<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/NCT03763929</url>
  </required_header>
  <id_info>
    <org_study_id>100-501</org_study_id>
    <nct_id>NCT03763929</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Trans Sodium Crocetinate (TSC) for Treatment of Suspected Stroke</brief_title>
  <acronym>PHAST-TSC</acronym>
  <official_title>Double-Blind, Randomized, Placebo-Controlled, Phase 2 Study of Efficacy and Safety of Trans Sodium Crocetinate (TSC) Administered Onboard Emergency Vehicles for Treatment of Suspected Stroke: PHAST-TSC</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Diffusion Pharmaceuticals Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Virginia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Diffusion Pharmaceuticals Inc</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>
      This study will assess the potential efficacy and safety of TSC as early treatment for both&#xD;
      ischemic and hemorrhagic stroke when administered while subject is in ambulance being&#xD;
      transported to hospital.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter, randomized, placebo-controlled, double-blind, parallel group trial of&#xD;
      intravenous trans sodium crocetinate (TSC) initiated by emergency medical service (EMS)&#xD;
      responders in the field within 2 hours of symptom onset in 160 subjects with acute stroke.&#xD;
      The primary objectives of the study are to evaluate the efficacy and safety of&#xD;
      field-initiated TSC in improving the long-term functional outcome of subjects with acute&#xD;
      stroke.&#xD;
&#xD;
      Subjects with acute stroke will be identified and screened in the ambulance by (EMS)&#xD;
      responders who have received training in basic and advanced cardiac life support, stroke&#xD;
      recognition, and specific procedures relevant to the proposed study. The EMS responders will&#xD;
      contact a Study Neurologist, who will enroll eligible stroke patients into the study. Effort&#xD;
      will be made to obtain prospective informed consent in the ambulance when deemed to be&#xD;
      feasible. If not feasible, subjects will be enrolled under regulations for exception from&#xD;
      explicit informed consent (EFIC) in emergency research circumstances, after public disclosure&#xD;
      and community consultation. Written informed consent to continue in the study is obtained&#xD;
      from subjects or their legally authorized representatives as soon as possible after hospital&#xD;
      arrival.&#xD;
&#xD;
      EMS responders will deliver the single, field, bolus dose of study agent, TSC at 0.25 mg/kg&#xD;
      or matched placebo, followed after hospital arrival by standard of care (SOC). No additional&#xD;
      study drug will be administered in the hospital. Follow-up assessments will be performed at&#xD;
      Emergency Department (ED) arrival, 24 hours, 48 hours, Day 4, Day 30, and Day 90. The study&#xD;
      will be performed at up to 30 receiving hospital sites in Los Angeles County, CA, and central&#xD;
      Virginia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The study was stopped due to lack of meaningful enrollment due to the COVID-19 pandemic.&#xD;
  </why_stopped>
  <start_date type="Actual">August 22, 2019</start_date>
  <completion_date type="Actual">October 19, 2020</completion_date>
  <primary_completion_date type="Actual">October 19, 2020</primary_completion_date>
  <phase>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>Multicenter, randomized, placebo-controlled, double-blind, parallel group</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>TSC injections will be prepared and injected by unblinded personnel on each ambulance. All other study personnel will be blinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Global Disability Level on the Modified Rankin Score (mRS)</measure>
    <time_frame>90 days</time_frame>
    <description>Modified Rankin Scale (mRS) is a measure of global disability. Total scale range is 0-6, with lower values indicating better outcomes.&#xD;
0 = No symptoms at all&#xD;
= No significant disability despite symptoms; able to carry out all usual duties and activities&#xD;
= Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance&#xD;
= Moderate disability; requiring some help, but able to walk without assistance&#xD;
= Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance&#xD;
= Severe disability; bedridden, incontinent and requiring constant nursing care and attention&#xD;
= Dead</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Stroke, Acute</condition>
  <arm_group>
    <arm_group_label>Trans Sodium Crocetinate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Trans sodium crocetinate (TSC) will be administered intravenously as a bolus to subjects randomized to experimental drug. The bolus dose will consist of 0.25 mg/kg of TSC based on the estimated subject weight.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The placebo consists of commercially available sterile saline. Placebo will be administered intravenously as a bolus to subjects randomized to placebo. The volume of sterile saline will be based on the estimated subject weight.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trans-Sodium Crocetinate</intervention_name>
    <description>In the study drug kit containing the experimental drug (TSC), TSC will be reconstituted with the Sterile Water for Injection (USP) supplied in the same kit. There will be an unblinded paramedic who will reconstitute and inject the TSC on the ambulance.</description>
    <arm_group_label>Trans Sodium Crocetinate</arm_group_label>
    <other_name>TSC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The study drug kit containing placebo (sterile saline for Injection) will be prepared and injected by the unblinded paramedic on the ambulance.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 40-85, inclusive&#xD;
&#xD;
          2. Last known well time 15-120 minutes before anticipated study drug injection&#xD;
&#xD;
          3. Suspected stroke identified by the LAPSS&#xD;
&#xD;
          4. Moderate to severe motor deficit, with Los Angeles Motor Scale (LAMS) 2 or higher&#xD;
&#xD;
          5. No seizure&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Coma&#xD;
&#xD;
          2. Rapidly improving neurologic deficit&#xD;
&#xD;
          3. History of seizures or epilepsy&#xD;
&#xD;
          4. Pre-existing neurologic, psychiatric, or advanced systemic disease that would confound&#xD;
             the neurological or functional outcome evaluations&#xD;
&#xD;
          5. SBP &lt; 90 or &gt; 220&#xD;
&#xD;
          6. Major head trauma in the last 24 hours&#xD;
&#xD;
          7. Recent stroke within 30 days&#xD;
&#xD;
          8. Known to be pregnant or lactating&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrew Southerland, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Virginia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nerses Sanossian, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Southern California</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Karen Johnston, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Virginia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jeffrey Saver, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University of California, Los Angeles</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>December 3, 2018</study_first_submitted>
  <study_first_submitted_qc>December 3, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 4, 2018</study_first_posted>
  <results_first_submitted>May 24, 2021</results_first_submitted>
  <results_first_submitted_qc>May 24, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 18, 2021</results_first_posted>
  <last_update_submitted>May 24, 2021</last_update_submitted>
  <last_update_submitted_qc>May 24, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 2021</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>Stroke</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trans-sodium crocetinate</mesh_term>
  </intervention_browse>
  <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>November 18, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/29/NCT03763929/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Trans Sodium Crocetinate</title>
          <description>Trans sodium crocetinate (TSC) will be administered intravenously as a bolus to subjects randomized to experimental drug. The bolus dose will consist of 0.25 mg/kg of TSC based on the estimated subject weight.&#xD;
Trans-Sodium Crocetinate: In the study drug kit containing the experimental drug (TSC), TSC will be reconstituted with the Sterile Water for Injection (USP) supplied in the same kit. There will be an unblinded paramedic who will reconstitute and inject the TSC on the ambulance.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>The placebo consists of commercially available sterile saline. Placebo will be administered intravenously as a bolus to subjects randomized to placebo. The volume of sterile saline will be based on the estimated subject weight.&#xD;
Placebo: The study drug kit containing placebo (sterile saline for Injection) will be prepared and injected by the unblinded paramedic on the ambulance.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Trans Sodium Crocetinate</title>
          <description>Trans sodium crocetinate (TSC) will be administered intravenously as a bolus to subjects randomized to experimental drug. The bolus dose will consist of 0.25 mg/kg of TSC based on the estimated subject weight.&#xD;
Trans-Sodium Crocetinate: In the study drug kit containing the experimental drug (TSC), TSC will be reconstituted with the Sterile Water for Injection (USP) supplied in the same kit. There will be an unblinded paramedic who will reconstitute and inject the TSC on the ambulance.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>The placebo consists of commercially available sterile saline. Placebo will be administered intravenously as a bolus to subjects randomized to placebo. The volume of sterile saline will be based on the estimated subject weight.&#xD;
Placebo: The study drug kit containing placebo (sterile saline for Injection) will be prepared and injected by the unblinded paramedic on the ambulance.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="2"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="6"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="74.0" lower_limit="73" upper_limit="75"/>
                    <measurement group_id="B2" value="63.8" lower_limit="45" upper_limit="80"/>
                    <measurement group_id="B3" value="67.2" lower_limit="45" upper_limit="80"/>
                  </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="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" 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>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Global Disability Level on the Modified Rankin Score (mRS)</title>
        <description>Modified Rankin Scale (mRS) is a measure of global disability. Total scale range is 0-6, with lower values indicating better outcomes.&#xD;
0 = No symptoms at all&#xD;
= No significant disability despite symptoms; able to carry out all usual duties and activities&#xD;
= Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance&#xD;
= Moderate disability; requiring some help, but able to walk without assistance&#xD;
= Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance&#xD;
= Severe disability; bedridden, incontinent and requiring constant nursing care and attention&#xD;
= Dead</description>
        <time_frame>90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Trans Sodium Crocetinate</title>
            <description>Trans sodium crocetinate (TSC) will be administered intravenously as a bolus to subjects randomized to experimental drug. The bolus dose will consist of 0.25 mg/kg of TSC based on the estimated subject weight.&#xD;
Trans-Sodium Crocetinate: In the study drug kit containing the experimental drug (TSC), TSC will be reconstituted with the Sterile Water for Injection (USP) supplied in the same kit. There will be an unblinded paramedic who will reconstitute and inject the TSC on the ambulance.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>The placebo consists of commercially available sterile saline. Placebo will be administered intravenously as a bolus to subjects randomized to placebo. The volume of sterile saline will be based on the estimated subject weight.&#xD;
Placebo: The study drug kit containing placebo (sterile saline for Injection) will be prepared and injected by the unblinded paramedic on the ambulance.</description>
          </group>
        </group_list>
        <measure>
          <title>Global Disability Level on the Modified Rankin Score (mRS)</title>
          <description>Modified Rankin Scale (mRS) is a measure of global disability. Total scale range is 0-6, with lower values indicating better outcomes.&#xD;
0 = No symptoms at all&#xD;
= No significant disability despite symptoms; able to carry out all usual duties and activities&#xD;
= Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance&#xD;
= Moderate disability; requiring some help, but able to walk without assistance&#xD;
= Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance&#xD;
= Severe disability; bedridden, incontinent and requiring constant nursing care and attention&#xD;
= Dead</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.5" lower_limit="2" upper_limit="3"/>
                    <measurement group_id="O2" value="3.0" lower_limit="0" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected from the start of study drug administration through the end of the Day 90 follow-up visit.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Trans Sodium Crocetinate</title>
          <description>Trans sodium crocetinate (TSC) will be administered intravenously as a bolus to subjects randomized to experimental drug. The bolus dose will consist of 0.25 mg/kg of TSC based on the estimated subject weight.&#xD;
Trans-Sodium Crocetinate: In the study drug kit containing the experimental drug (TSC), TSC will be reconstituted with the Sterile Water for Injection (USP) supplied in the same kit. There will be an unblinded paramedic who will reconstitute and inject the TSC on the ambulance.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>The placebo consists of commercially available sterile saline. Placebo will be administered intravenously as a bolus to subjects randomized to placebo. The volume of sterile saline will be based on the estimated subject weight.&#xD;
Placebo: The study drug kit containing placebo (sterile saline for Injection) will be prepared and injected by the unblinded paramedic on the ambulance.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (Unspecified)</default_vocab>
        <default_assessment>Non-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="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Hemorrhagic Transformation of Infarct</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Cerebral Edema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Respiratory Failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (Unspecified)</default_vocab>
        <default_assessment>Non-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="1" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypochromic Anemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ankle Fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Hemiparesis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary Retention</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Increased Bronchial Secretion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The trial was early terminated after 6 subjects were enrolled due to logistical issues surrounding the COVID-19 pandemic. Due to this low enrollment number, the statistical plan outlined in the protocol was not utilized. Data listings and tables were instead created, which captured data on the 6 subjects in a descriptive manner. Therefore, no substantive conclusions could be drawn.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Clinical Operations</name_or_title>
      <organization>Diffusion Pharmaceuticals Inc</organization>
      <phone>434-220-0718</phone>
      <email>clinicaltrials@diffusionpharma.com</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/NCT03763929
org study id: 100-501
nct id: NCT03763929
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will assess the potential efficacy and safety of TSC as early treatment for both
      ischemic and hemorrhagic stroke when administered while subject is in ambulance being
      transported to hospital.
This is a multicenter, randomized, placebo-controlled, double-blind, parallel group trial of
      intravenous trans sodium crocetinate (TSC) initiated by emergency medical service (EMS)
      responders in the field within 2 hours of symptom onset in 160 subjects with acute stroke.
      The primary objectives of the study are to evaluate the efficacy and safety of
      field-initiated TSC in improving the long-term functional outcome of subjects with acute
      stroke.

      Subjects with acute stroke will be identified and screened in the ambulance by (EMS)
      responders who have received training in basic and advanced cardiac life support, stroke
      recognition, and specific procedures relevant to the proposed study. The EMS responders will
      contact a Study Neurologist, who will enroll eligible stroke patients into the study. Effort
      will be made to obtain prospective informed consent in the ambulance when deemed to be
      feasible. If not feasible, subjects will be enrolled under regulations for exception from
      explicit informed consent (EFIC) in emergency research circumstances, after public disclosure
      and community consultation. Written informed consent to continue in the study is obtained
      from subjects or their legally authorized representatives as soon as possible after hospital
      arrival.

      EMS responders will deliver the single, field, bolus dose of study agent, TSC at 0.25 mg/kg
      or matched placebo, followed after hospital arrival by standard of care (SOC). No additional
      study drug will be administered in the hospital. Follow-up assessments will be performed at
      Emergency Department (ED) arrival, 24 hours, 48 hours, Day 4, Day 30, and Day 90. The study
      will be performed at up to 30 receiving hospital sites in Los Angeles County, CA, and central
      Virginia.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Multicenter, randomized, placebo-controlled, double-blind, parallel group
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: TSC injections will be prepared and injected by unblinded personnel on each ambulance. All other study personnel will be blinded
measure: Global Disability Level on the Modified Rankin Score (mRS)
time frame: 90 days
description: Modified Rankin Scale (mRS) is a measure of global disability. Total scale range is 0-6, with lower values indicating better outcomes.
0 = No symptoms at all
= No significant disability despite symptoms; able to carry out all usual duties and activities
= Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
= Moderate disability; requiring some help, but able to walk without assistance
= Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance
= Severe disability; bedridden, incontinent and requiring constant nursing care and attention
= Dead
arm group label: Trans Sodium Crocetinate
arm group type: Experimental
description: Trans sodium crocetinate (TSC) will be administered intravenously as a bolus to subjects randomized to experimental drug. The bolus dose will consist of 0.25 mg/kg of TSC based on the estimated subject weight.
arm group label: Placebo
arm group type: Placebo Comparator
description: The placebo consists of commercially available sterile saline. Placebo will be administered intravenously as a bolus to subjects randomized to placebo. The volume of sterile saline will be based on the estimated subject weight.
intervention type: Drug
intervention name: Trans-Sodium Crocetinate
description: In the study drug kit containing the experimental drug (TSC), TSC will be reconstituted with the Sterile Water for Injection (USP) supplied in the same kit. There will be an unblinded paramedic who will reconstitute and inject the TSC on the ambulance.
arm group label: Trans Sodium Crocetinate
other name: TSC
intervention type: Other
intervention name: Placebo
description: The study drug kit containing placebo (sterile saline for Injection) will be prepared and injected by the unblinded paramedic on the ambulance.
arm group label: Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: 85 Years
healthy volunteers: No
last name: Andrew Southerland, MD
role: Principal Investigator
affiliation: University of Virginia
last name: Nerses Sanossian, MD
role: Principal Investigator
affiliation: University of Southern California
last name: Karen Johnston, MD
role: Study Chair
affiliation: University of Virginia
last name: Jeffrey Saver, MD
role: Study Chair
affiliation: University of California, Los Angeles
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Stroke
mesh term: Trans-sodium crocetinate
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The trial was early terminated after 6 subjects were enrolled due to logistical issues surrounding the COVID-19 pandemic. Due to this low enrollment number, the statistical plan outlined in the protocol was not utilized. Data listings and tables were instead created, which captured data on the 6 subjects in a descriptive manner. Therefore, no substantive conclusions could be drawn.
point of contact: 