Selective Cytopheretic Device (SCD) Trial

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

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.

Study Overview

• Status: Suspended
• Conditions: Cardiorenal Syndrome; Acute on Chronic Systolic Congestive Heart Failure
• Intervention / Treatment: Device: Selective Cytopheretic Device

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Angela Westover, BS; Phone Number: 734-936-6467; Email: funke@med.umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Primary hospitalization for acute decompensated chronic systolic heart failure

2. Potential LVAD candidate with:

   1. Left ventricular ejection fraction ≤25% (for potential destination therapy) or ≤ 35% (for potential bridge to transplantation) as confirmed by baseline imaging procedure
   2. 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
   3. 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)
3. Baseline eGFR** ≥ 40 ml/min/1.73 m2 (baseline defined as the highest known eGFR within 90 days of study enrollment)

4. 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
5. PA catheter in place at the time of enrollment
6. PCW ≥ 20 mmHg

7. Age ≥ 21and ≤ 75 years

   • eGFR calculated using the 4-variable MDRD 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. Active malignancy requiring chemotherapy, biological therapy or radiation therapy
6. The use of intravenous iodinated contrast agent within the prior 72 hours or the anticipated use of such an agent during SCD therapy
7. 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)
8. Persistent SBP < 80 mmHg
9. WBC < 4000 K/uL
10. Platelets < 100,000K/uL
11. Serum creatinine > 4 mg/dL or receiving dialysis / CRRT
12. Acute coronary syndrome within the past month
13. Women who are pregnant, breastfeeding a child, or trying to become pregnant
14. Subject not able to sign informed consent, unless they have a legally authorized representative (LAR)
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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Selective Cytopheretic Device	Device: Selective Cytopheretic Device; Treatment will be delivered for 6 hours a day for up to 6 consecutive days.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Lenar Yessayan
• Investigators: Principal Investigator: Keith Aaronson, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2019
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: February 7, 2019
• First Submitted That Met QC Criteria: February 7, 2019
• First Posted (Actual): February 11, 2019

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 16, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Hospitalized; Awaiting Left ventricular assist device implantation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Disease; Renal Insufficiency; Heart Murmurs; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Heart Failure; Syndrome; Systolic Murmurs; Cardio-Renal Syndrome
• Other Study ID Numbers: HUM00143014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes