) After Treatment up to 90 Days After Randomization | 90 days after discharge | -0.30 mg/dL | Standard Deviation 0.42 |
| IV Loop Diuretics (LD) | SAFETY: Changes in Renal Function (Serum Creatinine) After Treatment up to 90 Days After Randomization | 90 days after discharge | -0.24 mg/dL | Standard Deviation 0.3 |
| IV Loop Diuretics (LD) | SAFETY: Changes in Renal Function (Serum Creatinine) After Treatment up to 90 Days After Randomization | Discharge | 0.12 mg/dL | Standard Deviation 0.5 |
| IV Loop Diuretics (LD) | SAFETY: Changes in Renal Function (Serum Creatinine) After Treatment up to 90 Days After Randomization | 60 days after discharge | -0.01 mg/dL | Standard Deviation 0.44 |
| IV Loop Diuretics (LD) | SAFETY: Changes in Renal Function (Serum Creatinine) After Treatment up to 90 Days After Randomization | 30 days after discharge | 0.17 mg/dL | Standard Deviation 0.63 |