<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/NCT03290053</url>
  </required_header>
  <id_info>
    <org_study_id>CE-5S</org_study_id>
    <nct_id>NCT03290053</nct_id>
  </id_info>
  <brief_title>Contrast Enhanced Sonothrombolysis and Sonolysis in Stroke - a Swedish Study (CE-5S)</brief_title>
  <acronym>CE-5S</acronym>
  <official_title>Contrast Enhanced Sonothrombolysis and Sonolysis in Stroke - a Swedish Study (CE-5S)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Umeå University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Umeå University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with acute ischemic stroke in anterior circulation within 4,5 hours of symptom&#xD;
      onset, has a bone window and Trombolysis In Brain Ischemia (TIBI) &lt;=4 in a relevant artery&#xD;
      eligible. Both patients receiving thrombolysis and those who do not due to contraindications&#xD;
      such as anticoagulation or recent surgery are enrolled, but into different study arms (CE-5S&#xD;
      A for thrombolysis and B for non-thrombolysis); the decision to treat with thrombolysis or&#xD;
      not is done according to clinical routine.&#xD;
&#xD;
      All included patients are randomized to receive transcranial ultrasound and SonoVue-infusion&#xD;
      or sham-ultrasound and placebo; i.e. in CE-5S A, contrast enhanced sonothrombolysis is&#xD;
      compared to thrombolysis and in CE-5S B, contrast enhanced sonolysis is compared with&#xD;
      conservative management.&#xD;
&#xD;
      Main outcome is improvement in National Institute of Health Stroke Scale (NIHSS) at 24 hours&#xD;
      compared to baseline. Main safety outcome is symptomatic intracerebral haemorrhage.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Poor inclusion rate &amp; lack of funding&#xD;
  </why_stopped>
  <start_date type="Actual">November 28, 2017</start_date>
  <completion_date type="Actual">April 18, 2018</completion_date>
  <primary_completion_date type="Actual">April 18, 2018</primary_completion_date>
  <phase>Phase 3</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Early clinical Outcome defined as change in NIHSS at 24 hours.</measure>
    <time_frame>24 hours</time_frame>
    <description>Change in National NIHSS at 24 hours. Defined reaching of primary endpoint is post-treatment 0 Points and/or improves with &gt;=4 Points compared to pre-treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety: Symptomatic Cerebral Hemorrhage (sICH)</measure>
    <time_frame>24-36 hours</time_frame>
    <description>Assessed with routine post-treatment CT head and requires an accompanied &gt;=4 Points worsening on NIHSS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long term outcome defined as residual handicap at Three months</measure>
    <time_frame>90 days</time_frame>
    <description>90-days modified Rankin Scale (mRS) reaching 0-1.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Ischemic Stroke</condition>
  <arm_group>
    <arm_group_label>CE-5S A: Treatment arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Gets thrombolysis, transcranial ultrasound on the flow limitation and SonoVue infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CE-5S A: Control arm</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Gets thrombolysis, sham transcranial ultrasound and placebo (NaCl) infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CE-5S B: Treatment arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Gets NO thrombolysis (due to contraindications), transcranial ultrasound on the flow limitation and SonoVue infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CE-5S B: Control arm</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Gets NO thrombolysis (due to contraindications), sham transcranial ultrasound and placebo (NaCl) infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SonoVue</intervention_name>
    <description>SonoVue-infusion over 1 hour</description>
    <arm_group_label>CE-5S A: Treatment arm</arm_group_label>
    <arm_group_label>CE-5S B: Treatment arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sodium chloride</intervention_name>
    <description>Placebo</description>
    <arm_group_label>CE-5S A: Control arm</arm_group_label>
    <arm_group_label>CE-5S B: Control arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Transcranial Ultrasound</intervention_name>
    <description>Transcranial ultrasound aimed at the blockage</description>
    <arm_group_label>CE-5S A: Treatment arm</arm_group_label>
    <arm_group_label>CE-5S B: Treatment arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Sham Transcranial Ultrasound</intervention_name>
    <description>Placebo - machine is attached, but not active</description>
    <arm_group_label>CE-5S A: Control arm</arm_group_label>
    <arm_group_label>CE-5S B: Control arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female patients ≥18 years with acute ischaemic stroke in the anterior&#xD;
             circulation, who has given written consent for his/her participation to the study.&#xD;
&#xD;
          -  Remaining neurological deficit that is ≥1 NIHSS points, sufficient to warrant&#xD;
             treatment with tPA (not taking possible contraindications into account) and is severe&#xD;
             enough that possible improvement is clearly analysable&#xD;
&#xD;
          -  Treatment &lt;4½ hours of symptom onset or of waking up in the morning with symptoms&#xD;
&#xD;
          -  Sufficient bone window for acceptable or better acquisition of flow information with&#xD;
             ultrasound with TIBI ≤ 4 in the symptomatic artery&#xD;
&#xD;
          -  In cases with women of Childbearing Capacity (WOCBC): Only if willing to comply with&#xD;
             effective contraception methods during the course of the trial. Acceptable methods are&#xD;
             such as oral contraceptives, contraceptive patches, contraceptive implant, vaginal&#xD;
             contraceptive, double-barrier methods (for example, condom and spermicide),&#xD;
             intrauterine device (IUD), hormonal IUD&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with premorbid modified Rankin Scale (mRS) score ≥3;&#xD;
&#xD;
          -  Patients for whom a complete NIHSS cannot be obtained;&#xD;
&#xD;
          -  Hemiplegic migraine with no arterial occlusion on baseline Computed Tomography of&#xD;
             brain (CT);&#xD;
&#xD;
          -  Seizure at stroke onset and no visible occlusion on baseline CT;&#xD;
&#xD;
          -  Intracranial haemorrhage on baseline CT;&#xD;
&#xD;
          -  Clinical presentation suggesting subarachnoid haemorrhage even if baseline CT is&#xD;
             normal;&#xD;
&#xD;
          -  Large areas of hypodense ischaemic changes on baseline CT;&#xD;
&#xD;
          -  Pregnancy or breast-feeding, pericarditis; sepsis; any other serious medical illness&#xD;
             likely to interact with treatment; confounding pre-existent neurological or&#xD;
             psychiatric disease; unlikely to complete follow-up; any investigational drug &lt;14&#xD;
             days;&#xD;
&#xD;
          -  Inability to provide informed consent sufficiently clearly that the study physician&#xD;
             can be convinced that informed consent has been given by the patient - such as severe&#xD;
             aphasia or coma.&#xD;
&#xD;
        Specific sonothrombolysis exclusion criteria&#xD;
&#xD;
          -  known hypersensitivity/allergy to SonoVue;&#xD;
&#xD;
          -  recent or unstable coronary ischemia or resting angina &lt;7 days;&#xD;
&#xD;
          -  acute cardiac insufficiency, cardiac insufficiency class III/IV; serious cardiac&#xD;
             arrhythmias;&#xD;
&#xD;
          -  any right-left-shunt; severe pulmonary hypertension; uncontrolled hypertension;&#xD;
&#xD;
          -  moderate to severe Chronic Obstructive Pulmonary Disease (COPD; baseline O2 saturation&#xD;
             &lt;80%);&#xD;
&#xD;
          -  acute respiratory distress syndrome (ARDS);&#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>Elias Johansson, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Umeå University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital</name>
      <address>
        <city>Umeå</city>
        <state>Västerbotten</state>
        <zip>90821</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>September 14, 2017</study_first_submitted>
  <study_first_submitted_qc>September 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 21, 2017</study_first_posted>
  <last_update_submitted>May 4, 2018</last_update_submitted>
  <last_update_submitted_qc>May 4, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 11, 2018</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>
    <mesh_term>Ischemic Stroke</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03290053
org study id: CE-5S
nct id: NCT03290053
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Patients with acute ischemic stroke in anterior circulation within 4,5 hours of symptom
      onset, has a bone window and Trombolysis In Brain Ischemia (TIBI) <=4 in a relevant artery
      eligible. Both patients receiving thrombolysis and those who do not due to contraindications
      such as anticoagulation or recent surgery are enrolled, but into different study arms (CE-5S
      A for thrombolysis and B for non-thrombolysis); the decision to treat with thrombolysis or
      not is done according to clinical routine.

      All included patients are randomized to receive transcranial ultrasound and SonoVue-infusion
      or sham-ultrasound and placebo; i.e. in CE-5S A, contrast enhanced sonothrombolysis is
      compared to thrombolysis and in CE-5S B, contrast enhanced sonolysis is compared with
      conservative management.

      Main outcome is improvement in National Institute of Health Stroke Scale (NIHSS) at 24 hours
      compared to baseline. Main safety outcome is symptomatic intracerebral haemorrhage.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Early clinical Outcome defined as change in NIHSS at 24 hours.
time frame: 24 hours
description: Change in National NIHSS at 24 hours. Defined reaching of primary endpoint is post-treatment 0 Points and/or improves with >=4 Points compared to pre-treatment.
measure: Safety: Symptomatic Cerebral Hemorrhage (sICH)
time frame: 24-36 hours
description: Assessed with routine post-treatment CT head and requires an accompanied >=4 Points worsening on NIHSS.
measure: Long term outcome defined as residual handicap at Three months
time frame: 90 days
description: 90-days modified Rankin Scale (mRS) reaching 0-1.
arm group label: CE-5S A: Treatment arm
arm group type: Experimental
description: Gets thrombolysis, transcranial ultrasound on the flow limitation and SonoVue infusion
arm group label: CE-5S A: Control arm
arm group type: Sham Comparator
description: Gets thrombolysis, sham transcranial ultrasound and placebo (NaCl) infusion
arm group label: CE-5S B: Treatment arm
arm group type: Experimental
description: Gets NO thrombolysis (due to contraindications), transcranial ultrasound on the flow limitation and SonoVue infusion
arm group label: CE-5S B: Control arm
arm group type: Sham Comparator
description: Gets NO thrombolysis (due to contraindications), sham transcranial ultrasound and placebo (NaCl) infusion
intervention type: Drug
intervention name: SonoVue
description: SonoVue-infusion over 1 hour
arm group label: CE-5S A: Treatment arm
arm group label: CE-5S B: Treatment arm
intervention type: Drug
intervention name: Sodium chloride
description: Placebo
arm group label: CE-5S A: Control arm
arm group label: CE-5S B: Control arm
intervention type: Procedure
intervention name: Transcranial Ultrasound
description: Transcranial ultrasound aimed at the blockage
arm group label: CE-5S A: Treatment arm
arm group label: CE-5S B: Treatment arm
intervention type: Procedure
intervention name: Sham Transcranial Ultrasound
description: Placebo - machine is attached, but not active
arm group label: CE-5S A: Control arm
arm group label: CE-5S B: Control arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Elias Johansson, MD, PhD
role: Principal Investigator
affiliation: Umeå University
facility: 
country: Sweden
responsible party type: Sponsor
mesh term: Stroke
mesh term: Ischemic Stroke
sharing ipd: Undecided