<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/NCT02235558</url>
  </required_header>
  <id_info>
    <org_study_id>12-0975-F1V</org_study_id>
    <nct_id>NCT02235558</nct_id>
  </id_info>
  <brief_title>Superselective Administration of VErapamil During Recanalization in Acute Ischemic Stroke</brief_title>
  <acronym>SAVER-I</acronym>
  <official_title>Super-Selective Intra-Arterial Administration of Verapamil for Neuroprotection After Intra-Arterial Thrombolysis for Acute Ischemic Stroke Phase I Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Justin Fraser</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Kentucky</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</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>
      The purpose of this study is to determine whether super-selective intra-arterial&#xD;
      administration of verapamil immediately following successful intra-arterial thrombolysis is&#xD;
      safe as a potential neuroprotective agent. Standard procedures are cerebral angiography and&#xD;
      intra-arterial thrombolysis (intra-arterial administration of tPA and/or mechanical&#xD;
      thrombectomy). Experimental procedure is superselective injection of verapamil&#xD;
      intra-arterially.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This trial represents the first time that verapamil will be evaluated in human subjects as a&#xD;
      superselectively administered neuroprotective agent administered in an acute time frame as an&#xD;
      adjunct to intra-arterial thrombolysis. The methods for administration, along with the&#xD;
      routinized followup, will provide a paradigm for studying other potential neuroprotective&#xD;
      agents. Subjects will undergo cerebral angiography with intra-arterial thrombolysis, which is&#xD;
      standard of care. 'Intra-arterial thrombolysis will include possible intra-arterial&#xD;
      administration of tPA, as well as possible mechanical thrombectomy with an accepted&#xD;
      thrombectomy device. This includes the Mercí Retriever (Concentric Medical, Mountain View,&#xD;
      CA), the Penumbra System (Penumbra, Alameda, CA), the Solitaire stent-triever (EV3, Covidien,&#xD;
      Irvine, CA), and the Trevo stent-triever (Concentric Medical, Mountain View, CA). Immediately&#xD;
      after the intra-arterial thrombolysis component of the angiographic procedure is completed,&#xD;
      the microcatheter used during the procedure will be left in or guided into the vessel&#xD;
      location of the clot. 10mg of verapamil in 20cc of normal saline will be administered over 20&#xD;
      minutes (1cc/minute) through the microcatheter and into the vessel previously obstructed by&#xD;
      clot. At the conclusion of infusion, the microcatheter will be removed. Angiography through&#xD;
      the guide catheter of the cerebral circulation in question will be performed to ensure no new&#xD;
      thromboembolic event from the microcatheterization (standard of care). The catheters will be&#xD;
      removed, and the arterial puncture site closed in the standard fashion. Patients will receive&#xD;
      a noncontrast CT scan or MRI approximately 24 hours after intervention to determine the&#xD;
      presence or absence of intracerebral hemorrhage (ICH) after intervention. This would be&#xD;
      considered standard practice for intra-arterial thrombolysis. Both imaging studies can detect&#xD;
      ICH, and the choice of one or the other will be determined by clinical criteria; CT or MRI&#xD;
      may be preferable for different reasons depending upon the patient's clinical scenario. The&#xD;
      determination of hemorrhage will be made by the official dictation of a diagnostic&#xD;
      neuroradiologist not directly involved in the study. The hemorrhage will be considered an&#xD;
      adverse event if it is deemed symptomatic in accordance with the criteria used in the&#xD;
      International Management of Stroke (IMS) III study. Briefly, a hemorrhage is defined as&#xD;
      symptomatic if occurring within 24+/-6 hours after study inclusion, temporally related to the&#xD;
      intervention, and occurs with worsening neurological status as documented in the clinical&#xD;
      exam. A 4 point or more increase in the NIHSS stroke scale would qualify as a significant&#xD;
      worsening in status. Furthermore, hemorrhage that requires intervention surgically or&#xD;
      endovascularly would be deemed significant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2013</start_date>
  <completion_date type="Actual">March 21, 2016</completion_date>
  <primary_completion_date type="Actual">March 21, 2016</primary_completion_date>
  <phase>Phase 1</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Open Label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>The primary endpoint will be the presence or absence of intracranial hemorrhage</measure>
    <time_frame>24-48 hours after treatment</time_frame>
    <description>Patients will receive a noncontrast CT scan or MRI approximately 24 hours after intervention to determine the presence or absence of intracerebral hemorrhage (ICH) after intervention.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Absence of intracranial hemorrhage</measure>
    <time_frame>At follow-up intervals: Day 30 ± 14 days, 3 Months ± 30 days, 6 Months ± 30 days, 12 Months± 30 days</time_frame>
    <description>Improved clinical outcomes at followup intervals as measured by the modified Rankin score.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Absence of systemic side effects of verapamil administration</measure>
    <time_frame>24-48 hours</time_frame>
    <description>Patients will receive a noncontrast CT scan or MRI approximately 24 hours after intervention to determine the presence or absence of intracerebral hemorrhage (ICH) after intervention.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Ischemic Stroke</condition>
  <arm_group>
    <arm_group_label>Verapamil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Super-selective intra-arterial administration of 10 mg verapamil immediately following successful intra-arterial thrombolysis</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Verapamil</intervention_name>
    <description>Super-selective intra-arterial administration of 10mg verapamil in 20cc of normal saline will be administered over 20 minutes (1cc/minute) through the microcatheter and into the vessel previously obstructed by clot, immediately following successful intra-arterial thrombolysis. Half-life is 2.8-7.4 hrs.</description>
    <arm_group_label>Verapamil</arm_group_label>
    <other_name>Isoptin</other_name>
    <other_name>Verelan</other_name>
    <other_name>Verelan PM</other_name>
    <other_name>Calan</other_name>
    <other_name>Bosoptin</other_name>
    <other_name>Calaptin</other_name>
    <other_name>Covera-HS</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients 21-85 years old, male or female&#xD;
&#xD;
          2. Suspected acute ischemic stroke based on clinical and radiographic evidence as&#xD;
             determined and documented by the Stroke Neurology team at University of Kentucky.&#xD;
&#xD;
          3. Patients must meet criteria for intra-arterial thrombolysis as determined and&#xD;
             documented by Interventional Neuroradiology attending physician (JF or AA).&#xD;
&#xD;
          4. Patients must have an acute thromboembolus within an intracranial artery (internal&#xD;
             carotid, anterior cerebral, middle cerebral, posterior cerebral, basilar, vertebral)&#xD;
             which undergoes pharmacologic (tissue plasminogen activator - tPA) and/or mechanical&#xD;
             (eg. Merci or Penumbra clot retrieval) thrombolysis.&#xD;
&#xD;
          5. Patients with impaired capacity may be included, as the pathology to be studied&#xD;
             (stroke) may impair their capacity (please see attached required documentation&#xD;
             regarding impaired capacity).&#xD;
&#xD;
          6. Patients must have a TICI 2A or better revascularization via intra-arterial&#xD;
             thrombolysis.&#xD;
&#xD;
        For reference, the TICI Scale is defined below:&#xD;
&#xD;
        0 = No Perfusion&#xD;
&#xD;
          1. = Perfusion past the initial obstruction but limited distal branch filling with little&#xD;
             or slow distal perfusion&#xD;
&#xD;
          2. A = Perfusion of less than 50% of the vascular distribution of the occluded artery&#xD;
&#xD;
        2B = Perfusion of 50% or greater (but not complete) of the vascular distribution of the&#xD;
        occluded artery 3 = Full perfusion with filling of all distal branches&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Pregnant women (would not qualify for intra-arterial thrombolysis as standard of&#xD;
             care).&#xD;
&#xD;
          2. Patients who undergo intra-arterial thrombolysis for acute stroke, in whom only TICI 0&#xD;
             or 1 revascularization is obtained.&#xD;
&#xD;
          3. Patients with occlusion of the cervical common or internal carotid artery will be&#xD;
             excluded from the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Justin F. Fraser, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Kentucky Department of Neurological Surgery</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Kentucky Deparment of Neurosurgery, UK Chandler Hospital</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>September 7, 2014</study_first_submitted>
  <study_first_submitted_qc>September 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2014</study_first_posted>
  <last_update_submitted>January 19, 2017</last_update_submitted>
  <last_update_submitted_qc>January 19, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 23, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Kentucky</investigator_affiliation>
    <investigator_full_name>Justin Fraser</investigator_full_name>
    <investigator_title>Asst Professor of Cerebrovascular, Endovascular, and Skull Base Surgery; Departments of Neurological Surgery, Neurology, Radiology, and Anatomy &amp; Neurobiology</investigator_title>
  </responsible_party>
  <keyword>Acute Ischemic Stoke</keyword>
  <keyword>Thrombectomy</keyword>
  <keyword>Intraarterial Pharmacotherapy</keyword>
  <keyword>Neuroprotection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Ischemic Stroke</mesh_term>
    <mesh_term>Cerebral Infarction</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Verapamil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02235558
org study id: 12-0975-F1V
nct id: NCT02235558
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is to determine whether super-selective intra-arterial
      administration of verapamil immediately following successful intra-arterial thrombolysis is
      safe as a potential neuroprotective agent. Standard procedures are cerebral angiography and
      intra-arterial thrombolysis (intra-arterial administration of tPA and/or mechanical
      thrombectomy). Experimental procedure is superselective injection of verapamil
      intra-arterially.
This trial represents the first time that verapamil will be evaluated in human subjects as a
      superselectively administered neuroprotective agent administered in an acute time frame as an
      adjunct to intra-arterial thrombolysis. The methods for administration, along with the
      routinized followup, will provide a paradigm for studying other potential neuroprotective
      agents. Subjects will undergo cerebral angiography with intra-arterial thrombolysis, which is
      standard of care. 'Intra-arterial thrombolysis will include possible intra-arterial
      administration of tPA, as well as possible mechanical thrombectomy with an accepted
      thrombectomy device. This includes the Mercí Retriever (Concentric Medical, Mountain View,
      CA), the Penumbra System (Penumbra, Alameda, CA), the Solitaire stent-triever (EV3, Covidien,
      Irvine, CA), and the Trevo stent-triever (Concentric Medical, Mountain View, CA). Immediately
      after the intra-arterial thrombolysis component of the angiographic procedure is completed,
      the microcatheter used during the procedure will be left in or guided into the vessel
      location of the clot. 10mg of verapamil in 20cc of normal saline will be administered over 20
      minutes (1cc/minute) through the microcatheter and into the vessel previously obstructed by
      clot. At the conclusion of infusion, the microcatheter will be removed. Angiography through
      the guide catheter of the cerebral circulation in question will be performed to ensure no new
      thromboembolic event from the microcatheterization (standard of care). The catheters will be
      removed, and the arterial puncture site closed in the standard fashion. Patients will receive
      a noncontrast CT scan or MRI approximately 24 hours after intervention to determine the
      presence or absence of intracerebral hemorrhage (ICH) after intervention. This would be
      considered standard practice for intra-arterial thrombolysis. Both imaging studies can detect
      ICH, and the choice of one or the other will be determined by clinical criteria; CT or MRI
      may be preferable for different reasons depending upon the patient's clinical scenario. The
      determination of hemorrhage will be made by the official dictation of a diagnostic
      neuroradiologist not directly involved in the study. The hemorrhage will be considered an
      adverse event if it is deemed symptomatic in accordance with the criteria used in the
      International Management of Stroke (IMS) III study. Briefly, a hemorrhage is defined as
      symptomatic if occurring within 24+/-6 hours after study inclusion, temporally related to the
      intervention, and occurs with worsening neurological status as documented in the clinical
      exam. A 4 point or more increase in the NIHSS stroke scale would qualify as a significant
      worsening in status. Furthermore, hemorrhage that requires intervention surgically or
      endovascularly would be deemed significant.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Open Label
measure: The primary endpoint will be the presence or absence of intracranial hemorrhage
time frame: 24-48 hours after treatment
description: Patients will receive a noncontrast CT scan or MRI approximately 24 hours after intervention to determine the presence or absence of intracerebral hemorrhage (ICH) after intervention.
measure: Absence of intracranial hemorrhage
time frame: At follow-up intervals: Day 30 ± 14 days, 3 Months ± 30 days, 6 Months ± 30 days, 12 Months± 30 days
description: Improved clinical outcomes at followup intervals as measured by the modified Rankin score.
measure: Absence of systemic side effects of verapamil administration
time frame: 24-48 hours
description: Patients will receive a noncontrast CT scan or MRI approximately 24 hours after intervention to determine the presence or absence of intracerebral hemorrhage (ICH) after intervention.
arm group label: Verapamil
arm group type: Experimental
description: Super-selective intra-arterial administration of 10 mg verapamil immediately following successful intra-arterial thrombolysis
intervention type: Drug
intervention name: Verapamil
description: Super-selective intra-arterial administration of 10mg verapamil in 20cc of normal saline will be administered over 20 minutes (1cc/minute) through the microcatheter and into the vessel previously obstructed by clot, immediately following successful intra-arterial thrombolysis. Half-life is 2.8-7.4 hrs.
arm group label: Verapamil
other name: Isoptin
other name: Verelan
other name: Verelan PM
other name: Calan
other name: Bosoptin
other name: Calaptin
other name: Covera-HS
criteria: 
gender: All
minimum age: 21 Years
maximum age: 85 Years
healthy volunteers: No
last name: Justin F. Fraser, MD
role: Principal Investigator
affiliation: University of Kentucky Department of Neurological Surgery
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Kentucky
investigator full name: Justin Fraser
investigator title: Asst Professor of Cerebrovascular, Endovascular, and Skull Base Surgery; Departments of Neurological Surgery, Neurology, Radiology, and Anatomy & Neurobiology
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Cerebral Infarction
mesh term: Ischemia
mesh term: Verapamil
sharing ipd: No