Clinical trial NCT03836482: Feasibility of the SCD in Cardiorenal Syndrome Patients Awaiting LVAD
Official title: Feasibility Study to Assess the Safety and Efficacy of a Selective Cytopheretic Device (SCD) to Treat ICU Patients With Acute on Chronic Systolic Heart Failure With Cardiorenal Syndrome Awaiting Left Ventricular Assist Device Implantation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Acute on Chronic Systolic Congestive Heart Failure
Cardiorenal Syndrome
Keywords: Awaiting Left ventricular assist device implantation
Hospitalized
Selective Cytopheretic Device
SCD
LVAD
CRS
Lead sponsor: SeaStar Medical
Sponsor class: INDUSTRY
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: University of Michigan
name: Innovative BioTherapies (IBT)
First posted: 2019-02-11
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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 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 6 days, followed by 6 months of follow up.


Eligibility criteria: Inclusion Criteria:

1. Age of 18 years and older.
2. Evidence of systemic inflammation: blood CRP ≥ 4.5 mg/L or IL-6 ≥ 5.0 pg/ml or neutrophil to lymphocyte ratio ≥3.0.
3. Primary hospitalization for acute decompensated chronic systolic heart failure.
4. Potential LVAD candidate with:

   a) Left ventricular ejection fraction ≤25% (for potential destination therapy) or ≤ 35% (for potential bridge to transplantation) as confirmed by baseline imaging procedure b) 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, SGLT2i, unless not tolerated or contraindicated, and loop diuretic, as needed) for 45 of the last 60 days c) 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)
5. Baseline eGFR\*\* ≥ 40 ml/min/1.73 m2 (baseline defined as the highest known eGFR within 90 days of study enrollment)
6. At least one of the following two criteria:

   1. 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,
   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, defined as persistent signs and/or symptoms of congestion (e.g., peripheral edema, dyspnea, pulmonary rales, neck vein distension) or minimal net volume removal in a 24-hour period despite optimal medical therapy including intravenous diuretic therapy and an estimated need for \>5kg fluid removal.

        1. Optimal intravenous diuretic therapy is defined as:

           1. Furosemide equivalent total daily dose of 240mg
           2. Furosemide equivalent dose given either as a single or multiple intravenous bolus or continuous infusion
           3. A furosemide equivalent total daily dose \<240mg if the dose has resulted in \>3000 mL urine output/24 hours.
7. PA catheter in place at the time of enrollment
8. PCW ≥ 20 mmHg

   * eGFR calculated using the CKD-EPI Creatinine Equation \*\*\* Recognizing that this is not a steady state creatinine

Exclusion Criteria:

1. Any clear contraindication to LVAD therapy that is unlikely to resolve with improvement in renal function and volume status
2. Prior sensitivity to dialysis device components
3. Bacteremia
4. Temperature ≥ 101.5 F or WBC ≥ 10,000 K/uL or any patient with suspected systemic infection.
5. Metastatic malignancy requiring palliative chemo, biologic, or radiation
6. 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)
7. Patients requiring mechanical ventilatory support
8. Patients requiring total parenteral nutrition during the treatment period
9. Persistent SBP \< 80 mmHg
10. WBC \< 4000 K/uL
11. Platelets \< 100,000K/uL
12. Serum creatinine \> 4 mg/dL or receiving dialysis / CRRT
13. Acute coronary syndrome within the past month
14. Women who are pregnant, breastfeeding a child, or trying to become pregnant
15. 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
16. Use of any other investigational drug or device within the previous 30 days. Patients who participated in a clinical study where only measurements and/or samples are taken (i.e., no test device or drug used) are allowed to participate.

Primary outcomes:
measure: Need for continuous IV vasopressor support
timeFrame: measured daily, at or after 4 hours after termination of daily SCD therapy
measure: Acute myocardial infarction
timeFrame: up to 6 months following SCD treatment initiation
measure: Mortality
timeFrame: up to 6 months following SCD treatment initiation
measure: Percentage of subjects with reversal of WRF and increase eGFR and PCW
timeFrame: up to 6 days after initiation of SCD therapy
Secondary outcomes:
measure: Percentage of subject receiving a left ventricular assist device
timeFrame: up to 30 days after the last SCD
measure: Change in 24 hour urine volume
timeFrame: 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
measure: Change in urine sodium
timeFrame: 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
measure: Change in urine creatinine
timeFrame: 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
measure: Change in urine urea
timeFrame: 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
measure: Change in creatinine clearance
timeFrame: 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
measure: Change in urine urea clearance
timeFrame: 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
measure: Change in Pulmonary Capillary Wedge Pressure (PCWP)
timeFrame: 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
measure: Change in serum sodium
timeFrame: 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
measure: Change in serum potassium
timeFrame: 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
measure: Change in serum dissolved carbon dioxide (CO2)
timeFrame: 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
measure: Change in blood urea nitrogen (BUN)
timeFrame: 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
measure: Change in serum creatinine
timeFrame: 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
measure: Percentage of subjects with reduction of serum creatinine (≥ 0.5 mg/dL) and PCWP (≤ 18 mmHg)
timeFrame: 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
measure: Percentage of subjects receiving a left ventricular assist device with serum creatinine ≥ 0.5 mg/dL below level at study entry
timeFrame: 30 days following discontinuation of SCD
measure: Change in right ventricular fractional area change
timeFrame: 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
Other outcomes:
Locations:
Study officials:
References: