Selective Cytopheretic Device (SCD) Trial

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the selective cytopheretic device on the immune dysregulated state of congestive heart failure(CHF) with CRS and to assess the benefit of the device to improve cardiovascular and renal function. The study will enroll eligible patients in the ICU with acute on chronic systolic heart failure and worsening renal function due to cardiorenal syndrome while awaiting LVAD implantation. In this study patients who are eligible and agree to participate will receive treatment with the SCD. The treatment will be for 6 hours a day up to 6 days. Additionally, participants will have additional study procedures and be evaluated to determine if their kidney function improves enough to undergo LVAD implantation.

Official Title
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Pilot Study to Assess the Safety and Efficacy of a Selective Cytopheretic Device to Treat ICU Patients With Acute or Chronic Systolic Heart Failure With Cardiorenal Syndrome(CRS) Awaiting Left Ventricular Assist Device (LVAD) Implantation

Conditions
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Acute on Chronic Systolic Congestive Heart Failure, Cardiorenal Syndrome

Intervention / Treatment
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* Device: Selective Cytopheretic Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary hospitalization for acute decompensated chronic systolic heart failure Potential LVAD candidate with: Left ventricular ejection fraction ≤25% (for potential destination therapy) or ≤ 35% (for potential bridge to transplantation) as confirmed by baseline imaging procedure NYHA class IIIB or IV chronic (≤ 90 days) systolic heart failure, with failure to respond to optimal medical therapy (beta blocker, ACE inhibitor or ARB or valsartan/sacubitril, aldosterone antagonist, unless not tolerated or contraindicated, and loop diuretic, as needed) for 45 of the last 60 days Known previous peak exercise oxygen consumption < 14 mL/Kg/min or if unable to exercise, dependent on an intra-aortic balloon pump, short-term mechanical circulatory support device or intravenous inotropes unless inotropes contraindicated for clinical reasons (e.g., ventricular arrhythmias) Baseline eGFR** ≥ 40 ml/min/1.73 m2 (baseline defined as the highest known eGFR within 90 days of study enrollment) At least one of the following two criteria: Severe right ventricular failure (RVF), defined as meeting at least 2 of the following 4 criteria Central venous pressure > 16 mmHg Central venous pressure/Pulmonary wedge pressure >0.65 Right ventricular stroke work index < 300 mmHg * ml/m2 Pulmonary artery pulsatility index (PAPi) < 2, Worsening renal failure (WRF), defined for the purposes of this study as Increase serum creatinine ≥ 0.5 mg/dL from baseline (baseline defined as the lowest known serum creatinine within 90 days of study enrollment) AND eGFR** ≤ 30 ml/min/1.73 m2 based on serum creatinine at enrollment*** AND Cardiorenal syndrome is the most likely explanation for WRF AND Intolerant or inadequately responsive to standard of care diuretic therapy PA catheter in place at the time of enrollment PCW ≥ 20 mmHg Age ≥ 21and ≤ 75 years eGFR calculated using the 4-variable MDRD equation *** Recognizing that this is not a steady state creatinine Exclusion Criteria: Any clear contraindication to LVAD therapy that is unlikely to resolve with improvement in renal function and volume status Prior sensitivity to dialysis device components Bacteremia Temperature ≥ 101.5 F or WBC ≥ 10,000 K/uL or any patient with suspected systemic infection. Active malignancy requiring chemotherapy, biological therapy or radiation therapy The use of intravenous iodinated contrast agent within the prior 72 hours or the anticipated use of such an agent during SCD therapy Need for intravenous vasopressor (i.e., phenylephrine, vasopressin), intravenous vasoconstricting inotrope (i.e., norepinephrine or epinephrine) or dopamine > 3 mcg/kg/min. (Note: use of vasodilating inotropes [i.e., dobutamine and milrinone] or dopamine at ≤ 3 mcg/kg/min will not preclude study inclusion) Persistent SBP < 80 mmHg WBC < 4000 K/uL Platelets < 100,000K/uL Serum creatinine > 4 mg/dL or receiving dialysis / CRRT Acute coronary syndrome within the past month Women who are pregnant, breastfeeding a child, or trying to become pregnant Subject not able to sign informed consent, unless they have a legally authorized representative (LAR) Concurrent enrollment in another interventional clinical trial. Patients enrolled in clinical studies where only measurements and/or samples are taken (i.e., no test device or test drug used) are allowed to participate Use of any other investigational drug or device within the previous 30 days

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Selective Cytopheretic Device<br> | Device: Selective Cytopheretic Device<br>* Treatment will be delivered for 6 hours a day for up to 6 consecutive days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of patients with reversal of Worsening Renal Function (WRF) | WRF (≥ 0.5 mg/dL reduction of serum creatinine from level at study entry), and achieving an Estimated Glomerular Filtration Rate (eGFR) > 30 ml/min/1.73 m2 and Pulmonary Capillary Wedge (PCW) at or below level at study entry at termination of SCD therapy. | up to 30 days after the last SCD treatment or LVAD | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subject receiving a left ventricular assist device |  | up to 30 days after the last SCD | 
| Change in 24 hour urine volume |  | change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation | 
| Change in urine sodium |  | change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation | 
| Change in urine creatinine |  | change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation | 
| Change in urine urea |  | change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation | 
| Change in creatinine clearance |  | change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation | 
| Change in urine urea clearance |  | change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation | 
| Change in Pulmonary Capillary Wedge Pressure (PCWP) | If PCWP cannot be obtained, Pulmonary Artery Diastolic Pressure (PADP) will be used in its place. When utilizing PADP in place of PCWP for change measures, comparisons will be made to baseline PADP. | change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation | 
| Change in serum sodium |  | change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation | 
| Change in serum potassium |  | change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation | 
| Change in serum dissolved carbon dioxide (CO2) |  | change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation | 
| Change in blood urea nitrogen (BUN) |  | change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation | 
| Change in serum creatinine |  | change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation | 
| Percentage of subjects with reduction of serum creatinine (≥ 0.5 mg/dL) and PCWP (≤ 18 mmHg) | If PCWP cannot be obtained, PADP will be used in its place. When utilizing PADP in place of PCWP for change measures, comparisons will be made to baseline PADP | change from onset of intervention to 3 and 6 days after initiation of SCD treatments and from onset of intervention to end of SCD support prior to LVAD implantation | 
| Percentage of subjects receiving a left ventricular assist device with serum creatinine ≥ 0.5 mg/dL below level at study entry |  | 30 days following discontinuation of SCD | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Awaiting Left ventricular assist device implantation, Hospitalized