<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03836482</url>
  </required_header>
  <id_info>
    <org_study_id>HUM00143014</org_study_id>
    <nct_id>NCT03836482</nct_id>
  </id_info>
  <brief_title>Selective Cytopheretic Device (SCD) Trial</brief_title>
  <official_title>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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Keith Aaronson, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Michigan</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the selective cytopheretic device on the immune&#xD;
      dysregulated state of congestive heart failure(CHF) with CRS and to assess the benefit of the&#xD;
      device to improve cardiovascular and renal function. The study will enroll eligible patients&#xD;
      in the ICU with acute on chronic systolic heart failure and worsening renal function due to&#xD;
      cardiorenal syndrome while awaiting LVAD implantation.&#xD;
&#xD;
      In this study patients who are eligible and agree to participate will receive treatment with&#xD;
      the SCD. The treatment will be for 6 hours a day up to 6 days. Additionally, participants&#xD;
      will have additional study procedures and be evaluated to determine if their kidney function&#xD;
      improves enough to undergo LVAD implantation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    Study halted temporarily to obtain protocol amendment approval but potentially will resume.&#xD;
  </why_stopped>
  <start_date type="Actual">November 11, 2019</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Anticipated">February 2025</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent of patients with reversal of Worsening Renal Function (WRF)</measure>
    <time_frame>up to 30 days after the last SCD treatment or LVAD</time_frame>
    <description>WRF (≥ 0.5 mg/dL reduction of serum creatinine from level at study entry), and achieving an Estimated Glomerular Filtration Rate (eGFR) &gt; 30 ml/min/1.73 m2 and Pulmonary Capillary Wedge (PCW) at or below level at study entry at termination of SCD therapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of subject receiving a left ventricular assist device</measure>
    <time_frame>up to 30 days after the last SCD</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in 24 hour urine volume</measure>
    <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</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in urine sodium</measure>
    <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</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in urine creatinine</measure>
    <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</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in urine urea</measure>
    <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</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in creatinine clearance</measure>
    <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</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in urine urea clearance</measure>
    <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</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Pulmonary Capillary Wedge Pressure (PCWP)</measure>
    <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</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum sodium</measure>
    <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</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum potassium</measure>
    <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</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum dissolved carbon dioxide (CO2)</measure>
    <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</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in blood urea nitrogen (BUN)</measure>
    <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</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum creatinine</measure>
    <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</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects with reduction of serum creatinine (≥ 0.5 mg/dL) and PCWP (≤ 18 mmHg)</measure>
    <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</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of subjects receiving a left ventricular assist device with serum creatinine ≥ 0.5 mg/dL below level at study entry</measure>
    <time_frame>30 days following discontinuation of SCD</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Acute on Chronic Systolic Congestive Heart Failure</condition>
  <condition>Cardiorenal Syndrome</condition>
  <arm_group>
    <arm_group_label>Selective Cytopheretic Device</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Selective Cytopheretic Device</intervention_name>
    <description>Treatment will be delivered for 6 hours a day for up to 6 consecutive days.</description>
    <arm_group_label>Selective Cytopheretic Device</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Primary hospitalization for acute decompensated chronic systolic heart failure&#xD;
&#xD;
          2. Potential LVAD candidate with:&#xD;
&#xD;
               1. Left ventricular ejection fraction ≤25% (for potential destination therapy) or ≤&#xD;
                  35% (for potential bridge to transplantation) as confirmed by baseline imaging&#xD;
                  procedure&#xD;
&#xD;
               2. NYHA class IIIB or IV chronic (≤ 90 days) systolic heart failure, with failure to&#xD;
                  respond to optimal medical therapy (beta blocker, ACE inhibitor or ARB or&#xD;
                  valsartan/sacubitril, aldosterone antagonist, unless not tolerated or&#xD;
                  contraindicated, and loop diuretic, as needed) for 45 of the last 60 days&#xD;
&#xD;
               3. Known previous peak exercise oxygen consumption &lt; 14 mL/Kg/min or if unable to&#xD;
                  exercise, dependent on an intra-aortic balloon pump, short-term mechanical&#xD;
                  circulatory support device or intravenous inotropes unless inotropes&#xD;
                  contraindicated for clinical reasons (e.g., ventricular arrhythmias)&#xD;
&#xD;
          3. Baseline eGFR** ≥ 40 ml/min/1.73 m2 (baseline defined as the highest known eGFR within&#xD;
             90 days of study enrollment)&#xD;
&#xD;
          4. At least one of the following two criteria:&#xD;
&#xD;
               1. Severe right ventricular failure (RVF), defined as meeting at least 2 of the&#xD;
                  following 4 criteria&#xD;
&#xD;
                    -  Central venous pressure &gt; 16 mmHg&#xD;
&#xD;
                    -  Central venous pressure/Pulmonary wedge pressure &gt;0.65&#xD;
&#xD;
                    -  Right ventricular stroke work index &lt; 300 mmHg * ml/m2&#xD;
&#xD;
                    -  Pulmonary artery pulsatility index (PAPi) &lt; 2,&#xD;
&#xD;
               2. Worsening renal failure (WRF), defined for the purposes of this study as&#xD;
&#xD;
                    -  Increase serum creatinine ≥ 0.5 mg/dL from baseline (baseline defined as the&#xD;
                       lowest known serum creatinine within 90 days of study enrollment) AND&#xD;
&#xD;
                    -  eGFR** ≤ 30 ml/min/1.73 m2 based on serum creatinine at enrollment*** AND&#xD;
&#xD;
                    -  Cardiorenal syndrome is the most likely explanation for WRF AND&#xD;
&#xD;
                    -  Intolerant or inadequately responsive to standard of care diuretic therapy&#xD;
&#xD;
          5. PA catheter in place at the time of enrollment&#xD;
&#xD;
          6. PCW ≥ 20 mmHg&#xD;
&#xD;
          7. Age ≥ 21and ≤ 75 years&#xD;
&#xD;
               -  eGFR calculated using the 4-variable MDRD equation *** Recognizing that this is&#xD;
                  not a steady state creatinine&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any clear contraindication to LVAD therapy that is unlikely to resolve with&#xD;
             improvement in renal function and volume status&#xD;
&#xD;
          2. Prior sensitivity to dialysis device components&#xD;
&#xD;
          3. Bacteremia&#xD;
&#xD;
          4. Temperature ≥ 101.5 F or WBC ≥ 10,000 K/uL or any patient with suspected systemic&#xD;
             infection.&#xD;
&#xD;
          5. Active malignancy requiring chemotherapy, biological therapy or radiation therapy&#xD;
&#xD;
          6. The use of intravenous iodinated contrast agent within the prior 72 hours or the&#xD;
             anticipated use of such an agent during SCD therapy&#xD;
&#xD;
          7. Need for intravenous vasopressor (i.e., phenylephrine, vasopressin), intravenous&#xD;
             vasoconstricting inotrope (i.e., norepinephrine or epinephrine) or dopamine &gt; 3&#xD;
             mcg/kg/min. (Note: use of vasodilating inotropes [i.e., dobutamine and milrinone] or&#xD;
             dopamine at ≤ 3 mcg/kg/min will not preclude study inclusion)&#xD;
&#xD;
          8. Persistent SBP &lt; 80 mmHg&#xD;
&#xD;
          9. WBC &lt; 4000 K/uL&#xD;
&#xD;
         10. Platelets &lt; 100,000K/uL&#xD;
&#xD;
         11. Serum creatinine &gt; 4 mg/dL or receiving dialysis / CRRT&#xD;
&#xD;
         12. Acute coronary syndrome within the past month&#xD;
&#xD;
         13. Women who are pregnant, breastfeeding a child, or trying to become pregnant&#xD;
&#xD;
         14. Subject not able to sign informed consent, unless they have a legally authorized&#xD;
             representative (LAR)&#xD;
&#xD;
         15. Concurrent enrollment in another interventional clinical trial. Patients enrolled in&#xD;
             clinical studies where only measurements and/or samples are taken (i.e., no test&#xD;
             device or test drug used) are allowed to participate&#xD;
&#xD;
         16. Use of any other investigational drug or device within the previous 30 days&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Keith Aaronson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>February 7, 2019</study_first_submitted>
  <study_first_submitted_qc>February 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <last_update_submitted>April 21, 2023</last_update_submitted>
  <last_update_submitted_qc>April 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>Keith Aaronson, MD</investigator_full_name>
    <investigator_title>Collegiate Professor of Cardiovascular Medicine and Professor of Internal Medicine</investigator_title>
  </responsible_party>
  <keyword>Awaiting Left ventricular assist device implantation</keyword>
  <keyword>Hospitalized</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardio-Renal Syndrome</mesh_term>
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Systolic Murmurs</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03836482
org study id: HUM00143014
nct id: NCT03836482
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percent of patients with reversal of Worsening Renal Function (WRF)
time frame: up to 30 days after the last SCD treatment or LVAD
description: 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.
measure: Percentage of subject receiving a left ventricular assist device
time frame: up to 30 days after the last SCD
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: Change in Pulmonary Capillary Wedge Pressure (PCWP)
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
description: 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.
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: Percentage of subjects with reduction of serum creatinine (≥ 0.5 mg/dL) and PCWP (≤ 18 mmHg)
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
description: 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
measure: 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
arm group label: Selective Cytopheretic Device
arm group type: Experimental
intervention type: Device
intervention name: Selective Cytopheretic Device
description: Treatment will be delivered for 6 hours a day for up to 6 consecutive days.
arm group label: Selective Cytopheretic Device
criteria: 
gender: All
minimum age: 21 Years
maximum age: 75 Years
healthy volunteers: No
last name: Keith Aaronson, MD
role: Principal Investigator
affiliation: University of Michigan
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Michigan
investigator full name: Keith Aaronson, MD
investigator title: Collegiate Professor of Cardiovascular Medicine and Professor of Internal Medicine
mesh term: Cardio-Renal Syndrome
mesh term: Heart Failure
mesh term: Syndrome
mesh term: Systolic Murmurs
sharing ipd: No