<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/NCT03767192</url>
  </required_header>
  <id_info>
    <org_study_id>CLP1000500-24A</org_study_id>
    <nct_id>NCT03767192</nct_id>
  </id_info>
  <brief_title>Implant for Augmentation of Cerebral Blood Flow Trial, Effectiveness and Safety in a 24 Hour Window (ImpACT-24A)</brief_title>
  <acronym>ImpACT-24A</acronym>
  <official_title>A Multicenter, Randomized, Double Blind, Sham Control, Parallel Arm Trial to Assess Effectiveness and Safety of the Ischemic Stroke System ISS, as an Adjunct to Standard of Care in Subjects With Acute Ischemic Stroke</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BrainsGate</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>BrainsGate</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of the study is to assess the safety and effectiveness of SPG&#xD;
      stimulation with the ISS in patients with an acute ischemic stroke in the anterior&#xD;
      circulation initiated within 24 hours from stroke onset.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study was first registered as NCT00826059 on January 19, 2009 under the name ImpACT-24.&#xD;
&#xD;
      Background:&#xD;
&#xD;
      Recruitment to ImpACT-24 was halted, the protocol was amended and then the study was resumed.&#xD;
      Later, it was decided to define the first part (before the halt) as a separate study -&#xD;
      ImpACT-24A, and identify the continuation of the study as ImpACT-24B. ImpACT-24B continues to&#xD;
      be registered as NCT00826059, and ImpACT-24A is registered in this new record.&#xD;
&#xD;
      Detailed Description:&#xD;
&#xD;
      A multi-center, multinational, randomized, double blind, sham control, adjunctive to Standard&#xD;
      of Care, parallel arm study with ongoing DSMB review of accumulated safety data.&#xD;
&#xD;
      Screening:&#xD;
&#xD;
      Treatment should be initiated between 8 and 24 hours from stroke onset. All screened patients&#xD;
      will be identified by patient number and will sign the informed consent prior to any study&#xD;
      procedure initiation.&#xD;
&#xD;
      Period 1: Day 1-5&#xD;
&#xD;
      Day 1- Eligible subjects will be randomized in a 2:1 (ISS Stimulation: Sham Control) ratio:&#xD;
&#xD;
      Group 1: Implantation and ISS Stimulation during five consecutive days &amp; Standard of Care&#xD;
      Group 2: Implantation and Sham Stimulation during five consecutive days &amp; Standard of Care&#xD;
      The implantation will be performed by a trained physician. Stimulation/sham stimulation will&#xD;
      be delivered Day 2-5 ISS / Sham Stimulation will be repeated during the following four&#xD;
      consecutive days by trained personnel within 18-26 hours from preceding stimulation.&#xD;
&#xD;
      Day 5 / Day of Discharge. Following the last ISS /Sham Stimulation, explantation will be&#xD;
      performed.&#xD;
&#xD;
      Subjects will continue with Standard of Care as needed and will be released from the hospital&#xD;
      upon investigator's judgment.&#xD;
&#xD;
      Period 2: Day of Discharge - 90±7 days During this period both groups (ISS Stimulation and&#xD;
      Sham Control) will be treated according to Standard of Care either at the hospital,&#xD;
      rehabilitation center or at home.&#xD;
&#xD;
      Scheduled visits will be performed on day 30±7 and day 60 ±7, which will include safety and&#xD;
      effectiveness assessments.&#xD;
&#xD;
      Final Visit Day 90±7 days: The final visit will be performed at the study site and will&#xD;
      include safety and effectiveness evaluations.&#xD;
&#xD;
      Patients will be contacted by study personnel via telephone on Day 180±7 and on Day 360±7 in&#xD;
      order to assess their quality of life status.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Protocol Amendment&#xD;
  </why_stopped>
  <start_date type="Actual">January 2009</start_date>
  <completion_date type="Actual">March 2012</completion_date>
  <primary_completion_date type="Actual">January 2011</primary_completion_date>
  <phase>N/A</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Sliding Dichotomy modified Rankin Scale (mRS) at 3 months</measure>
    <time_frame>90 ±7 days</time_frame>
    <description>Final global disability level on the modified Rankin scale (mRS) at 3 months better than expectation (sliding dichotomy analysis) ) assessed in the modified intention to treat (mITT) population defined as all randomized subjects receiving at least the minimal exposure of 1 treatment (ISS Stimulation or Sham Control) session out of the 5 planned sessions.&#xD;
mRS Scale:&#xD;
0 - No symptoms.&#xD;
1 - No significant disability. Able to carry out all usual activities, despite some symptoms.&#xD;
2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.&#xD;
3 - Moderate disability. Requires some help, but able to walk unassisted.&#xD;
4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.&#xD;
5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.&#xD;
6 - Dead.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with Serious Adverse Events</measure>
    <time_frame>90 ±7 days</time_frame>
    <description>Comparison between the active and sham stimulation groups of all serious adverse events (SAEs)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with neurological deterioration</measure>
    <time_frame>10 days</time_frame>
    <description>Comparison between the active and sham stimulation groups of the rate of neurological deterioration, defined as an increase of 4 or more points on the NIHSS related to any neurological event within the first 10 days after stroke onset</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with implantation complications</measure>
    <time_frame>90 ±7 days</time_frame>
    <description>The rate of implantation complications as classified by the investigator</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with stimulation-related adverse events</measure>
    <time_frame>90 ±7 days</time_frame>
    <description>Comparison between the active and sham stimulation groups of stimulation-related adverse events as classified by the investigator</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mortality rate</measure>
    <time_frame>90 ±7 days</time_frame>
    <description>Comparison of mortality rates between the active and sham stimulation groups</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sliding Dichotomous 90-day mRS for patients with Aphasia at baseline</measure>
    <time_frame>90 ±7 days</time_frame>
    <description>Sliding Dichotomous 90-day mRS for patients with Aphasia at baseline&#xD;
mRS Scale:&#xD;
0 - No symptoms.&#xD;
1 - No significant disability. Able to carry out all usual activities, despite some symptoms.&#xD;
2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.&#xD;
3 - Moderate disability. Requires some help, but able to walk unassisted.&#xD;
4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.&#xD;
5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.&#xD;
6 - Dead.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Binary NIHSS at Day 90</measure>
    <time_frame>90 ±7 days</time_frame>
    <description>Binary NIHSS (success for score ≤1 or for ≥ 9-point improvement versus baseline)&#xD;
The NIHSS (National Institute of Health Stroke Score) is a 42-point scale that quantifies neurological deficits in 11 categories. Ratings for each item are scored with 3 to 5 grades, with 0 as normal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stroke-related quality of life at 3 months: Stroke Impact Scale-16</measure>
    <time_frame>90 ±7 days</time_frame>
    <description>Stroke-related quality of life at 3 months according to the Stroke Impact Scale-16 (SIS-16)&#xD;
The scale is based on a questionnaire with 16 items. Each answer ranges from 1 (poor) to 5 (good). A final single-item Recovery domain assesses the individual's perception of his/her recovery from stroke, where:&#xD;
0 = no recovery 100 = full recovery.&#xD;
Domain scores range from 0-100 and are calculated using the following equation:&#xD;
Domain score = [(Mean item score - 1) / (5-1) ] x 100</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">327</enrollment>
  <condition>Acute Ischemic Stroke</condition>
  <arm_group>
    <arm_group_label>Active Stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Device: The Ischemic Stroke System SPG stimulation and standard of care</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham Stimulation</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Device: Sham control Sham stimulation and standard of care</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Active Stimulation</intervention_name>
    <description>SPG stimulation and standard of care</description>
    <arm_group_label>Active Stimulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham Stimulation</intervention_name>
    <description>Sham SPG stimulation and standard of care</description>
    <arm_group_label>Sham Stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age: ≥ 18 years and ≤ 85 of both genders.&#xD;
&#xD;
          2. Clinical diagnosis of an acute ischemic stroke in the Carotid, Middle or Anterior&#xD;
             Cerebral Artery territories&#xD;
&#xD;
          3. Baseline NIHSS ≥ 7 and ≤ 18&#xD;
&#xD;
          4. Ability to initiate treatment within 8- 24 hours from stroke onset.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Intracranial hemorrhage or hemorrhagic transformation&#xD;
&#xD;
          2. Massive stroke&#xD;
&#xD;
          3. Acute ischemic stroke in the posterior circulation&#xD;
&#xD;
          4. Minor stroke&#xD;
&#xD;
          5. Treated with IV-tPA ,IA-tPA or neurothrombectomy devices for the current stroke&#xD;
&#xD;
          6. Previous stroke in the last 6 months or pre-existing disability&#xD;
&#xD;
          7. Patients with bleeding propensity or any condition in the oral cavity that prevents&#xD;
             implantation&#xD;
&#xD;
          8. Known cerebral arteriovenous malformation, cerebral aneurysm.&#xD;
&#xD;
          9. Clinical suspicion of septic embolus.&#xD;
&#xD;
         10. Uncontrolled hypertension (systolic &gt;185 mmHg and/or diastolic &gt;110 mmHg)&#xD;
&#xD;
         11. Serious systemic infection.&#xD;
&#xD;
         12. Women known to be pregnant or having a positive or indeterminate pregnancy test.&#xD;
&#xD;
         13. Patients with other implanted neural stimulator/ electronic devices (pacemakers).&#xD;
&#xD;
         14. Life expectancy &lt; 1 year from causes other than stroke.&#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>Eyal Shay</last_name>
    <role>Study Director</role>
    <affiliation>BrainsGate</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Erlanger Stroke Center</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erlangen University Clinic</name>
      <address>
        <city>Erlangen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Essen University Clinic</name>
      <address>
        <city>Essen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Heidelberg University Clinic</name>
      <address>
        <city>Heidelberg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leipzig University Clinic</name>
      <address>
        <city>Leipzig</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Munster University Clinic</name>
      <address>
        <city>Münster</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari de Girona</name>
      <address>
        <city>Girona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 5, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 6, 2018</study_first_posted>
  <last_update_submitted>January 25, 2019</last_update_submitted>
  <last_update_submitted_qc>January 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 28, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>acute ischemic stroke</keyword>
  <keyword>randomized clinical trial</keyword>
  <keyword>effectiveness</keyword>
  <keyword>safety</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>Ischemia</mesh_term>
  </condition_browse>
  <!-- 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/NCT03767192
org study id: CLP1000500-24A
nct id: NCT03767192
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
The primary objective of the study is to assess the safety and effectiveness of SPG
      stimulation with the ISS in patients with an acute ischemic stroke in the anterior
      circulation initiated within 24 hours from stroke onset.
This study was first registered as NCT00826059 on January 19, 2009 under the name ImpACT-24.

      Background:

      Recruitment to ImpACT-24 was halted, the protocol was amended and then the study was resumed.
      Later, it was decided to define the first part (before the halt) as a separate study -
      ImpACT-24A, and identify the continuation of the study as ImpACT-24B. ImpACT-24B continues to
      be registered as NCT00826059, and ImpACT-24A is registered in this new record.

      Detailed Description:

      A multi-center, multinational, randomized, double blind, sham control, adjunctive to Standard
      of Care, parallel arm study with ongoing DSMB review of accumulated safety data.

      Screening:

      Treatment should be initiated between 8 and 24 hours from stroke onset. All screened patients
      will be identified by patient number and will sign the informed consent prior to any study
      procedure initiation.

      Period 1: Day 1-5

      Day 1- Eligible subjects will be randomized in a 2:1 (ISS Stimulation: Sham Control) ratio:

      Group 1: Implantation and ISS Stimulation during five consecutive days & Standard of Care
      Group 2: Implantation and Sham Stimulation during five consecutive days & Standard of Care
      The implantation will be performed by a trained physician. Stimulation/sham stimulation will
      be delivered Day 2-5 ISS / Sham Stimulation will be repeated during the following four
      consecutive days by trained personnel within 18-26 hours from preceding stimulation.

      Day 5 / Day of Discharge. Following the last ISS /Sham Stimulation, explantation will be
      performed.

      Subjects will continue with Standard of Care as needed and will be released from the hospital
      upon investigator's judgment.

      Period 2: Day of Discharge - 90±7 days During this period both groups (ISS Stimulation and
      Sham Control) will be treated according to Standard of Care either at the hospital,
      rehabilitation center or at home.

      Scheduled visits will be performed on day 30±7 and day 60 ±7, which will include safety and
      effectiveness assessments.

      Final Visit Day 90±7 days: The final visit will be performed at the study site and will
      include safety and effectiveness evaluations.

      Patients will be contacted by study personnel via telephone on Day 180±7 and on Day 360±7 in
      order to assess their quality of life status.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Sliding Dichotomy modified Rankin Scale (mRS) at 3 months
time frame: 90 ±7 days
description: Final global disability level on the modified Rankin scale (mRS) at 3 months better than expectation (sliding dichotomy analysis) ) assessed in the modified intention to treat (mITT) population defined as all randomized subjects receiving at least the minimal exposure of 1 treatment (ISS Stimulation or Sham Control) session out of the 5 planned sessions.
mRS Scale:
0 - No symptoms.
1 - No significant disability. Able to carry out all usual activities, despite some symptoms.
2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
3 - Moderate disability. Requires some help, but able to walk unassisted.
4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
6 - Dead.
measure: Number of participants with Serious Adverse Events
time frame: 90 ±7 days
description: Comparison between the active and sham stimulation groups of all serious adverse events (SAEs)
measure: Number of participants with neurological deterioration
time frame: 10 days
description: Comparison between the active and sham stimulation groups of the rate of neurological deterioration, defined as an increase of 4 or more points on the NIHSS related to any neurological event within the first 10 days after stroke onset
measure: Number of participants with implantation complications
time frame: 90 ±7 days
description: The rate of implantation complications as classified by the investigator
measure: Number of participants with stimulation-related adverse events
time frame: 90 ±7 days
description: Comparison between the active and sham stimulation groups of stimulation-related adverse events as classified by the investigator
measure: Mortality rate
time frame: 90 ±7 days
description: Comparison of mortality rates between the active and sham stimulation groups
measure: Sliding Dichotomous 90-day mRS for patients with Aphasia at baseline
time frame: 90 ±7 days
description: Sliding Dichotomous 90-day mRS for patients with Aphasia at baseline
mRS Scale:
0 - No symptoms.
1 - No significant disability. Able to carry out all usual activities, despite some symptoms.
2 - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
3 - Moderate disability. Requires some help, but able to walk unassisted.
4 - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
5 - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
6 - Dead.
measure: Binary NIHSS at Day 90
time frame: 90 ±7 days
description: Binary NIHSS (success for score ≤1 or for ≥ 9-point improvement versus baseline)
The NIHSS (National Institute of Health Stroke Score) is a 42-point scale that quantifies neurological deficits in 11 categories. Ratings for each item are scored with 3 to 5 grades, with 0 as normal.
measure: Stroke-related quality of life at 3 months: Stroke Impact Scale-16
time frame: 90 ±7 days
description: Stroke-related quality of life at 3 months according to the Stroke Impact Scale-16 (SIS-16)
The scale is based on a questionnaire with 16 items. Each answer ranges from 1 (poor) to 5 (good). A final single-item Recovery domain assesses the individual's perception of his/her recovery from stroke, where:
0 = no recovery 100 = full recovery.
Domain scores range from 0-100 and are calculated using the following equation:
Domain score = [(Mean item score - 1) / (5-1) ] x 100
arm group label: Active Stimulation
arm group type: Experimental
description: Device: The Ischemic Stroke System SPG stimulation and standard of care
arm group label: Sham Stimulation
arm group type: Sham Comparator
description: Device: Sham control Sham stimulation and standard of care
intervention type: Device
intervention name: Active Stimulation
description: SPG stimulation and standard of care
arm group label: Active Stimulation
intervention type: Device
intervention name: Sham Stimulation
description: Sham SPG stimulation and standard of care
arm group label: Sham Stimulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Eyal Shay
role: Study Director
affiliation: BrainsGate
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
country: Spain
country: United States
responsible party type: Sponsor
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Ischemia