Cardiovascular disease is the leading cause of mortality in the US, accounting for 45% of all deaths. Chronic Heart Failure (CHF) is now understood to be a multi-system disease process involving not only the cardiovascular system but also the renal, neuroendocrine, and immune systems. No effective therapy is currently available to treat the most severe subset of CHF patients that have progressed to acute decompensated HF. An innovative approach to reduce the cardio-depressant effects associated with the chronic inflammatory state of CHF may provide a breakthrough for this disorder. This proposal will evaluate the safety and probable benefit to improve cardiac or renal function with an immunomodulatory device to bridge patients to Left Ventricular Assist Device (LVAD) implantation who were previously deemed ineligible for this life sustaining procedure. The Selective Cytopheretic Device (SCD) is an immuno-regulating, extracorporeal membrane device targeted to modulate the cardiodepressant effects assocaited with CHF. SCD is a platform technology focused on immunomodulation of acute and chronic inflammation associated with acute and chronic organ dysfunction. SCD membranes selectively sequester activated systemic leukocytes as they flow through the cartridge via an extracorporeal circuit. Pre-clinical results show that SCD treatment results in a 25% improvement in ejection fraction in a canine CHF model. This study will enroll 20 patients across up to 5 clinical sites to evaluate the safety and initial efficacy data of SCD treatment in this indication. Patients will receive 4-hour daily SCD treatment for up to 6 days, followed by 6 months of follow up.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Treatment will be delivered for 4 hours a day for up to 6 consecutive days.
Need for continuous IV vasopressor support
Need for continuous IV vasopressor support with \>5 total norepinephrine equivalents and/or \>3 vasopressor agents \>4 hours following termination of daily SCD therapy session to maintain a MAP \>60 mmHg, with norepinephrine equivalents defined as: 1. 1 x epinephrine (ug/kg/min) 2. 001 x dopamine (ug/kg/min) 3. 0.06 x phenylephrine (ug/kg/min) 4. 2.5 x vasopressin (U/min) (Note that use of inotropes (i.e., dobutamine and milrinone) or dopamine at ≤3 mcg/kg/min are not components of this measure.)
Time frame: measured daily, at or after 4 hours after termination of daily SCD therapy
Acute myocardial infarction
Acute myocardial infarction as evidenced by elevated cardiac enzymes, with electrocardiographic or imaging findings consistent with myocardial damage and confirmed by Cardiology.
Time frame: up to 6 months following SCD treatment initiation
Mortality
Death
Time frame: up to 6 months following SCD treatment initiation
Percentage of subjects with reversal of WRF and increase eGFR and PCW
Among patients with WRF, the percentage of subjects with reversal of WRF (≥ 0.5 mg/dL reduction of serum creatinine from level at study entry), and achieving an eGFR \> 30 ml/min/1.73 m2 and PCWP at or below level at study entry at termination of SCD therapy.
Time frame: up to 6 days after initiation of SCD therapy
Percentage of subjects who no longer have severe right ventricular failure
Among subjects with severe RVF, the percentage of subjects who no longer have severe right ventricular failure, as evidenced by absence of 3 or more of the following 4 indicators of right ventricular failure: 1. CVP \> 16 mmHg 2. CVP/PCWP \> 0.65 3. RVSWI \< 300 mmHg \* mL/m 4. PAPi \< 2
Time frame: up to 6 days after initiation of SCD therapy
Adverse Events
Adverse Events due to SCD, hemodialysis catheter, KRT pump, circuit, and hemofilter
Time frame: up to 6 days after initiation of SCD therapy
Percentage of subject receiving a left ventricular assist device
Time frame: up to 30 days after the last SCD
Change in 24 hour urine volume
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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
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Change in serum sodium
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 30 days following discontinuation of SCD
Change in right ventricular fractional area change
Change in right ventricular fractional area change, TAPSE, and right ventricular global longitudinal strain
Time frame: 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