Clinical trial NCT04572867: Aquapheresis Efficacy in Outpatients With Decompensated Heart Failure
Official title: Efficacy of Aquapheresis in Patients Treated as Outpatients With Decompensated Heart Failure at a Veterans Hospital
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Heart Failure
Congestive Heart Failure
Decompensated Heart Failure
Keywords: Aquapheresis
Diuresis
Lead sponsor: James A. Haley Veterans Administration Hospital
Sponsor class: FED
First posted: 2020-10-01
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a Controlled Trial with two arms (aquapheresis and IV diuretics/Control), but there is the potential for cross-over to aquapheresis if a patient receiving diuretics is refractory to maximum doses of IV diuretics.
Primary purpose: TREATMENT

Brief summary: With this research the Investigators hope to learn if early aquapheresis in an outpatient setting will improve congestive heart failure symptoms in outpatients with decompensated heart failure who have been refractory to high dose diuretics. In previous trials in inpatient settings, aquapheresis has been demonstrated to improve quality of life and reduce hospital visits for those who have undergone the treatment. This study is one of the first to evaluate the effectiveness of aquapheresis in veterans with congestive heart failure in an outpatient setting.

The aquapheresis device, Aquadex FlexFlow® System, manufactured by CHF Solutions™, Minneapolis, MN, has been approved by the Food and Drug Administration (FDA) for removing excess sodium and fluid from patients suffering from volume overload, like in congestive heart failure.

Detailed description: Congestive heart failure (CHF) affects nearly 2% of the U.S. population, with almost 1 million hospital admissions for acute decompensated CHF annually. Congestive heart failure is the most frequent cause of hospitalization in patients over the age of 65. Patients admitted for acute decompensated heart failure (ADHF) have a high 6-month readmission rate for acute CHF, ranging from 23% to 40% in different studies. It is estimated that 25 to 30% of these patients are diuretic resistant with 50% of patients losing less than 5 lbs. from admission weight and 20% actually gaining weight during the hospitalization.

Although loop diuretics have not been shown to improve survival in patients with CHF, they effectively alleviate symptoms of congestion. Diuretics have been part of standard CHF therapy in all recent survival trials of β-blockers, angiotensin converting enzyme inhibitors, and angiotensin II receptor blockers. Loop diuretics have been shown to be the most effective diuretics as single agents in moderate to severe heart failure. However, loop diuretics may be associated with increased morbidity and mortality attributable to deleterious effects on neurohormonal activation, electrolyte balance, and cardiac and renal function.

Removal of excessive fluid in patients with CHF is usually achieved by a combination of fluid and salt restriction and loop diuretics, but in some cases volume overload persists. Diuretic resistance is common, especially after chronic exposure to loop diuretics; patients require escalating doses (PO or IV to bypass delayed absorption in gut due to bowel edema), addition of another diuretic that works on different part of renal tubules (i.e. Thiazides) +/- diuretic drip and, if still refractory, ultimately Aquapheresis (a form of ultrafiltration).

Aquapheresis (AQ) compared to IV diuretics in the UNLOAD Trial (10), AQ safely produced greater weight loss, fluid removal, and reduction in 90-day readmission rate compared to IV diuretic. A meta-analysis of 10 randomized control trials (RCTs) showed AQ not only to be effective but safe. These observations suggest that a strategy of early ultrafiltration may improve responsiveness to diuretics, quicker weight loss, decrease hospitalization, readmission to hospital, ER or doctor visits with minimal risks. As result of these trials, American Hospital Association (AHA)/American College of Cardiology (ACC)/Heart Failure Society of American (HFSA) guidelines state it is reasonable to start Aquapheresis in patients with obvious volume overload or patients who are refractory to high dose diuretics (IIa, LOE B). Moreover, while this therapy is part of standard of care in an inpatient setting, many hospitals as a result of Affordable Care Act (ACA), have taken to AQ on an outpatient setting to further decrease the burden and attended cost associated with management of CHF. But the Investigators are unaware of any other prospective outpatient studies that have looked at the outcomes and cost effectiveness of aquapheresis.

Eligibility criteria: Inclusion Criteria:

Subjects must be 18 years of age or older already on standard of care therapy including Angiotensin Converting Enzyme Inhibitors (ACE-I), Angiotensin

Receptor Blockers (ARBs), Sacubitril/Valsartan, beta-blocker, oral diuretic (80 mg Lasix/2 mg Bumex/40 mg Torsemide+/-Thiazide diuretic), and meet the following inclusion criteria to be enrolled:

Inclusion Criteria:

1. CHF refractory to oral diuretic (80mg Lasix, 2mg Bumex, or 40mg Torsemide)
2. Volume overload secondary to systolic or diastolic HF, evidenced by at least 2 of the following:

   1. Elevated BNP (\>100)
   2. Paroxysmal nocturnal dyspnea or orthopnea
   3. Elevated jugular venous distention (\>/ 7 cm)
   4. X-ray findings consisted with CHF
   5. Presence of ascites or LE edema . -

Exclusion Criteria:

1. Acute Coronary Syndrome
2. Hypertensive urgency or emergency
3. Rapid atrial fibrillation difficult to control
4. Contraindication to anticoagulation
5. Pregnancy
6. Requires hemodialysis (\> CR \> 3.0 mg/dl)
7. Symptomatic hypotension
8. Poor venous access
9. Pressor dependent. -

Primary outcomes:
measure: Number of Hospitalizations by 7 days post-treatment
timeFrame: Between outpatient treatment and 7-days after outpatient treatment
measure: Number of Hospitalizations by 30 days post-treatment
timeFrame: Between outpatient treatment and 30 days after outpatient treatment
measure: Number of Hospitalizations by 60 days post-treatment
timeFrame: Between outpatient treatment and 60 days after outpatient treatment
measure: Number of Hospitalizations by 90 days post-treatment
timeFrame: Between outpatient treatment and 90 days after outpatient treatment
measure: Weight change by 7 days post-treatment
timeFrame: Outpatient treatment to 7 days after outpatient treatment
measure: Weight change by 30 days post-treatment
timeFrame: Outpatient treatment to 30 days after outpatient treatment
measure: Weight change by 60 days post-treatment
timeFrame: Outpatient treatment to 60 days after outpatient treatment
measure: Weight change by 90 days post-treatment
timeFrame: Outpatient treatment to 90 days after outpatient treatment
Secondary outcomes:
measure: Total fluid removal
timeFrame: Baseline (Randomization) to outpatient discharge
measure: Blood urea nitrogen at Baseline
timeFrame: Baseline (Randomization)
measure: Blood urea nitrogen at 7 days post-treatment
timeFrame: 7 days after outpatient treatment
measure: Blood urea nitrogen at 30 days post-treatment
timeFrame: 30 days after outpatient treatment
measure: Blood urea nitrogen at 60 days post-treatment
timeFrame: 60 days after outpatient treatment
measure: Blood urea nitrogen at 90 days post-treatment
timeFrame: 90 days after outpatient treatment
measure: Creatinine at Baseline
timeFrame: Baseline (Randomization)
measure: Creatinine at 7 days post-treatment
timeFrame: 7 days after outpatient treatment
measure: Creatinine at 30 days post-treatment
timeFrame: 30 days after outpatient treatment
measure: Creatinine at 60 days post-treatment
timeFrame: 60 days after outpatient treatment
measure: Creatinine at 90 days post-treatment
timeFrame: 90 days after outpatient treatment
measure: Glomerular filtration rate at Baseline
timeFrame: Baseline (Randomization)
measure: Glomerular filtration rate at 7 days post-treatment
timeFrame: 7 days after outpatient treatment
measure: Glomerular filtration rate at 30 days post-treatment
timeFrame: 30 days after outpatient treatment
measure: Glomerular filtration rate at 60 days post-treatment
timeFrame: 60 days after outpatient treatment
measure: Glomerular filtration rate at 90 days post-treatment
timeFrame: 90 days after outpatient treatment
measure: Brain natriuretic peptide (BNP) test at Baseline
timeFrame: Baseline (Randomization)
measure: Brain natriuretic peptide (BNP) test at 7 days post-treatment
timeFrame: 7 days after outpatient treatment
measure: Brain natriuretic peptide (BNP) test at 30 days post-treatment
timeFrame: 30 days after outpatient treatment
measure: Brain natriuretic peptide (BNP) test at 60 days post-treatment
timeFrame: 60 days after outpatient treatment
measure: Brain natriuretic peptide (BNP) test at 90 days post-treatment
timeFrame: 90 days after outpatient treatment
measure: 6-minute Walk Test at Baseline
timeFrame: Baseline (Randomization)
measure: 6-minute Walk Test at 7 days post-treatment
timeFrame: 7 days after outpatient treatment
measure: 6-minute Walk Test at 30 days post-treatment
timeFrame: 30 days after outpatient treatment
measure: 6-minute Walk Test at 60 days post-treatment
timeFrame: 60 days after outpatient treatment
measure: 6-minute Walk Test at 90 days post-treatment
timeFrame: 90 days after outpatient treatment
measure: Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
timeFrame: Baseline (Randomization)
measure: Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
timeFrame: 7 days after outpatient treatment
measure: Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
timeFrame: 30 days after outpatient treatment
measure: Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
timeFrame: 60 days after outpatient treatment
measure: Minnesota Living with Heart Failure Questionnaire (MLWHFQ)
timeFrame: 90 days after outpatient treatment
measure: SF-36 at Baseline
timeFrame: Baseline (Randomization)
measure: SF-36 at 7 days post-treatment
timeFrame: 7 days after outpatient treatment
measure: SF-36 at 30 days post-treatment
timeFrame: 30 days after outpatient treatment
measure: SF-36 at 60 days post-treatment
timeFrame: 60 days after outpatient treatment
measure: SF-36 at 90 days post-treatment
timeFrame: 90 days after outpatient treatment
measure: Adverse events: bleeding incidents during Outpatient treatment
timeFrame: Start of treatment to discharge, which is usually the same day, but up to 3 days post-treatment, if medically necessary.
measure: Adverse events: line infections during Outpatient treatment
timeFrame: Start of treatment to up to 14 days post-treatment.
measure: Costs
timeFrame: Baseline (Randomization) to 90 days post-discharge
Other outcomes:
Locations:
Study officials:
affiliation: James A. Haley Veterans Administration Hospital
name: Ramona Gelzer Bell, MD
role: PRINCIPAL_INVESTIGATOR
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