<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/NCT03808948</url>
  </required_header>
  <id_info>
    <org_study_id>EmPaKt-CHF</org_study_id>
    <secondary_id>2018-002638-18</secondary_id>
    <nct_id>NCT03808948</nct_id>
  </id_info>
  <brief_title>FAST PV and mGFR™ Technology in Congestive Heart Failure</brief_title>
  <official_title>Estimating Versus Measuring Plasma Volume and Kidney Function in Acute Decompensated Congestive Heart Failure (EMPaKT-CHF)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Charite University, Berlin, Germany</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>FAST BioMedical</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Charite University, Berlin, Germany</source>
  <oversight_info>
    <has_dmc>No</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>
      This is an investigator-initiated, one-armed, phase 2 clinical trial using an injectable&#xD;
      fluorescent tracer to assay and evaluate measured plasma volume (mPV) and measured glomerular&#xD;
      filtration rate (mGFR) in hospitalized patients with acute decompensated congestive heart&#xD;
      failure (CHF).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This investigator-initiated, one-armed study is designed to evaluate the safety and function&#xD;
      of the FAST PV and mGFR Technology in patients with CHF. Data from the FAST PV and mGFR&#xD;
      Technology will not be evaluable by the treating physician, but will be made available to the&#xD;
      study investigators and to an adjudication committee.&#xD;
&#xD;
      Patients enrolled in the study will be administered the VFI (Day 1) and with a second dose&#xD;
      occurring 24-48 hours after the initial dose (Day 3).&#xD;
&#xD;
      After consenting to be enrolled in the study, patients meeting the enrollment criteria will&#xD;
      receive a single dose of two component VFI. Blood draws (3 mL) will be collected pre-dose and&#xD;
      at 15, 30, 60, and 180 minutes post-dose, which will be subsequently used to determine the&#xD;
      patient's blood volume and mGFR using the FAST PV and mGFR Technology. Patients will be&#xD;
      treated according to standard of care throughout the time of their hospitalization. A second&#xD;
      dose of VFI will be administered 48 (+/- 5) hours after the initial dosing. Again, blood&#xD;
      draws (3 mL) will be collected pre-dose and at 15, 30, 60, and 180 minutes post-dose. Plasma&#xD;
      volume (PV) was determined using the average concentrations of the higher molecular marker of&#xD;
      VFI of the early 15 min and the 60 min time point. The concentration of the small dextran GFR&#xD;
      marker at time zero was back calculated from the measured PV by dividing the known dose into&#xD;
      the measured PV. The time points were then fitted using atwo-compartment model and the&#xD;
      resulting area under the curve was calculated. The use of the time point 0 determination&#xD;
      helped to better resolve the shape of the clearance curve.&#xD;
&#xD;
      Study-related blood samples will be obtained on days 1, 2, 3, 4, and 5 to measure serum&#xD;
      creatinine (days 1-5), hematocrit (days 1, 3), and N-terminal pro-brain natriuretic peptide&#xD;
      (NT-pro-BNP), creatine phosphokinase (CPK), alanine aminotransferase (ALT), aspartate&#xD;
      aminotransferase (AST), alkaline phosphatase, bilirubin total and direct, and international&#xD;
      normalized ratio (INR) (days 1, 3, and 5); and will be stored for future testing of&#xD;
      additional parameters in the research fields of acute decompensated heart failure and acute&#xD;
      kidney injury.&#xD;
&#xD;
      The available laboratory values will be entered in the Dosing Day Case Report Form (CRF),&#xD;
      along with any copies of physician's notes and orders entered that day. Prior to&#xD;
      administering the first and second dose of VFI, the physician will be asked to complete a&#xD;
      very brief survey to provide a qualitative assessment of the patient's perceived volume&#xD;
      status and renal function prior to initiating the FAST PV and mGFR measurements.&#xD;
&#xD;
      Laboratory values and assessments will be captured on each day that the VFI is administered,&#xD;
      and these data will be entered into the CRF. Any adverse events (AEs) determined by the&#xD;
      investigator to be related or possibly related to the VFI will be captured. Patients will&#xD;
      receive a followup phone call 7 days (± 2 days) after the first dose of VFI was administered,&#xD;
      and a second follow up call 30 days after the first dose of VFI was administered as an end of&#xD;
      study (EOS) follow up call. Any AEs determined by the investigator will be captured during&#xD;
      the follow up calls and will be followed to resolution. Additionally, in-person follow-up&#xD;
      visits may be scheduled as needed.&#xD;
&#xD;
      Upon conclusion of the study, the recorded clinical data will be provided to an independent&#xD;
      data adjudication committee (DAC) in a pseudonymized fashion. The DAC will be asked to review&#xD;
      the available data at the time of the first dosing, and the measured GFR and PV data for the&#xD;
      first dosing day will be provided. The DAC will then be asked to fill out a survey asking&#xD;
      whether the mGFR and PV data would have influenced their treatment decision, and if so,&#xD;
      indicate what they would have done differently.&#xD;
&#xD;
      Following the evaluation of mGFR and PV data at the time of the initial VFI dose, the mGFR&#xD;
      and PV data determined from the second VFI dosing point will be provided to the DAC. The DAC&#xD;
      will then be asked to fill out a separate survey asking how the actual measured PV and GFR&#xD;
      differ from the clinical assessments, whether the mGFR and PV data would influence their&#xD;
      treatment decision, and if so, indicate what they would have done differently.&#xD;
&#xD;
      After all assessments have been completed, the DAC will review the results of their analyses&#xD;
      and compile a summary report on the secondary endpoints as well as their assessment of the&#xD;
      overall impact of the PV and mGFR on clinical decision making.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 10, 2019</start_date>
  <completion_date type="Actual">August 17, 2019</completion_date>
  <primary_completion_date type="Actual">August 17, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Treatment Related AEs and Serious Adverse Events (SAEs)</measure>
    <time_frame>30 days</time_frame>
    <description>The percentage of treatment emergent SAEs considered to be surely related to the VFI should be zero.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage Difference in Mean Plasma Concentration of FD003 Over the 15-, 30-, and 60-minute Blood Draws on Days 1 and 3</measure>
    <time_frame>3 days</time_frame>
    <description>Function of the FAST PV measurement will be assessed by determining the plasma stability of the FD003 high molecular weight marker over the 15, 30, and 60 minute blood draws and applying the following criteria:&#xD;
The FAST PV measurement is considered as stable, if the mean plasma concentration of FD003 at 30 minutes is not more than 10% lower than the mean plasma concentration at 15 minutes AND if the mean plasma concentration at 60 minutes is not more than 10% lower than the mean plasma concentration at 30 minutes&#xD;
We will determine the percentage of patients which show a decline in the plasma concentration of FD003 of more than 10% from 15min to 30min and separately from 30 min to 60min. This percentage should be ideally close to 0.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Accuracy Between Estimated PV (ePV) on Days 1 and 3 (by Established Measures) and Measured PV (mPV; as Assessed by FAST Methodology) Defined as the Percentage of the Population With a &lt;15% and &lt;30% Difference Between ePV and mPV</measure>
    <time_frame>3 days</time_frame>
    <description>The percentage difference between ePV and mPV were evaluated to consider the percentage of the population with a &lt;15% and &lt;30% difference between ePV and mPV on day 1 and day 3</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accuracy Between Estimated Total Blood Volume (TBV) on Days 1 and 3 and Measured TBV (mTBV; Calculated From mPV and Measured Hematocrit) Defined as the Percentage of the Population With a &lt;15% and &lt;30% Difference Between ePV and mPV</measure>
    <time_frame>3 days</time_frame>
    <description>Accuracy between the Nadler's Formula as an estimate of total blood volume (TBV) and measured blood volume (mTBV) on days 1 and 3 as determined by the percentage of the population with a &lt;15% and &lt;30% difference between ePV and mPV</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accuracy of eGFR Determined by CKD-EPI-SCr and mGFR on Day 1 and Day 3 Defined the Percentage of the Population With a &lt;15% and &lt;30% Difference Between eGFR and mGFR</measure>
    <time_frame>3 days</time_frame>
    <description>To evaluate whether estimated Glomerular Filtration Rate (eGFR) (calculation by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula) on days 1 and 3 provides an accurate estimate of measured GFR (mGFR; assessed by FAST methodology) in heart failure patients under-going active fluid management, determined by the percentage of patients with a &lt;15% and &lt;30% difference between eGFR and mGFR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of the Population That Developed Acute Kidney Injury (AKI) Within the Following 48-72 Hour and Prediction of AKI by mGFR/eGFR Ratio on Days 1 and 3</measure>
    <time_frame>48-72h</time_frame>
    <description>To evaluate the percentage of patients developing acute kidney injury (AKI) within the following 48-72 hours on day 1 and day 3 and to evaluate whether patients with a low mGFR/eGFR ratio on days 1 and 3 are at higher risk of developing acute kidney injury (AKI) within the following 48-72 hours using a binary logisitic regression with AKI as binary outcome and mGFR/eGFR as independent variate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients Who Are Refractory to Diuretic Therapy</measure>
    <time_frame>5 days</time_frame>
    <description>Being refractory to diuretic therapy (defined as any dosage increases of furosemide i.v. dose equivalent, adding thiazide after day 1, requirement of ultrafiltration/RRT within the next 24-48 hours, failure to improve subjectively in PGA and dyspnoea scales, failure of mean weight loss during the study period Day 1-Day 5 of at least 0,5 kg/d).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Population in Which Clinical Decision Making Would Have Been Influenced by Adding FAST GFR and PV Measurements to Clinical Routine Determined by Survey Response (by an Adjudication Committee)</measure>
    <time_frame>3 days</time_frame>
    <description>Percentage of patients for whom the data decision committee decided to increase or decrease the dose of diuretics, guideline-directed medical therapy (GDMT), beta-blockers, or RAAS inhibitors from the dose indicated by the treating physician after considering the mPV/mTBV determined using FAST BioMedical technology.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>CHF</condition>
  <arm_group>
    <arm_group_label>All Patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>VFI dose: 47 mg / 3 mL Number of doses: 2 Route of administration: intravenous</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>VFI</intervention_name>
    <description>The IV-administered visible fluorescent injectate (VFI)™ agent comprises a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.</description>
    <arm_group_label>All Patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent indicating an understanding of the purpose of and procedures&#xD;
             required for the study and willingness to participate in the study prior to any&#xD;
             study-related measures present.&#xD;
&#xD;
          -  Hospitalized patient with acute decompensated heart failure, diagnosed on the basis of&#xD;
             the presence of at least one symptom (dyspnea, orthopnea, or edema) and one sign&#xD;
             (rales, peripheral edema, ascites, or pulmonary vascular congestion on chest&#xD;
             radiography) of heart failure.&#xD;
&#xD;
          -  ≥ 18 years of age.&#xD;
&#xD;
          -  Male with female partners of childbearing potential give agreement to practice&#xD;
             abstinence or use condoms from enrollment through 90 days after administration of the&#xD;
             last dose of study drug present.&#xD;
&#xD;
          -  Partner of a male patient: Agreement to use a medically acceptable method of&#xD;
             contraception (a barrier method, intrauterine device, or hormonal contraception) from&#xD;
             enrollment through 90 days after administration of the last dose of study drug&#xD;
             present.&#xD;
&#xD;
          -  Male patient agrees to not donate sperm from enrollment through 90 days after&#xD;
             administration of the last dose of study drug present.&#xD;
&#xD;
          -  A female patient is eligible to enter the study if she is not pregnant or nursing; of&#xD;
             non-childbearing potential (ie, post-menopausal defined as having been amenorrheic for&#xD;
             at least 1 year prior to screening, or has had bilateral tubal ligation at least 6&#xD;
             months prior to administration of study drug or bilateral oophorectomy or complete&#xD;
             hysterectomy); and if of childbearing potential, must have a negative urine or serum&#xD;
             pregnancy test within 24 h prior to drug administration and be using a highly&#xD;
             effective means of contraception during study participation and until 1 month after&#xD;
             the last dose of study drug. Highly effective contraception methods include total&#xD;
             abstinence or combination of any two of the following: (i) use of oral, injected, or&#xD;
             implanted hormonal methods of contraception or other forms of hormonal contraception&#xD;
             that have comparable efficacy; (ii) placement of an intrauterine device (IUD) or&#xD;
             intrauterine system (IUS); and (iii) barrier methods of contraception: condom or&#xD;
             occlusive cap (diaphragm or cervical/vault caps). In case of use of oral&#xD;
             contraception, women should have been stable on the same pill for a minimum of 3&#xD;
             months before taking study treatment.&#xD;
&#xD;
          -  Patient is able to communicate effectively with the study personnel.&#xD;
&#xD;
          -  Patient is informed of the nature and risks of the study and give written informed&#xD;
             consent prior to enrollment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  New or ongoing myocardial infarction or unstable angina present at the time of planned&#xD;
             study inclusion.&#xD;
&#xD;
          -  Patient shows evidence of severe infection other than pneumonia, or active internal&#xD;
             bleeding (characterized by recent decrease of blood hemoglobin concentration by more&#xD;
             than 2 g/dl).&#xD;
&#xD;
          -  Patient experiences new onset atrial fibrillation.&#xD;
&#xD;
          -  Patient has an elective surgery planned during the 30 days he/she is enrolled in the&#xD;
             study.&#xD;
&#xD;
          -  Patient has a psychiatric disease or a history of illicit drug use that would prohibit&#xD;
             him/her from complying with study requirements.&#xD;
&#xD;
          -  Prior exposure to VFI present.&#xD;
&#xD;
          -  History of any clinically significant allergic or negative reactions, side effects, or&#xD;
             anaphylaxis to fluorescent dyes, or dextran molecules present.&#xD;
&#xD;
          -  Patient requires intravenous vasodilators or inotropic agents (other than digoxin or&#xD;
             digitoxin) for heart failure.&#xD;
&#xD;
          -  Patient undergoes chronic dialysis (for example peritoneal or hemodialysis)&#xD;
             treatments.&#xD;
&#xD;
          -  Patient is in cardiogenic shock or on vasopressors.&#xD;
&#xD;
          -  Hypotension as defined by blood pressure ≤ 90 mm Hg systolic and/or ≤ 50 mm Hg&#xD;
             diastolic exists.&#xD;
&#xD;
          -  Patient has significant non-cardiac disease of other organ system (eg, malignancies,&#xD;
             significant neurological disease).&#xD;
&#xD;
          -  Patient does not have a working telephone.&#xD;
&#xD;
          -  Patient is pregnant or nursing (lactating), where pregnancy is defined as the state of&#xD;
             a female after conception and until the termination of gestation, confirmed by a&#xD;
             positive human chorionic gonadotropin (hCG) laboratory test.&#xD;
&#xD;
          -  Lack of willingness to storage and disclosure of pseudonymous disease data in the&#xD;
             context of the clinical trial present.&#xD;
&#xD;
          -  Patient has a participation in another interventional clinical trial during this study&#xD;
             or within 30 days (or longer) before entry into this study (as a minimum; 5 x&#xD;
             elimination half-life / terminal elimination of an investigational medicinal product).&#xD;
&#xD;
          -  Patient is legally detained in an official institution.&#xD;
&#xD;
          -  Patient is dependent on the sponsor, the investigator, or the trial sites.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kai M Schmidt-Ott, Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Charite University, Berlin, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Charité - Universitätsmedizin Berlin</name>
      <address>
        <city>Berlin</city>
        <zip>13353</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>January 8, 2019</study_first_submitted>
  <study_first_submitted_qc>January 15, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <results_first_submitted>July 28, 2021</results_first_submitted>
  <results_first_submitted_qc>October 20, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">November 17, 2021</results_first_posted>
  <last_update_submitted>October 20, 2021</last_update_submitted>
  <last_update_submitted_qc>October 20, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 17, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Charite University, Berlin, Germany</investigator_affiliation>
    <investigator_full_name>Kai Schmidt-Ott</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>congestive heart failure</keyword>
  <keyword>glomerular filtration rate</keyword>
  <keyword>plasma volume</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 11, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/48/NCT03808948/Prot_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 3, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/48/NCT03808948/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A totally of 50 hospitalized patients were enrolled between January 10th, 2019 and August 15th, 2019.</recruitment_details>
      <pre_assignment_details>No patients were excluded after enrollment but before assignment to the treatment group.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>All Patients</title>
          <description>VFI dose: 47 mg / 3 mL Number of doses: 2 Route of administration: intravenous&#xD;
VFI: The IV-administered visible fluorescent injectate (VFI)™ agent comprises a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>All Patients</title>
          <description>VFI dose: 47 mg / 3 mL Number of doses: 2 Route of administration: intravenous&#xD;
VFI: The IV-administered visible fluorescent injectate (VFI)™ agent comprises a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="50"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="72.5" spread="13.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="48"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Germany</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight day 1 (kg)</title>
          <units>kilograms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="89.21" spread="22.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height day 1 (cm)</title>
          <units>Centimeters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="172.84" spread="10.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI day 1 (kg/m2)</title>
          <units>Kilograms / meter squared</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29.7" spread="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Treatment Related AEs and Serious Adverse Events (SAEs)</title>
        <description>The percentage of treatment emergent SAEs considered to be surely related to the VFI should be zero.</description>
        <time_frame>30 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Patients</title>
            <description>VFI dose: 47 mg / 3 mL Number of doses: 2 Route of administration: intravenous&#xD;
VFI: The IV-administered visible fluorescent injectate (VFI)™ agent comprises a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Related AEs and Serious Adverse Events (SAEs)</title>
          <description>The percentage of treatment emergent SAEs considered to be surely related to the VFI should be zero.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage Difference in Mean Plasma Concentration of FD003 Over the 15-, 30-, and 60-minute Blood Draws on Days 1 and 3</title>
        <description>Function of the FAST PV measurement will be assessed by determining the plasma stability of the FD003 high molecular weight marker over the 15, 30, and 60 minute blood draws and applying the following criteria:&#xD;
The FAST PV measurement is considered as stable, if the mean plasma concentration of FD003 at 30 minutes is not more than 10% lower than the mean plasma concentration at 15 minutes AND if the mean plasma concentration at 60 minutes is not more than 10% lower than the mean plasma concentration at 30 minutes&#xD;
We will determine the percentage of patients which show a decline in the plasma concentration of FD003 of more than 10% from 15min to 30min and separately from 30 min to 60min. This percentage should be ideally close to 0.</description>
        <time_frame>3 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Patients</title>
            <description>VFI dose: 47 mg / 3 mL Number of doses: 2 Route of administration: intravenous&#xD;
VFI: The IV-administered visible fluorescent injectate (VFI)™ agent comprises a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Difference in Mean Plasma Concentration of FD003 Over the 15-, 30-, and 60-minute Blood Draws on Days 1 and 3</title>
          <description>Function of the FAST PV measurement will be assessed by determining the plasma stability of the FD003 high molecular weight marker over the 15, 30, and 60 minute blood draws and applying the following criteria:&#xD;
The FAST PV measurement is considered as stable, if the mean plasma concentration of FD003 at 30 minutes is not more than 10% lower than the mean plasma concentration at 15 minutes AND if the mean plasma concentration at 60 minutes is not more than 10% lower than the mean plasma concentration at 30 minutes&#xD;
We will determine the percentage of patients which show a decline in the plasma concentration of FD003 of more than 10% from 15min to 30min and separately from 30 min to 60min. This percentage should be ideally close to 0.</description>
          <units>Percent difference, plasma concentration</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Difference between Day 1 mean plasma concentration of FD003 at 15 minutes and 30 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.36" spread="7.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Difference between Day 3 mean plasma concentration of FD003 at 15 minutes and 30 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.12" spread="11.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>% difference between Day 1 mean plasma concentration of FD003 at 30 minutes and 60 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8" spread="5.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>% difference between Day 3 mean plasma concentration of FD003 at 30 minutes and 60 minutes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.79" spread="8.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Accuracy Between Estimated PV (ePV) on Days 1 and 3 (by Established Measures) and Measured PV (mPV; as Assessed by FAST Methodology) Defined as the Percentage of the Population With a &lt;15% and &lt;30% Difference Between ePV and mPV</title>
        <description>The percentage difference between ePV and mPV were evaluated to consider the percentage of the population with a &lt;15% and &lt;30% difference between ePV and mPV on day 1 and day 3</description>
        <time_frame>3 days</time_frame>
        <population>One patient did not have a hematocrit available for ePV determination, fourteen patients did not have day 3 measurements of mPV.</population>
        <group_list>
          <group group_id="O1">
            <title>All Patients</title>
            <description>VFI dose: 47 mg / 3 mL Number of doses: 2 Route of administration: intravenous&#xD;
VFI: The IV-administered visible fluorescent injectate (VFI)™ agent comprises a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.</description>
          </group>
        </group_list>
        <measure>
          <title>Accuracy Between Estimated PV (ePV) on Days 1 and 3 (by Established Measures) and Measured PV (mPV; as Assessed by FAST Methodology) Defined as the Percentage of the Population With a &lt;15% and &lt;30% Difference Between ePV and mPV</title>
          <description>The percentage difference between ePV and mPV were evaluated to consider the percentage of the population with a &lt;15% and &lt;30% difference between ePV and mPV on day 1 and day 3</description>
          <population>One patient did not have a hematocrit available for ePV determination, fourteen patients did not have day 3 measurements of mPV.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="49"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Number patients where ePV (Kaplan Hakim) was within 15% of mPV day1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number patients where ePV (Kaplan Hakim) was within 30% of mPV day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number patients where ePV (Kaplan Hakim) was within 15% of mPV day3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number patients where ePV (Kaplan Hakim) was within 30% of mPV day3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Accuracy Between Estimated Total Blood Volume (TBV) on Days 1 and 3 and Measured TBV (mTBV; Calculated From mPV and Measured Hematocrit) Defined as the Percentage of the Population With a &lt;15% and &lt;30% Difference Between ePV and mPV</title>
        <description>Accuracy between the Nadler's Formula as an estimate of total blood volume (TBV) and measured blood volume (mTBV) on days 1 and 3 as determined by the percentage of the population with a &lt;15% and &lt;30% difference between ePV and mPV</description>
        <time_frame>3 days</time_frame>
        <population>One patient did not have a hematocrit on day 1 for calculation of mTBV and eTBV, twelve patients did not receive a second measurement on day 3, two patients that recieved a second measurement, did not have a hematocrit on day 3 for calculation of mTBV and eTBV</population>
        <group_list>
          <group group_id="O1">
            <title>All Patients</title>
            <description>VFI dose: 47 mg / 3 mL Number of doses: 2 Route of administration: intravenous&#xD;
VFI: The IV-administered visible fluorescent injectate (VFI)™ agent comprises a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.</description>
          </group>
        </group_list>
        <measure>
          <title>Accuracy Between Estimated Total Blood Volume (TBV) on Days 1 and 3 and Measured TBV (mTBV; Calculated From mPV and Measured Hematocrit) Defined as the Percentage of the Population With a &lt;15% and &lt;30% Difference Between ePV and mPV</title>
          <description>Accuracy between the Nadler's Formula as an estimate of total blood volume (TBV) and measured blood volume (mTBV) on days 1 and 3 as determined by the percentage of the population with a &lt;15% and &lt;30% difference between ePV and mPV</description>
          <population>One patient did not have a hematocrit on day 1 for calculation of mTBV and eTBV, twelve patients did not receive a second measurement on day 3, two patients that recieved a second measurement, did not have a hematocrit on day 3 for calculation of mTBV and eTBV</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="49"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Number of patients where eTBV was within 15% of mTBV value day1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of patients where eTBV was within 30% of mTBV value day1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of patients where eTBV was within 15% of mTBV value day3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of patients where eTBV was within 30% of mTBV value day3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Accuracy of eGFR Determined by CKD-EPI-SCr and mGFR on Day 1 and Day 3 Defined the Percentage of the Population With a &lt;15% and &lt;30% Difference Between eGFR and mGFR</title>
        <description>To evaluate whether estimated Glomerular Filtration Rate (eGFR) (calculation by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula) on days 1 and 3 provides an accurate estimate of measured GFR (mGFR; assessed by FAST methodology) in heart failure patients under-going active fluid management, determined by the percentage of patients with a &lt;15% and &lt;30% difference between eGFR and mGFR</description>
        <time_frame>3 days</time_frame>
        <population>twelve patients did not have mGFR measurement on day 3, so only 38 patients are analyzed on day 3</population>
        <group_list>
          <group group_id="O1">
            <title>All Patients</title>
            <description>VFI dose: 47 mg / 3 mL Number of doses: 2 Route of administration: intravenous&#xD;
VFI: The IV-administered visible fluorescent injectate (VFI)™ agent comprises a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.</description>
          </group>
        </group_list>
        <measure>
          <title>Accuracy of eGFR Determined by CKD-EPI-SCr and mGFR on Day 1 and Day 3 Defined the Percentage of the Population With a &lt;15% and &lt;30% Difference Between eGFR and mGFR</title>
          <description>To evaluate whether estimated Glomerular Filtration Rate (eGFR) (calculation by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula) on days 1 and 3 provides an accurate estimate of measured GFR (mGFR; assessed by FAST methodology) in heart failure patients under-going active fluid management, determined by the percentage of patients with a &lt;15% and &lt;30% difference between eGFR and mGFR</description>
          <population>twelve patients did not have mGFR measurement on day 3, so only 38 patients are analyzed on day 3</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Number of patients where eGFR was within 15% of mGFR value on Day 1.</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of patients where eGFR was within 15% of mGFR value on Day 3.</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of patients where eGFR was within 30% of mGFR value on Day 1.</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of patients where eGFR was within 30% of mGFR value on Day 3.</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of the Population That Developed Acute Kidney Injury (AKI) Within the Following 48-72 Hour and Prediction of AKI by mGFR/eGFR Ratio on Days 1 and 3</title>
        <description>To evaluate the percentage of patients developing acute kidney injury (AKI) within the following 48-72 hours on day 1 and day 3 and to evaluate whether patients with a low mGFR/eGFR ratio on days 1 and 3 are at higher risk of developing acute kidney injury (AKI) within the following 48-72 hours using a binary logisitic regression with AKI as binary outcome and mGFR/eGFR as independent variate</description>
        <time_frame>48-72h</time_frame>
        <population>36 patients had data for AKI determination 48h after day 1, 32 patients had data for AKI determination after day 3</population>
        <group_list>
          <group group_id="O1">
            <title>All Patients</title>
            <description>VFI dose: 47 mg / 3 mL Number of doses: 2 Route of administration: intravenous&#xD;
VFI: The IV-administered visible fluorescent injectate (VFI)™ agent comprises a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of the Population That Developed Acute Kidney Injury (AKI) Within the Following 48-72 Hour and Prediction of AKI by mGFR/eGFR Ratio on Days 1 and 3</title>
          <description>To evaluate the percentage of patients developing acute kidney injury (AKI) within the following 48-72 hours on day 1 and day 3 and to evaluate whether patients with a low mGFR/eGFR ratio on days 1 and 3 are at higher risk of developing acute kidney injury (AKI) within the following 48-72 hours using a binary logisitic regression with AKI as binary outcome and mGFR/eGFR as independent variate</description>
          <population>36 patients had data for AKI determination 48h after day 1, 32 patients had data for AKI determination after day 3</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Number of patients with AKI within 48h after day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="36"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of patients with AKI within 48h after day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="32"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Binary logistic regression with mGFR/eGFR ratio as independent variate, AKI as binary outcome</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.4842</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.62</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.08</ci_lower_limit>
            <ci_upper_limit>1.97</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients Who Are Refractory to Diuretic Therapy</title>
        <description>Being refractory to diuretic therapy (defined as any dosage increases of furosemide i.v. dose equivalent, adding thiazide after day 1, requirement of ultrafiltration/RRT within the next 24-48 hours, failure to improve subjectively in PGA and dyspnoea scales, failure of mean weight loss during the study period Day 1-Day 5 of at least 0,5 kg/d).</description>
        <time_frame>5 days</time_frame>
        <population>one patient did not have weight data, two patients were discharged after first measurement (day 1) so no lineary observation was possible</population>
        <group_list>
          <group group_id="O1">
            <title>All Patients</title>
            <description>VFI dose: 47 mg / 3 mL Number of doses: 2 Route of administration: intravenous&#xD;
VFI: The IV-administered visible fluorescent injectate (VFI)™ agent comprises a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients Who Are Refractory to Diuretic Therapy</title>
          <description>Being refractory to diuretic therapy (defined as any dosage increases of furosemide i.v. dose equivalent, adding thiazide after day 1, requirement of ultrafiltration/RRT within the next 24-48 hours, failure to improve subjectively in PGA and dyspnoea scales, failure of mean weight loss during the study period Day 1-Day 5 of at least 0,5 kg/d).</description>
          <population>one patient did not have weight data, two patients were discharged after first measurement (day 1) so no lineary observation was possible</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Not refractory to diuretics</title>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Refractory to diuretics</title>
                  <measurement_list>
                    <measurement group_id="O1" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Population in Which Clinical Decision Making Would Have Been Influenced by Adding FAST GFR and PV Measurements to Clinical Routine Determined by Survey Response (by an Adjudication Committee)</title>
        <description>Percentage of patients for whom the data decision committee decided to increase or decrease the dose of diuretics, guideline-directed medical therapy (GDMT), beta-blockers, or RAAS inhibitors from the dose indicated by the treating physician after considering the mPV/mTBV determined using FAST BioMedical technology.</description>
        <time_frame>3 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>All Patients</title>
            <description>VFI dose: 47 mg / 3 mL Number of doses: 2 Route of administration: intravenous&#xD;
VFI: The IV-administered visible fluorescent injectate (VFI)™ agent comprises a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Population in Which Clinical Decision Making Would Have Been Influenced by Adding FAST GFR and PV Measurements to Clinical Routine Determined by Survey Response (by an Adjudication Committee)</title>
          <description>Percentage of patients for whom the data decision committee decided to increase or decrease the dose of diuretics, guideline-directed medical therapy (GDMT), beta-blockers, or RAAS inhibitors from the dose indicated by the treating physician after considering the mPV/mTBV determined using FAST BioMedical technology.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Number or patients where adjudication committee would have changed diuretic dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number or patients where adjudication committee would have changed RAASi dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number or patients where adjudication committee would have changed beta blocker dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number or patients where adjudication committee would have changed GDMT</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>30 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>All Patients</title>
          <description>VFI dose: 47 mg / 3 mL Number of doses: 2 Route of administration: intravenous&#xD;
VFI: The IV-administered visible fluorescent injectate (VFI)™ agent comprises a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (Unspecified)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombosis mesenteric vessel</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Multiple organ dysfunction syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Endocarditis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Infectious pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Anaemia postoperative</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Lumbar vertebral fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Post procedural fistula</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Postoperative delirium</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Troponin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Fluid overload</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney Injury</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Azotaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertensive crisis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (Unspecified)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="37" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Splenomegaly</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Arrhythmia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Phimosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Abdominal pain lower</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Duodenal ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Erosive oesophagitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Gastrointestinal angiodysplasia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Intestinal polyp</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Large intestine polyp</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Melaena</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Subileus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Thrombosis mesenteric vessel</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Varices oesophageal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Multiple organ dysfunction syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Xerosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Drug hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Endocarditis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Gastroenteritis rotavirus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Infectious pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Oesophageal candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Anaemia postoperative</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Lumbar vertebral fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Post procedural fever</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Post procedural fistula</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Post procedural haematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Postoperative delirium</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Wound</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Troponin increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Bilirubin conjugated increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>C-reactive protein increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Blood creatine phosphokinase abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Brain natriuretic peptide increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Procalcitonin abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Procalcitonin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Electrolyte imbalance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Fluid overload</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Hypernatraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Hyperphosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Hypoproteinaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Iron deficiency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Metabolic acidosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Vitamin D deficiency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Joint swelling</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Colon adenoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Lung neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Cerebral infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Dementia Alzheimer's type</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Partial seizures</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Sleep disorder</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Depressed mood</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Disorientation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Azotaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>End stage renal disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Urinary tract obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Benign prostatic hyperplasia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Penile haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Diaphragmatic disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Painful respiration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Skin disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Social circumstances</title>
            <event_list>
              <event>
                <sub_title>Immobile</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Coronary arterial stent insertion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Hypertensive crisis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Thrombophlebitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Prof. Dr. med. Kai Schmidt-Ott</name_or_title>
      <organization>Charité - Universitätsmedizin Berlin</organization>
      <phone>+4930450614671</phone>
      <email>Kai.schmidt-ott@charite.de</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03808948
org study id: EmPaKt-CHF
secondary id: 2018-002638-18
nct id: NCT03808948
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
This is an investigator-initiated, one-armed, phase 2 clinical trial using an injectable
      fluorescent tracer to assay and evaluate measured plasma volume (mPV) and measured glomerular
      filtration rate (mGFR) in hospitalized patients with acute decompensated congestive heart
      failure (CHF).
This investigator-initiated, one-armed study is designed to evaluate the safety and function
      of the FAST PV and mGFR Technology in patients with CHF. Data from the FAST PV and mGFR
      Technology will not be evaluable by the treating physician, but will be made available to the
      study investigators and to an adjudication committee.

      Patients enrolled in the study will be administered the VFI (Day 1) and with a second dose
      occurring 24-48 hours after the initial dose (Day 3).

      After consenting to be enrolled in the study, patients meeting the enrollment criteria will
      receive a single dose of two component VFI. Blood draws (3 mL) will be collected pre-dose and
      at 15, 30, 60, and 180 minutes post-dose, which will be subsequently used to determine the
      patient's blood volume and mGFR using the FAST PV and mGFR Technology. Patients will be
      treated according to standard of care throughout the time of their hospitalization. A second
      dose of VFI will be administered 48 (+/- 5) hours after the initial dosing. Again, blood
      draws (3 mL) will be collected pre-dose and at 15, 30, 60, and 180 minutes post-dose. Plasma
      volume (PV) was determined using the average concentrations of the higher molecular marker of
      VFI of the early 15 min and the 60 min time point. The concentration of the small dextran GFR
      marker at time zero was back calculated from the measured PV by dividing the known dose into
      the measured PV. The time points were then fitted using atwo-compartment model and the
      resulting area under the curve was calculated. The use of the time point 0 determination
      helped to better resolve the shape of the clearance curve.

      Study-related blood samples will be obtained on days 1, 2, 3, 4, and 5 to measure serum
      creatinine (days 1-5), hematocrit (days 1, 3), and N-terminal pro-brain natriuretic peptide
      (NT-pro-BNP), creatine phosphokinase (CPK), alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), alkaline phosphatase, bilirubin total and direct, and international
      normalized ratio (INR) (days 1, 3, and 5); and will be stored for future testing of
      additional parameters in the research fields of acute decompensated heart failure and acute
      kidney injury.

      The available laboratory values will be entered in the Dosing Day Case Report Form (CRF),
      along with any copies of physician's notes and orders entered that day. Prior to
      administering the first and second dose of VFI, the physician will be asked to complete a
      very brief survey to provide a qualitative assessment of the patient's perceived volume
      status and renal function prior to initiating the FAST PV and mGFR measurements.

      Laboratory values and assessments will be captured on each day that the VFI is administered,
      and these data will be entered into the CRF. Any adverse events (AEs) determined by the
      investigator to be related or possibly related to the VFI will be captured. Patients will
      receive a followup phone call 7 days (± 2 days) after the first dose of VFI was administered,
      and a second follow up call 30 days after the first dose of VFI was administered as an end of
      study (EOS) follow up call. Any AEs determined by the investigator will be captured during
      the follow up calls and will be followed to resolution. Additionally, in-person follow-up
      visits may be scheduled as needed.

      Upon conclusion of the study, the recorded clinical data will be provided to an independent
      data adjudication committee (DAC) in a pseudonymized fashion. The DAC will be asked to review
      the available data at the time of the first dosing, and the measured GFR and PV data for the
      first dosing day will be provided. The DAC will then be asked to fill out a survey asking
      whether the mGFR and PV data would have influenced their treatment decision, and if so,
      indicate what they would have done differently.

      Following the evaluation of mGFR and PV data at the time of the initial VFI dose, the mGFR
      and PV data determined from the second VFI dosing point will be provided to the DAC. The DAC
      will then be asked to fill out a separate survey asking how the actual measured PV and GFR
      differ from the clinical assessments, whether the mGFR and PV data would influence their
      treatment decision, and if so, indicate what they would have done differently.

      After all assessments have been completed, the DAC will review the results of their analyses
      and compile a summary report on the secondary endpoints as well as their assessment of the
      overall impact of the PV and mGFR on clinical decision making.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Number of Participants With Treatment Related AEs and Serious Adverse Events (SAEs)
time frame: 30 days
description: The percentage of treatment emergent SAEs considered to be surely related to the VFI should be zero.
measure: Percentage Difference in Mean Plasma Concentration of FD003 Over the 15-, 30-, and 60-minute Blood Draws on Days 1 and 3
time frame: 3 days
description: Function of the FAST PV measurement will be assessed by determining the plasma stability of the FD003 high molecular weight marker over the 15, 30, and 60 minute blood draws and applying the following criteria:
The FAST PV measurement is considered as stable, if the mean plasma concentration of FD003 at 30 minutes is not more than 10% lower than the mean plasma concentration at 15 minutes AND if the mean plasma concentration at 60 minutes is not more than 10% lower than the mean plasma concentration at 30 minutes
We will determine the percentage of patients which show a decline in the plasma concentration of FD003 of more than 10% from 15min to 30min and separately from 30 min to 60min. This percentage should be ideally close to 0.
measure: Accuracy Between Estimated PV (ePV) on Days 1 and 3 (by Established Measures) and Measured PV (mPV; as Assessed by FAST Methodology) Defined as the Percentage of the Population With a <15% and <30% Difference Between ePV and mPV
time frame: 3 days
description: The percentage difference between ePV and mPV were evaluated to consider the percentage of the population with a <15% and <30% difference between ePV and mPV on day 1 and day 3
measure: Accuracy Between Estimated Total Blood Volume (TBV) on Days 1 and 3 and Measured TBV (mTBV; Calculated From mPV and Measured Hematocrit) Defined as the Percentage of the Population With a <15% and <30% Difference Between ePV and mPV
time frame: 3 days
description: Accuracy between the Nadler's Formula as an estimate of total blood volume (TBV) and measured blood volume (mTBV) on days 1 and 3 as determined by the percentage of the population with a <15% and <30% difference between ePV and mPV
measure: Accuracy of eGFR Determined by CKD-EPI-SCr and mGFR on Day 1 and Day 3 Defined the Percentage of the Population With a <15% and <30% Difference Between eGFR and mGFR
time frame: 3 days
description: To evaluate whether estimated Glomerular Filtration Rate (eGFR) (calculation by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula) on days 1 and 3 provides an accurate estimate of measured GFR (mGFR; assessed by FAST methodology) in heart failure patients under-going active fluid management, determined by the percentage of patients with a <15% and <30% difference between eGFR and mGFR
measure: Percentage of the Population That Developed Acute Kidney Injury (AKI) Within the Following 48-72 Hour and Prediction of AKI by mGFR/eGFR Ratio on Days 1 and 3
time frame: 48-72h
description: To evaluate the percentage of patients developing acute kidney injury (AKI) within the following 48-72 hours on day 1 and day 3 and to evaluate whether patients with a low mGFR/eGFR ratio on days 1 and 3 are at higher risk of developing acute kidney injury (AKI) within the following 48-72 hours using a binary logisitic regression with AKI as binary outcome and mGFR/eGFR as independent variate
measure: Percentage of Patients Who Are Refractory to Diuretic Therapy
time frame: 5 days
description: Being refractory to diuretic therapy (defined as any dosage increases of furosemide i.v. dose equivalent, adding thiazide after day 1, requirement of ultrafiltration/RRT within the next 24-48 hours, failure to improve subjectively in PGA and dyspnoea scales, failure of mean weight loss during the study period Day 1-Day 5 of at least 0,5 kg/d).
measure: Percentage of Population in Which Clinical Decision Making Would Have Been Influenced by Adding FAST GFR and PV Measurements to Clinical Routine Determined by Survey Response (by an Adjudication Committee)
time frame: 3 days
description: Percentage of patients for whom the data decision committee decided to increase or decrease the dose of diuretics, guideline-directed medical therapy (GDMT), beta-blockers, or RAAS inhibitors from the dose indicated by the treating physician after considering the mPV/mTBV determined using FAST BioMedical technology.
arm group label: All Patients
arm group type: Experimental
description: VFI dose: 47 mg / 3 mL Number of doses: 2 Route of administration: intravenous
intervention type: Device
intervention name: VFI
description: The IV-administered visible fluorescent injectate (VFI)™ agent comprises a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
arm group label: All Patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kai M Schmidt-Ott, Dr. med.
role: Principal Investigator
affiliation: Charite University, Berlin, Germany
facility: 
country: Germany
responsible party type: Principal Investigator
investigator affiliation: Charite University, Berlin, Germany
investigator full name: Kai Schmidt-Ott
investigator title: Principal Investigator
mesh term: Heart Failure
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 