Study of Heart Failure Hospitalizations After Aquapheresi... | NCT01474200

Label	Type	Description	Intervention Names
Aquapheresis (AQ) - isolated veno-venous ultrafiltration	Experimental	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)
IV Loop Diuretics (LD)	Active Comparator	Excess fluid from the patient is removed by IV (Intravenous) loop diuretic treatment	Drug: IV Loop Diuretics (LD)

Name	Type	Description	Arm Group Labels	Other Names
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)

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.

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

Eligibility Module

Eligibility Criteria

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:
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.
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

Name	Affiliation	Role
Maria Rosa Costanzo, MD	Midwest Heart Foundation	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Heart Center Research		Huntsville	Alabama	35801	United States
Mayo Clinic - Scottsdale

PubMed Identifier	Type	Citation	Retractions
17291932	Background	Costanzo MR, Guglin ME, Saltzberg MT, Jessup ML, Bart BA, Teerlink JR, Jaski BE, Fang JC, Feller ED, Haas GJ, Anderson AS, Schollmeyer MP, Sobotka PA; UNLOAD Trial Investigators. Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure. J Am Coll Cardiol. 2007 Feb 13;49(6):675-83. doi: 10.1016/j.jacc.2006.07.073. Epub 2007 Jan 26.
15846257

ID	Title	Description
FG000	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.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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

Results reported are for the 25th percentile.

Posted

Median

95% Confidence Interval

Days

90 days after discharge from index HF hospitalization.

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG000110 OG001111

Title

Denominators

Categories

Title	Measurements
	OG00062(42 to NA)We are unable to estimate the upper limit of the confidence interval due to lack of events. OG00134(20 to 62)

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

Posted

Mean

Standard Deviation

Index Hospitalization, an average of 8 days

ID	Title	Description
OG000	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.
OG001	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.

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.

Posted

Mean

Standard Deviation

Index Hospitalization, an average of 8 days

ID	Title	Description
OG000	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.
OG001	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.

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.

Posted

Mean

Standard Deviation

lbs

72 hours after treatment initiation

ID	Title	Description
OG000	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.
OG001	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.

Secondary

EFFICACY: Total Weight Loss During the Index Hospitalization

Weight at hospital discharge minus weight at hospital admission. Negative mean values indicate weight loss.

Posted

Mean

Standard Deviation

lbs

Index Hospitalization, an average of 8 days

ID	Title	Description
OG000	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.
OG001	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.

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.

Posted

Mean

Standard Deviation

Days

Index Hospitalization, an average of 8 days

ID	Title	Description
OG000	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.
OG001	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.

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

Posted

Number

Participants

Index Hospitalization, an average of 8 days

ID	Title	Description
OG000	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.
OG001	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.

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.

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.

Posted

Mean

Standard Deviation

pg/mL

Baseline and at 72 hours from baseline, hospital discharge and at 90 days after hospital discharge

ID	Title	Description
OG000	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.
OG001	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.

Secondary

Length of Stay (LOS) During the Index Hospitalization

Number of days patient is in hospital for HF treatment.

Posted

Mean

Standard Deviation

Days

Index hospitalization admission to index hospitalization discharge

ID	Title	Description
OG000	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.
OG001	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.

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.

Posted

Number

Days

Within 30 days and 90 days after hospital discharge

ID	Title	Description
OG000	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.
OG001	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.

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

Posted

Number

Visits

Within 30 days and 90 days after hospital discharge

ID	Title	Description
OG000	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.
OG001	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.

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.

Posted

Number

Rehospitalizations

Within 30 days and 90 days after hospital discharge

ID	Title	Description
OG000	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.
OG001	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.

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.

Posted

Number

Rehospitalizations

Within 30 days and 90 days after hospital discharge

ID	Title	Description
OG000	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.
OG001	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.

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.

Posted

Number

Days

Within 30 days and 90 days after hospital discharge

ID	Title	Description
OG000	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.
OG001	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.

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.

Posted

Number

Rehospitalizations/100 Pt-Days at Risk

Within 30 days and 90 days after hospital discharge

ID	Title	Description
OG000	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.
OG001	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.

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.

Posted

Number

Percentage of Participants

Time from randomization to 90 days post-hospital discharge

ID	Title	Description
OG000	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.
OG001	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.

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.

Posted

Mean

Standard Deviation

Days

Within 30 and 90 days after hospital discharge

ID	Title	Description
OG000	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.
OG001	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.

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.

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.

Posted

Mean

Standard Deviation

Scores on a Scale

Within 90 days after hospital discharge

ID	Title	Description
OG000	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.
OG001	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.

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.

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.

Posted

Mean

Standard Deviation

Scores on a Scale

Within 90 days after hospital discharge

ID	Title	Description
OG000	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.
OG001	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.

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

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.

Posted

Mean

Standard Deviation

mg/dL

Within 90 days of randomization

ID	Title	Description
OG000	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.
OG001	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.

Secondary

SAFETY: Changes in Renal Function (Blood Urea Nitrogen) After Treatment up to 90 Days After Randomization

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.

Posted

Mean

Standard Deviation

mg/dL

Within 90 days of randomization

ID	Title	Description
OG000	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.
OG001	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.

Secondary

SAFETY: Changes in Renal Function (Blood Urea Nitrogen/Serum Creatinine) After Treatment up to 90 Days After Randomization

Posted

Mean

Standard Deviation

mg/dL

Within 90 days of randomization

ID	Title	Description
OG000	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.
OG001	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.

Secondary

SAFETY: Changes in Renal Function (Estimated Glomerular Filtration Rate) After Treatment up to 90 Days After Randomization

Posted

Mean

Standard Deviation

mL/min/1.73m2

Within 90 days of randomization

ID	Title	Description
OG000	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.
OG001	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.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cardiac Failure	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0005 affected110 at risk EG0018 affected111 at risk
Cardiac Failure Acute	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG00013 affected110 at risk EG00119 affected111 at risk
Cardiac Failure Congestive	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG00011 affected110 at risk EG00120 affected111 at risk
Chest Pain	General disorders	MedDRA (16.1)	Systematic Assessment	EG0004 affected110 at risk EG0011 affected111 at risk
Pneumonia	Infections and infestations	MedDRA (16.1)	Systematic Assessment	EG0005 affected110 at risk EG0010 affected111 at risk
Blood Creatinine Increase	Investigations	MedDRA (16.1)	Systematic Assessment	EG0004 affected110 at risk EG0010 affected111 at risk
Renal Failure Acute	Renal and urinary disorders	MedDRA (16.1)	Systematic Assessment	EG0004 affected110 at risk EG0013 affected111 at risk
Hypotension	Vascular disorders	MedDRA (16.1)	Systematic Assessment	EG0003 affected110 at risk EG0015 affected111 at risk
Acute Coronary Syndrom	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Acute Myocardial Infarction	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Arrhythmia	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Atrial Fibrillation	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0003 affected110 at risk EG0012 affected111 at risk
Atrioventricular Block Second Degree	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Cardiac Arrest	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0003 affected110 at risk EG0012 affected111 at risk
Cardiac Failure Chronic	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0002 affected110 at risk EG0013 affected111 at risk
Cardio-Respiratory Arrest	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0002 affected110 at risk EG0011 affected111 at risk
Cardiogenic Shock	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Cardiomyopathy	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0011 affected111 at risk
Cardiorenal Syndrome	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Cardiovascular Insufficiency	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Congestive Cardiomyopathy	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Cor Pulmonale	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0012 affected111 at risk
Ischaemic Cardiomyopathy	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Myocardial Infarction	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Palpitations	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Right Ventricular Failure	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Supra Ventricular Tachycardia	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Ventricular Tachycardia	Cardiac disorders	MedDRA (16.1)	Systematic Assessment	EG0002 affected110 at risk EG0010 affected111 at risk
Abdominal Pain Lower	Gastrointestinal disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Abdominal Pain Upper	Gastrointestinal disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Abdominal Wall Haematoma	Gastrointestinal disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Gastric Antral Vascular Ectasia	Gastrointestinal disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA (16.1)	Systematic Assessment	EG0002 affected110 at risk EG0011 affected111 at risk
Lower Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Upper Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Cardiac Death	General disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Chest Discomfort	General disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Death	General disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0013 affected111 at risk
Device Lead Issue	General disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Malaise	General disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Medical Device Complication	General disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Non-Cardiac Chest Pain	General disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0011 affected111 at risk
Pain	General disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Pyrexia	General disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Gallbladder Perforation	Hepatobiliary disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Sarcoidosis	Immune system disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Cellulitis	Infections and infestations	MedDRA (16.1)	Systematic Assessment	EG0002 affected110 at risk EG0012 affected111 at risk
Filariasis	Infections and infestations	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Infection	Infections and infestations	MedDRA (16.1)	Systematic Assessment	EG0002 affected110 at risk EG0010 affected111 at risk
Sepsis	Infections and infestations	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0011 affected111 at risk
Septic Shock	Infections and infestations	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Staphylococcal Infection	Infections and infestations	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDRA (16.1)	Systematic Assessment	EG0002 affected110 at risk EG0010 affected111 at risk
Urinary Tract Infection	Infections and infestations	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Wound Infection	Infections and infestations	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Hip Fracture	Injury, poisoning and procedural complications	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Procedural Haemorrhage	Injury, poisoning and procedural complications	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Renal Haematoma	Injury, poisoning and procedural complications	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Spinal Compression Fracture	Injury, poisoning and procedural complications	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Vascular Graft Thrombosis	Injury, poisoning and procedural complications	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Anticoagulation Drug Level Below Therapeautic	Investigations	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Cardiac Output Decreased	Investigations	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Haematocrit Decreased	Investigations	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
International Normalised Ratio Increased	Investigations	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Fluid Overload	Metabolism and nutrition disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0013 affected111 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Cervical Spinal Stenosis	Musculoskeletal and connective tissue disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Cerebrovascular Accident	Nervous system disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0011 affected111 at risk
Cerebrovascular Disorder	Nervous system disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Encephalopathy	Nervous system disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Headache	Nervous system disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Neurological Symptom	Nervous system disorders	MedDRA (16.1)	Systematic Assessment	EG0002 affected110 at risk EG0011 affected111 at risk
Neuropathy Peripheral	Nervous system disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Presyncope	Nervous system disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Syncope	Nervous system disorders	MedDRA (16.1)	Systematic Assessment	EG0002 affected110 at risk EG0011 affected111 at risk
Transient Ischaemic Attack	Nervous system disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Confusional State	Psychiatric disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Depression	Psychiatric disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Haematuria	Renal and urinary disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Renal Failure	Renal and urinary disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Renal Failure Chronic	Renal and urinary disorders	MedDRA (16.1)	Systematic Assessment	EG0002 affected110 at risk EG0010 affected111 at risk
Renal Impairment	Renal and urinary disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0010 affected111 at risk
Acute Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0011 affected111 at risk
Chronic Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (16.1)	Systematic Assessment	EG0003 affected110 at risk EG0010 affected111 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Pickwickian Syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0011 affected111 at risk
Pulmonary Hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Respiratory Distress	Respiratory, thoracic and mediastinal disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Cardiac Ablation	Surgical and medical procedures	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Cardioversion	Surgical and medical procedures	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0012 affected111 at risk
Implantable Defibrillator Insertion	Surgical and medical procedures	MedDRA (16.1)	Systematic Assessment	EG0003 affected110 at risk EG0010 affected111 at risk
Ventricular Assist Device Insertion	Surgical and medical procedures	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Deep Vein Thrombosis	Vascular disorders	MedDRA (16.1)	Systematic Assessment	EG0001 affected110 at risk EG0011 affected111 at risk
Hypertensive Crisis	Vascular disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk
Orthostatic Hypotension	Vascular disorders	MedDRA (16.1)	Systematic Assessment	EG0000 affected110 at risk EG0011 affected111 at risk

ID	Term
D006331	Heart Diseases
D002318	Cardiovascular Diseases

ID	Term
D014462	Ultrafiltration
D049994	Sodium Potassium Chloride Symporter Inhibitors
D005665	Furosemide

ID	Term
D005112	Extracorporeal Circulation
D013514	Surgical Procedures, Operative
D005374	Filtration
D002623	Chemistry Techniques, Analytical
D008919	Investigative Techniques
D055585	Physical Phenomena
D055598	Chemical Phenomena
D049990	Membrane Transport Modulators
D045504	Molecular Mechanisms of Pharmacological Action
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses
D004232	Diuretics
D045283	Natriuretic Agents
D045505	Physiological Effects of Drugs
D013424	Sulfanilamides
D013449	Sulfonamides
D000577	Amides
D009930	Organic Chemicals
D000814	Aniline Compounds
D000588	Amines
D013450	Sulfones
D013457	Sulfur Compounds

ID	Title	Description
BG000	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.
BG001	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.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.			73	110	25	110
EG001	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.			67	111	18	111