Selective Cytopheretic Device (SCD) for heart and kidney failure patients awaiting LVAD

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 Worsening Renal Function Due to Cardiorenal Syndrome or Severe Right Ventricular Failure Awaiting Left Ventricular Assist Device Implantation

The Selective Cytopheretic Device (SCD) will be tried to reduce inflammation and help improve heart or kidney function in hospitalized patients with acute-on-chronic systolic heart failure and cardiorenal syndrome who are awaiting LVAD implantation.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: SeaStar Medical (Industry-sponsored)
• Drugs / interventions: radiation
• Locations: 1 site (Ann Arbor, Michigan)
• Trial ID: NCT03836482 on ClinicalTrials.gov

What this trial studies

This is a feasibility interventional protocol using an extracorporeal immunomodulatory membrane device (the SCD) in hospitalized patients with acute-on-chronic systolic heart failure and cardiorenal syndrome who are potential LVAD candidates. Eligible patients must show systemic inflammation (CRP ≥ 4.5 mg/L or IL-6 ≥ 5.0 pg/mL or neutrophil-to-lymphocyte ratio ≥ 3) and meet left ventricular ejection fraction and clinical criteria consistent with LVAD consideration. The device is intended to modulate the inflammatory state during hospitalization to try to improve cardiac or renal function and bridge patients to LVAD implantation. The protocol is sponsored by SeaStar Medical with collaborators including NHLBI and the University of Michigan and is conducted at the University of Michigan (Ann Arbor).

Who should consider this trial

Good fit: Hospitalized adults (≥18) with acute-on-chronic systolic heart failure and cardiorenal syndrome who have systemic inflammation (CRP ≥ 4.5 mg/L or IL-6 ≥ 5.0 pg/mL or NLR ≥ 3), reduced LVEF meeting LVAD consideration, and who are potential LVAD candidates.

Not a fit: Patients without systemic inflammation, with preserved left ventricular function, not considered for LVAD, or with contraindications to extracorporeal devices are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, the SCD could lower harmful inflammation to improve heart or kidney function and allow some patients previously deemed ineligible to become candidates for LVAD implantation.

How similar studies have performed: Small pilot studies of the SCD and related extracorporeal immunomodulatory approaches have reported preliminary safety and possible organ-function signals, but using the SCD specifically as a bridge to LVAD is novel and unproven.

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. Active 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.

Where this trial is running

Ann Arbor, Michigan

• University of Michigan — Ann Arbor, Michigan, United States (Recruiting)

Conditions Acute on Chronic Systolic Congestive Heart Failure; Cardiorenal Syndrome; Awaiting Left ventricular assist device implantation; Hospitalized; Selective Cytopheretic Device; SCD; LVAD; CRS