xml: <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/NCT05975021</url>
    </required_header>
    <id_info>
      <org_study_id>04-CL-2201</org_study_id>
      <secondary_id>CT Id: 2023-507243-11-00</secondary_id>
      <nct_id>NCT05975021</nct_id>
    </id_info>
    <brief_title>A Safety and Efficacy Trial of Istaroxime for Cardiogenic Shock Stage C</brief_title>
    <acronym>SEISMiC-C</acronym>
    <official_title>A Multicenter, Randomized, Placebo-Controlled, Parallel Group Trial on the Safety and Efficacy of Istaroxime for Cardiogenic Shock SCAI Stage C</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Windtree Therapeutics</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Windtree Therapeutics</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The current trial aims to assess the effect of istaroxime in patients with SCAI Stage C&#xD;
        Cardiogenic Shock (CS). These patients look unwell, frequently with a sudden change in mental&#xD;
        status, mottled and cool extremities, and delayed capillary refill, as well as signs of&#xD;
        congestion and relative low blood pressure and signs of hypoperfusion (reduced oxygen to&#xD;
        organs) which frequently require support with rescue therapies including inotropes,&#xD;
        vasopressors, or mechanical devices.&#xD;
  &#xD;
        Windtree Therapeutics, Inc. has been studying istaroxime, which has the potential to treat&#xD;
        patients in this condition without some of the disadvantages of existing therapies being used&#xD;
        to treat patients with acute heart failure and CS.&#xD;
  &#xD;
        Participants enrolled in this trial will receive standard of care (SoC) therapy for heart&#xD;
        failure and CS. Additionally, half of the participants will be randomly chosen to receive&#xD;
        istaroxime. Istaroxime has the potential to increase blood pressure and improve cardiac&#xD;
        function.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 1, 2023</start_date>
    <completion_date type="Anticipated">July 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">July 1, 2024</primary_completion_date>
    <phase>Phase 1/Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>This is a pilot, multinational, multicenter, randomized, double-blind, placebo-controlled, safety and efficacy trial. Participants will consist of males or females 18 to 85 years of age hospitalized for acute decompensated heart failure (ADHF) with persistent hypotension (systolic blood pressure [SBP] 70 to 90 mmHg for two readings with concomitant signs of hypoperfusion), and mild to moderate renal impairment.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Care Provider, Investigator)</masking>
      <masking_description>Trial treatment will be blinded to the trial staff. Istaroxime and placebo are both lyophilized powders and are put into identical vials. Each trial box will be numbered with a unique identifier, which will not allow the trial staff to ascertain which treatment is being used.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>SBP AUC 0-6</measure>
      <time_frame>Start of infusion to 6 hours</time_frame>
      <description>Systolic blood pressure (SBP) area under the curve (AUC) from start of infusion to 6 hours</description>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Cardiogenic Shock</condition>
    <arm_group>
      <arm_group_label>Istaroxime</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Istaroxime delivered as an IV infusion via a syringe pump. Dosage regime is 1.0 µg/kg/min for 6 hours, 1.0 or 0.5 µg/kg/min for 18 hours, 0.5 µg/kg/min for 24 hours. Total duration 48 hours.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Placebo (lactose) delivered as an IV infusion via a syringe pump. Total duration 48 hours.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Istaroxime</intervention_name>
      <description>IV infusion via a syringe pump. Dosage of 1.0 µg/kg/min for 6 hours; 1.0 or 0.5 µg/kg/min for 18 hours, 0.5 µg/kg/min for 24 hours. Total duration 48 hours.</description>
      <arm_group_label>Istaroxime</arm_group_label>
      <other_name>PST2744</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>IV infusion via a syringe pump. Total duration 48 hours.</description>
      <arm_group_label>Placebo</arm_group_label>
      <other_name>Lactate</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Signed informed consent form (ICF);&#xD;
  &#xD;
            -  Clinical presentation consistent with SCAI Stage C cardiogenic shock caused by ADHF&#xD;
               and meeting the criteria in below table;&#xD;
  &#xD;
            -  Admitted to ICU within 36 hours prior to randomization with congestion on chest x-ray&#xD;
               or lung ultrasound and BNP ≥ 400 pg/mL or NT-proBNP ≥ 1400 pg/mL;&#xD;
  &#xD;
            -  Males and females, 18 to 85 years of age (inclusive);&#xD;
  &#xD;
            -  History of left ventricular ejection fraction (LVEF) ≤ 40%;&#xD;
  &#xD;
            -  Persistent hypotension defined as SBP between 70 and 90 mmHg for 2 readings with&#xD;
               concomitant signs of hypoperfusion;&#xD;
  &#xD;
            -  Echocardiogram during initial hospitalization confirming ejection fraction ≤ 40% and&#xD;
               no evidence of other pathology to confound interpretation of cardiac physiology (eg,&#xD;
               pericardial effusion).&#xD;
  &#xD;
          Table: Definition of SCAI Stage C Required for Inclusion. These criteria must be present at&#xD;
          screening or prior to screening in patients actively treated by vasoactive agents or/and&#xD;
          inotropes concomitantly (at the same time)&#xD;
  &#xD;
          Must have at Least One of:&#xD;
  &#xD;
            -  Hypoperfusion: Venous Lactate ≥ 2 mmol/L, urine output &lt; 30 mL/hour, cold and clammy&#xD;
               or acute alteration in mental status.&#xD;
  &#xD;
            -  Hemodynamic Instability: SBP 70-90 mmHg, cardiac index &lt; 2.2 L/min/meter2 and PCW &gt; 15&#xD;
               mmHg&#xD;
  &#xD;
          Without Any Of:&#xD;
  &#xD;
            -  Venous lactate &gt; 5 mmol/L&#xD;
  &#xD;
            -  Worsening clinical status despite initial therapy (e.g., worsening hemodynamics,&#xD;
               worsening renal or liver function)&#xD;
  &#xD;
            -  ALT &gt;500 U/L (8.333 µkat/L)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patient is in SCAI B (BP increased above 90 mmHg despite no vasoactive or inotrope&#xD;
               therapy) or SCAI D (continuously deteriorating BP and hypoperfusion despite vasoactive&#xD;
               or inotrope therapy);&#xD;
  &#xD;
            -  Lactate &lt; 2 mmol/L (unless the patient meets the criteria in bullet 2 of Table 5-1) or&#xD;
               lactate &gt; 5 mmol/L prior to randomization;&#xD;
  &#xD;
            -  Cardiogenic shock due to any other condition besides acute decompensation of chronic&#xD;
               heart failure;&#xD;
  &#xD;
            -  Any of the following in the past 30 days: acute coronary syndrome, coronary&#xD;
               revascularization, MI, CABG, or percutaneous coronary intervention;&#xD;
  &#xD;
            -  Current (within 6 hours of screening) or anticipated need for treatment with renal&#xD;
               support including ultrafiltration, or mechanical circulatory, ventilatory or renal&#xD;
               support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation,&#xD;
               or any ventricular assist device) such as persistent hypoperfusion and hypotension;&#xD;
  &#xD;
            -  History of heart transplant or UNOS priority 1a heart transplant listing&#xD;
  &#xD;
            -  Ongoing treatment with digoxin (if digoxin was stopped before signing the ICF and the&#xD;
               digoxin plasma level is &lt; 0.5 ng/ml, the patient may be enrolled);&#xD;
  &#xD;
            -  Severe renal impairment (eGFR &lt; 30 ml/min, calculated by the MDRD formula);&#xD;
  &#xD;
            -  Hypersensitivity to the trial medication and its excipients (including known lactose&#xD;
               hypersensitivity) or any related medication;&#xD;
  &#xD;
            -  Stroke or TIA within 3 months;&#xD;
  &#xD;
            -  Severe obstructive valvular lesions including severe aortic or mitral stenosis;&#xD;
  &#xD;
            -  Primary hypertrophic or restrictive cardiomyopathy or systemic illness known to be&#xD;
               associated with infiltrative heart disease;&#xD;
  &#xD;
            -  Admission for AHF triggered primarily by a correctable etiology such as significant&#xD;
               arrhythmia (inclusive of atrial fibrillation as the main reason for admission),&#xD;
               infection, severe anemia, acute coronary syndrome, pulmonary embolism, exacerbation of&#xD;
               COPD, planned admission for device implantation, or over-diuresis as a cause of&#xD;
               hypotension;&#xD;
  &#xD;
            -  Pericardial constriction or active pericarditis;&#xD;
  &#xD;
            -  Significant ventricular arrhythmia prior to screening (such as sustained ventricular&#xD;
               tachycardia or ventricular fibrillation) or implantable cardioverter defibrillator&#xD;
               (ICD) shock within the past month or history of sudden death within 6 months;&#xD;
  &#xD;
            -  Cardiac resynchronization therapy (CRT), ICD, or pacemaker implantation within the&#xD;
               past month;&#xD;
  &#xD;
            -  Uncontrolled arrythmia;&#xD;
  &#xD;
            -  Sustained hypotension (SBP &lt; 70 mmHg) for at least 30 minutes from the time of arrival&#xD;
               to the hospital;&#xD;
  &#xD;
            -  Systolic BP &gt; 120 mmHg during the hour prior to randomization&#xD;
  &#xD;
            -  Cor pulmonale or other causes of isolated right-sided HF or not related to left&#xD;
               ventricular dysfunction;&#xD;
  &#xD;
            -  Acute respiratory distress syndrome;&#xD;
  &#xD;
            -  Suspected sepsis; fever &gt; 38° or active infection requiring IV antimicrobial&#xD;
               treatment;&#xD;
  &#xD;
            -  Body weight &lt; 40 kg or ≥ 150 kg;&#xD;
  &#xD;
            -  Laboratory exclusions:&#xD;
  &#xD;
                 1. Hemoglobin &lt; 9 g/dl,&#xD;
  &#xD;
                 2. Platelet count &lt; 100,000/µl,&#xD;
  &#xD;
                 3. Serum potassium &gt; 5.3 mmol/l or &lt; 3.5 mmol/l;&#xD;
  &#xD;
            -  A life expectancy &lt; 3 months based on the judgment of the investigator;&#xD;
  &#xD;
            -  Severe pulmonary or thyroid disease;&#xD;
  &#xD;
            -  Pregnant, planning on becoming pregnant, or currently breast-feeding;&#xD;
  &#xD;
            -  Ongoing drug or alcohol abuse;&#xD;
  &#xD;
            -  Participation in another interventional trial within the past 30 days.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>85 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Steven G Simonson, MD</last_name>
      <role>Study Director</role>
      <affiliation>Windtree Therapeutics, Inc.</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Phillip D Simmons, MS</last_name>
      <phone>215-488-9477</phone>
      <email>psimmons@windtreetx.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 26, 2023</study_first_submitted>
    <study_first_submitted_qc>July 26, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 3, 2023</study_first_posted>
    <last_update_submitted>August 3, 2023</last_update_submitted>
    <last_update_submitted_qc>August 3, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Shock, Cardiogenic</mesh_term>
      <mesh_term>Shock</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>The preparation and submittal for publication of a manuscript containing the study results shall be in accordance with a process determined by a mutual written agreement between Windtree and participating institutions.&#xD;
  The publication or presentation of any study results shall comply with all applicable privacy laws, including but not limited to HIPAA. This trial will be registered in the ClinicalTrials.gov and the CTIS databases, and results information from this trial will be submitted to both. In addition, every attempt will be made to publish results in peer-reviewed journals.</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_access_criteria>Mutual written agreement.</ipd_access_criteria>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05975021
  org study id: 04-CL-2201
  secondary id: CT Id: 2023-507243-11-00
  nct id: NCT05975021
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  The current trial aims to assess the effect of istaroxime in patients with SCAI Stage C
        Cardiogenic Shock (CS). These patients look unwell, frequently with a sudden change in mental
        status, mottled and cool extremities, and delayed capillary refill, as well as signs of
        congestion and relative low blood pressure and signs of hypoperfusion (reduced oxygen to
        organs) which frequently require support with rescue therapies including inotropes,
        vasopressors, or mechanical devices.
  
        Windtree Therapeutics, Inc. has been studying istaroxime, which has the potential to treat
        patients in this condition without some of the disadvantages of existing therapies being used
        to treat patients with acute heart failure and CS.
  
        Participants enrolled in this trial will receive standard of care (SoC) therapy for heart
        failure and CS. Additionally, half of the participants will be randomly chosen to receive
        istaroxime. Istaroxime has the potential to increase blood pressure and improve cardiac
        function.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: This is a pilot, multinational, multicenter, randomized, double-blind, placebo-controlled, safety and efficacy trial. Participants will consist of males or females 18 to 85 years of age hospitalized for acute decompensated heart failure (ADHF) with persistent hypotension (systolic blood pressure [SBP] 70 to 90 mmHg for two readings with concomitant signs of hypoperfusion), and mild to moderate renal impairment.
  primary purpose: Treatment
  masking: Triple (Participant, Care Provider, Investigator)
  masking description: Trial treatment will be blinded to the trial staff. Istaroxime and placebo are both lyophilized powders and are put into identical vials. Each trial box will be numbered with a unique identifier, which will not allow the trial staff to ascertain which treatment is being used.
  measure: SBP AUC 0-6
  time frame: Start of infusion to 6 hours
  description: Systolic blood pressure (SBP) area under the curve (AUC) from start of infusion to 6 hours
  arm group label: Istaroxime
  arm group type: Experimental
  description: Istaroxime delivered as an IV infusion via a syringe pump. Dosage regime is 1.0 µg/kg/min for 6 hours, 1.0 or 0.5 µg/kg/min for 18 hours, 0.5 µg/kg/min for 24 hours. Total duration 48 hours.
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Placebo (lactose) delivered as an IV infusion via a syringe pump. Total duration 48 hours.
  intervention type: Drug
  intervention name: Istaroxime
  description: IV infusion via a syringe pump. Dosage of 1.0 µg/kg/min for 6 hours; 1.0 or 0.5 µg/kg/min for 18 hours, 0.5 µg/kg/min for 24 hours. Total duration 48 hours.
  arm group label: Istaroxime
  other name: PST2744
  intervention type: Drug
  intervention name: Placebo
  description: IV infusion via a syringe pump. Total duration 48 hours.
  arm group label: Placebo
  other name: Lactate
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 85 Years
  healthy volunteers: No
  last name: Steven G Simonson, MD
  role: Study Director
  affiliation: Windtree Therapeutics, Inc.
  last name: Phillip D Simmons, MS
  phone: 215-488-9477
  email: psimmons@windtreetx.com
  responsible party type: Sponsor
  mesh term: Shock, Cardiogenic
  mesh term: Shock
  sharing ipd: Yes
  ipd description: The preparation and submittal for publication of a manuscript containing the study results shall be in accordance with a process determined by a mutual written agreement between Windtree and participating institutions.
  The publication or presentation of any study results shall comply with all applicable privacy laws, including but not limited to HIPAA. This trial will be registered in the ClinicalTrials.gov and the CTIS databases, and results information from this trial will be submitted to both. In addition, every attempt will be made to publish results in peer-reviewed journals.
  ipd info type: Study Protocol
  ipd info type: Informed Consent Form (ICF)
  ipd info type: Clinical Study Report (CSR)
  ipd access criteria: Mutual written agreement.