Trial Outcomes & Findings for Study of Heart Failure Hospitalizations After Aquapheresis Therapy Compared to Intravenous (IV) Diuretic Treatment (NCT NCT01474200)

NCT ID: NCT01474200

Last Updated: 2023-08-29

Results Overview

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

• Recruitment status: TERMINATED
• Study phase: NA
• Target enrollment: 224 participants
• Primary outcome timeframe: 90 days after discharge from index HF hospitalization.
• Results posted on: 2023-08-29

Participant Flow

Participant milestones

Measure	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.	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.
Overall Study STARTED	110	114
Overall Study COMPLETED	81	84
Overall Study NOT COMPLETED	29	30

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=110 Participants 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.	IV Loop Diuretics (LD) n=111 Participants 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.	Total n=221 Participants Total of all reporting groups
Age, Continuous	67.03 Years STANDARD_DEVIATION 12.61 • n=5 Participants	66.87 Years STANDARD_DEVIATION 13.45 • n=7 Participants	66.95 Years STANDARD_DEVIATION 13.01 • n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	30 Participants n=7 Participants	64 Participants n=5 Participants
Sex: Female, Male Male	76 Participants n=5 Participants	81 Participants n=7 Participants	157 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	31 Participants n=5 Participants	30 Participants n=7 Participants	61 Participants n=5 Participants
Race (NIH/OMB) White	75 Participants n=5 Participants	71 Participants n=7 Participants	146 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Height	172.45 Centimeters STANDARD_DEVIATION 11.04 • n=5 Participants	174.12 Centimeters STANDARD_DEVIATION 10.52 • n=7 Participants	173.29 Centimeters STANDARD_DEVIATION 10.79 • n=5 Participants
Weight	110.06 Kilograms STANDARD_DEVIATION 32.26 • n=5 Participants	110.92 Kilograms STANDARD_DEVIATION 35.09 • n=7 Participants	110.49 Kilograms STANDARD_DEVIATION 33.64 • n=5 Participants
Body Mass Index (BMI)	36.89 Kg/m2 STANDARD_DEVIATION 10.13 • n=5 Participants	36.32 Kg/m2 STANDARD_DEVIATION 10.10 • n=7 Participants	36.61 Kg/m2 STANDARD_DEVIATION 10.10 • n=5 Participants

PRIMARY outcome

Timeframe: 90 days after discharge from index HF hospitalization.

Population: Results reported are for the 25th percentile.

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

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=110 Participants 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.	IV Loop Diuretics (LD) n=111 Participants 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.
Time to First Heart Failure (HF) Event	62 Days Interval 42.0 to We are unable to estimate the upper limit of the confidence interval due to lack of events.	34 Days Interval 20.0 to 62.0

SECONDARY outcome

Timeframe: Index Hospitalization, an average of 8 days

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

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=108 Participants 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.	IV Loop Diuretics (LD) n=109 Participants 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.
EFFICACY: Total Fluid Removed During the Index Hospitalization	18700 mL Standard Deviation 23033	14043 mL Standard Deviation 15299

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=108 Participants 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.	IV Loop Diuretics (LD) n=109 Participants 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.
EFFICACY: Net Fluid Removed During the Index Hospitalization	12921 mL Standard Deviation 20564	8907 mL Standard Deviation 13329

SECONDARY outcome

Timeframe: 72 hours after treatment initiation

Weight at 72 hours after treatment initiation minus weight at treatment initiation. Negative mean values indicate weight loss.

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=85 Participants 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.	IV Loop Diuretics (LD) n=82 Participants 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.
EFFICACY: Weight Loss at 72 Hours After Initiation of Treatment	-10.69 lbs Standard Deviation 7.20	-10.30 lbs Standard Deviation 9.22

SECONDARY outcome

Timeframe: Index Hospitalization, an average of 8 days

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

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=104 Participants 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.	IV Loop Diuretics (LD) n=108 Participants 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.
EFFICACY: Total Weight Loss During the Index Hospitalization	-17.12 lbs Standard Deviation 12.59	-16.21 lbs Standard Deviation 14.23

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=40 Participants 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.	IV Loop Diuretics (LD) n=46 Participants 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.
EFFICACY: Time to Freedom From Congestion	5.28 Days Standard Deviation 4.11	3.86 Days Standard Deviation 3.23

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=110 Participants 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.	IV Loop Diuretics (LD) n=111 Participants 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.
EFFICACY: Freedom From Congestion	40 Participants	46 Participants

SECONDARY outcome

Timeframe: 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.

Change in BNP levels over time at 72 hours, discharge, and 90 days after discharge.

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=108 Participants 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.	IV Loop Diuretics (LD) n=109 Participants 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.
EFFICACY: Changes in B-type Natriuretic Peptide (BNP) Levels Over Time Baseline	814.0 pg/mL Standard Deviation 827.66	904.1 pg/mL Standard Deviation 843.44
EFFICACY: Changes in B-type Natriuretic Peptide (BNP) Levels Over Time 72 hours from baseline	-169.8 pg/mL Standard Deviation 450.57	-120.5 pg/mL Standard Deviation 469.04
EFFICACY: Changes in B-type Natriuretic Peptide (BNP) Levels Over Time Discharge	-250.2 pg/mL Standard Deviation 527.12	-219.1 pg/mL Standard Deviation 539.26
EFFICACY: Changes in B-type Natriuretic Peptide (BNP) Levels Over Time 90 days after discharge	-159.9 pg/mL Standard Deviation 678.20	-201.3 pg/mL Standard Deviation 618.31

SECONDARY outcome

Timeframe: Index hospitalization admission to index hospitalization discharge

Number of days patient is in hospital for HF treatment.

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=105 Participants 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.	IV Loop Diuretics (LD) n=108 Participants 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.
Length of Stay (LOS) During the Index Hospitalization	8.49 Days Standard Deviation 5.73	7.19 Days Standard Deviation 5.37

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=110 Participants 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.	IV Loop Diuretics (LD) n=111 Participants 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.
CLINICAL: Total Number of Days Rehospitalized for Heart Failure (HF) at 30 and 90 Days After Discharge 30 days after discharge	68 Days	172 Days
CLINICAL: Total Number of Days Rehospitalized for Heart Failure (HF) at 30 and 90 Days After Discharge 90 days after discharge	338 Days	460 Days

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=110 Participants 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.	IV Loop Diuretics (LD) n=111 Participants 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.
CLINICAL: Total Number of Emergency Department (ED) or Unscheduled Office Visits at 30 and 90 Days After Discharge 30 days after discharge	4 Visits	5 Visits
CLINICAL: Total Number of Emergency Department (ED) or Unscheduled Office Visits at 30 and 90 Days After Discharge 90 days after discharge	7 Visits	8 Visits

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=110 Participants 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.	IV Loop Diuretics (LD) n=111 Participants 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.
CLINICAL: Total Number of Heart Failure (HF) Rehospitalizations at 30 and 90 Days After Discharge 30 days after discharge	11 Rehospitalizations	24 Rehospitalizations
CLINICAL: Total Number of Heart Failure (HF) Rehospitalizations at 30 and 90 Days After Discharge 90 days after discharge	36 Rehospitalizations	52 Rehospitalizations

SECONDARY outcome

Timeframe: Within 30 days and 90 days after hospital discharge

CV symptoms that required hospitalization for treatment within 90 days of index hospitalization discharge.

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=110 Participants 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.	IV Loop Diuretics (LD) n=111 Participants 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.
CLINICAL: Total Number of Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge 30 days after discharge	17 Rehospitalizations	33 Rehospitalizations
CLINICAL: Total Number of Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge 90 days after discharge	46 Rehospitalizations	66 Rehospitalizations

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=110 Participants 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.	IV Loop Diuretics (LD) n=111 Participants 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.
CLINICAL: Total Number of Days for Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge 30 days after discharge	88 Days	207 Days
CLINICAL: Total Number of Days for Cardiovascular (CV) Rehospitalizations at 30 and 90 Days After Discharge 90 days after discharge	377 Days	554 Days

SECONDARY outcome

Timeframe: Within 30 days and 90 days after hospital discharge

Any cause that required hospitalization for treatment within 90 days of index hospitalization discharge.

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=110 Participants 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.	IV Loop Diuretics (LD) n=111 Participants 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.
CLINICAL: All Cause Rehospitalization Rates at 30 and 90 Days 30 days after discharge	0.899 Rehospitalizations/100 Pt-Days at Risk	1.278 Rehospitalizations/100 Pt-Days at Risk
CLINICAL: All Cause Rehospitalization Rates at 30 and 90 Days 90 days after discharge	1.109 Rehospitalizations/100 Pt-Days at Risk	1.237 Rehospitalizations/100 Pt-Days at Risk

SECONDARY outcome

Timeframe: Time from randomization to 90 days post-hospital discharge

Death due to any cause within index hospitalization and 90 days following hospital discharge.

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=110 Participants 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.	IV Loop Diuretics (LD) n=111 Participants 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.
Mortality Rates Within Index Hospitalization or Within 90 Days After Hospital Discharge.	15.45 Percentage of Participants	12.61 Percentage of Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=105 Participants 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.	IV Loop Diuretics (LD) n=108 Participants 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.
Days Alive and Out of Hospital at 30 and 90 Days After Discharge 30 days after discharge	27.29 Days Standard Deviation 5.78	26.46 Days Standard Deviation 6.34
Days Alive and Out of Hospital at 30 and 90 Days After Discharge 90 days after discharge	62 Days Standard Deviation 24.57	61.38 Days Standard Deviation 24.95

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=107 Participants 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.	IV Loop Diuretics (LD) n=110 Participants 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.
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	28.64 Scores on a Scale Standard Deviation 22.59
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	49.36 Scores on a Scale Standard Deviation 28.82
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 24.90	58.50 Scores on a Scale Standard Deviation 26.72

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=107 Participants 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.	IV Loop Diuretics (LD) n=110 Participants 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.
CLINICAL: Global Clinical Score at 30 and 90 Days After Discharge Baseline	28.26 Scores on a Scale Standard Deviation 18.65	31.83 Scores on a Scale Standard Deviation 18.63
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	53.08 Scores on a Scale Standard Deviation 26.01
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	60.56 Scores on a Scale Standard Deviation 26.34

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=105 Participants 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.	IV Loop Diuretics (LD) n=108 Participants 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.
SAFETY: Changes in Renal Function (Serum Creatinine) After Treatment up to 90 Days After Randomization Discharge	0.12 mg/dL Standard Deviation 0.42	0.12 mg/dL Standard Deviation 0.50
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	0.17 mg/dL Standard Deviation 0.63
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 11.40	-0.01 mg/dL Standard Deviation 0.44
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	-0.24 mg/dL Standard Deviation 0.30

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=105 Participants 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.	IV Loop Diuretics (LD) n=108 Participants 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.
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	7.62 mg/dL Standard Deviation 14.34
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	6.56 mg/dL Standard Deviation 22.80
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	3.16 mg/dL Standard Deviation 17.78
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	-3.78 mg/dL Standard Deviation 4.19

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=105 Participants 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.	IV Loop Diuretics (LD) n=108 Participants 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.
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 7.80	3.03 mg/dL Standard Deviation 6.52
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	1.65 mg/dL Standard Deviation 8.85
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	1.97 mg/dL Standard Deviation 7.42
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 1.40	1.72 mg/dL Standard Deviation 5.56

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=105 Participants 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.	IV Loop Diuretics (LD) n=108 Participants 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.
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 14.50	-2.68 mL/min/1.73m2 Standard Deviation 13.45
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	-3.33 mL/min/1.73m2 Standard Deviation 14.97
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	2.15 mL/min/1.73m2 Standard Deviation 13.79
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	7.41 mL/min/1.73m2 Standard Deviation 11.87

Adverse Events

Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration

Serious events: 73 serious events

Other events: 25 other events

Deaths: 0 deaths

IV Loop Diuretics (LD)

Serious events: 67 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=110 participants at risk 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.	IV Loop Diuretics (LD) n=111 participants at risk 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.
Cardiac disorders Cardiac Failure	4.5% 5/110 • Baseline through 90 days after discharge.	7.2% 8/111 • Baseline through 90 days after discharge.
Cardiac disorders Cardiac Failure Acute	11.8% 13/110 • Baseline through 90 days after discharge.	17.1% 19/111 • Baseline through 90 days after discharge.
Cardiac disorders Cardiac Failure Congestive	10.0% 11/110 • Baseline through 90 days after discharge.	18.0% 20/111 • Baseline through 90 days after discharge.
General disorders Chest Pain	3.6% 4/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Infections and infestations Pneumonia	4.5% 5/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Investigations Blood Creatinine Increase	3.6% 4/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Renal and urinary disorders Renal Failure Acute	3.6% 4/110 • Baseline through 90 days after discharge.	2.7% 3/111 • Baseline through 90 days after discharge.
Vascular disorders Hypotension	2.7% 3/110 • Baseline through 90 days after discharge.	4.5% 5/111 • Baseline through 90 days after discharge.
Cardiac disorders Acute Coronary Syndrom	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Cardiac disorders Acute Myocardial Infarction	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Cardiac disorders Arrhythmia	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Cardiac disorders Atrial Fibrillation	2.7% 3/110 • Baseline through 90 days after discharge.	1.8% 2/111 • Baseline through 90 days after discharge.
Cardiac disorders Atrioventricular Block Second Degree	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Cardiac disorders Cardiac Arrest	2.7% 3/110 • Baseline through 90 days after discharge.	1.8% 2/111 • Baseline through 90 days after discharge.
Cardiac disorders Cardiac Failure Chronic	1.8% 2/110 • Baseline through 90 days after discharge.	2.7% 3/111 • Baseline through 90 days after discharge.
Cardiac disorders Cardio-Respiratory Arrest	1.8% 2/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Cardiac disorders Cardiogenic Shock	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Cardiac disorders Cardiomyopathy	0.91% 1/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Cardiac disorders Cardiorenal Syndrome	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Cardiac disorders Cardiovascular Insufficiency	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Cardiac disorders Congestive Cardiomyopathy	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Cardiac disorders Cor Pulmonale	0.00% 0/110 • Baseline through 90 days after discharge.	1.8% 2/111 • Baseline through 90 days after discharge.
Cardiac disorders Ischaemic Cardiomyopathy	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Cardiac disorders Myocardial Infarction	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Cardiac disorders Palpitations	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Cardiac disorders Right Ventricular Failure	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Cardiac disorders Supra Ventricular Tachycardia	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Cardiac disorders Ventricular Tachycardia	1.8% 2/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Gastrointestinal disorders Abdominal Pain Lower	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Gastrointestinal disorders Abdominal Pain Upper	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Gastrointestinal disorders Abdominal Wall Haematoma	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Gastrointestinal disorders Gastric Antral Vascular Ectasia	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Gastrointestinal disorders Gastrointestinal Haemorrhage	1.8% 2/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Gastrointestinal disorders Lower Gastrointestinal Haemorrhage	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Gastrointestinal disorders Pancreatitis	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Gastrointestinal disorders Upper Gastrointestinal Haemorrhage	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
General disorders Cardiac Death	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
General disorders Chest Discomfort	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
General disorders Death	0.00% 0/110 • Baseline through 90 days after discharge.	2.7% 3/111 • Baseline through 90 days after discharge.
General disorders Device Lead Issue	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
General disorders Malaise	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
General disorders Medical Device Complication	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
General disorders Non-Cardiac Chest Pain	0.91% 1/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
General disorders Pain	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
General disorders Pyrexia	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Hepatobiliary disorders Gallbladder Perforation	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Immune system disorders Sarcoidosis	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Infections and infestations Cellulitis	1.8% 2/110 • Baseline through 90 days after discharge.	1.8% 2/111 • Baseline through 90 days after discharge.
Infections and infestations Filariasis	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Infections and infestations Infection	1.8% 2/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Infections and infestations Sepsis	0.91% 1/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Infections and infestations Septic Shock	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Infections and infestations Staphylococcal Infection	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Infections and infestations Upper Respiratory Tract Infection	1.8% 2/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Infections and infestations Urinary Tract Infection	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Infections and infestations Wound Infection	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Injury, poisoning and procedural complications Hip Fracture	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Injury, poisoning and procedural complications Procedural Haemorrhage	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Injury, poisoning and procedural complications Renal Haematoma	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Injury, poisoning and procedural complications Spinal Compression Fracture	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Injury, poisoning and procedural complications Vascular Graft Thrombosis	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Investigations Anticoagulation Drug Level Below Therapeautic	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Investigations Cardiac Output Decreased	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Investigations Haematocrit Decreased	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Investigations International Normalised Ratio Increased	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Metabolism and nutrition disorders Dehydration	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Metabolism and nutrition disorders Fluid Overload	0.91% 1/110 • Baseline through 90 days after discharge.	2.7% 3/111 • Baseline through 90 days after discharge.
Metabolism and nutrition disorders Hyperkalaemia	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Metabolism and nutrition disorders Hypoglycaemia	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Musculoskeletal and connective tissue disorders Cervical Spinal Stenosis	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Nervous system disorders Cerebrovascular Accident	0.91% 1/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Nervous system disorders Cerebrovascular Disorder	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Nervous system disorders Encephalopathy	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Nervous system disorders Headache	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Nervous system disorders Neurological Symptom	1.8% 2/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Nervous system disorders Neuropathy Peripheral	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Nervous system disorders Presyncope	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Nervous system disorders Syncope	1.8% 2/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Nervous system disorders Transient Ischaemic Attack	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Psychiatric disorders Confusional State	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Psychiatric disorders Depression	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Renal and urinary disorders Haematuria	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Renal and urinary disorders Renal Failure	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Renal and urinary disorders Renal Failure Chronic	1.8% 2/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Renal and urinary disorders Renal Impairment	0.91% 1/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	0.91% 1/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Respiratory, thoracic and mediastinal disorders Chronic Respiratory Failure	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.7% 3/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Respiratory, thoracic and mediastinal disorders Pickwickian Syndrome	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.91% 1/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Respiratory, thoracic and mediastinal disorders Pulmonary Hypertension	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Respiratory, thoracic and mediastinal disorders Respiratory Distress	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Surgical and medical procedures Cardiac Ablation	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Surgical and medical procedures Cardioversion	0.91% 1/110 • Baseline through 90 days after discharge.	1.8% 2/111 • Baseline through 90 days after discharge.
Surgical and medical procedures Implantable Defibrillator Insertion	2.7% 3/110 • Baseline through 90 days after discharge.	0.00% 0/111 • Baseline through 90 days after discharge.
Surgical and medical procedures Ventricular Assist Device Insertion	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Vascular disorders Deep Vein Thrombosis	0.91% 1/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Vascular disorders Hypertensive Crisis	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.
Vascular disorders Orthostatic Hypotension	0.00% 0/110 • Baseline through 90 days after discharge.	0.90% 1/111 • Baseline through 90 days after discharge.

Other adverse events

Measure	Aquapheresis (AQ) - Isolated Veno-venous Ultrafiltration n=110 participants at risk 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.	IV Loop Diuretics (LD) n=111 participants at risk 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.
Investigations Blood Creatinine Increase	6.4% 7/110 • Baseline through 90 days after discharge.	3.6% 4/111 • Baseline through 90 days after discharge.
Vascular disorders Hypotension	10.9% 12/110 • Baseline through 90 days after discharge.	6.3% 7/111 • Baseline through 90 days after discharge.
Infections and infestations Urinary Tract Infection	2.7% 3/110 • Baseline through 90 days after discharge.	6.3% 7/111 • Baseline through 90 days after discharge.
Metabolism and nutrition disorders Hyperkalaemia	7.3% 8/110 • Baseline through 90 days after discharge.	3.6% 4/111 • Baseline through 90 days after discharge.
Renal and urinary disorders Renal Failure Acute	4.5% 5/110 • Baseline through 90 days after discharge.	6.3% 7/111 • Baseline through 90 days after discharge.

Additional Information

Drew Jones, MD, Senior Medical Director

Baxter Healthcare Corporation

Phone: 224-270-2659

Email: drew_jones@baxter.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER