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.

Aquapheresis Efficacy in Outpatients With Decompensated Heart Failure

Heart Failure

Congestive Heart Failure

Decompensated Heart Failure

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.

Aquapheresis

IV Diuretics

Efficacy of Aquapheresis in Patients Treated as Outpatients With Decompensated Heart Failure at a Veterans Hospital

Compare number of hospitalization readmissions for CHF between Intervention (Aquaphersis arm) & Control groups

Compare weight change (pounds) in patients between Intervention & Control groups

Director Congestive Heart Failure Program

Compare total fluid removal (ml) in patients between Intervention & Control groups

Compare Blood urea nitrogen (BUN; mg/dl) (higher than normal range is worse) in patients between Intervention & Control groups

Compare Blood urea nitrogen (BUN; mg/dl) (higher than normal range is worse)) in patients between Intervention & Control groups

Compare Creatinine (Cr; mg/dl) (higher than normal range is worse) in patients between Intervention & Control groups

Compare Glomerular filtration rate (GFR; ml/min/1.73 meters squared) (lower than normal range is worse) in patients between Intervention & Control groups

Compare BNP (pg/ml of blood) (higher than normal range is worse) in patients between Intervention & Control groups

Compare 6-minute Walk Test (meters/6 minutes; less distance means more disability) in patients between Intervention & Control groups

Compare Minnesota Living with Heart Failure Questionnaire (MLWHFQ) (total score; higher score means more impairment) in patients between Intervention & Control groups

Compare SF-36 weighted sums (0-100 scale; lower score means more disability) in patients between Intervention & Control groups

Compare number of Adverse Events (bleeding incidents) in patients between Intervention & Control groups: bleeding, line-related infection, etc.

Compare number of Adverse Events (line infections) in patients between Intervention & Control groups: bleeding, line-related infection, etc.

Compare costs (dollars) between Intervention & Control groups

Per protocol, if randomized to Aquapheresis arm (AQ), all diuretics are discontinued and AQ will be administered as per established protocol. BMP and CBC will be checked prior to initiation and as needed, 7-10 days, 30, 60 and 90 days post discharge. Note, aquapheresis rate is to be decreased by 100 cc/hr if Hgb increases by 1gm/dL, and stopped if rate is decreased to 50 cc/hr or reaches euvolemia, whichever comes first.

Per protocol (Fig 2), if randomized to IV diuretic therapy arm (IV), the patient will receive initial dose of IV diuretic based on base line renal function; then the dose will be doubled every 2 hrs if refractory, to a maximum of 8mg IV Bumex (or 320mg IV Lasix). Metolazone may be added at 2.5mg PO 30 minutes before loop diuretic if CR< 2.0, or 5mg PO if Cr > 2.0, if refractory to high dose loop diuretic. If a patient in IV arm is refractory to maximum 320 mg IV Lasix or 8 mg IV Bumex plus Metolazone then the patient may cross over to AQ arm.

Aquapheresis Efficacy in Outpatients With Decompensated Heart Failure

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Trial Timing

What is this trial about?

What are the Participation Requirements?