<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/NCT02190500</url>
  </required_header>
  <id_info>
    <org_study_id>HSC 13-0322</org_study_id>
    <nct_id>NCT02190500</nct_id>
  </id_info>
  <brief_title>BEnefits of Stroke Treatment Delivered Using a Mobile Stroke Unit</brief_title>
  <acronym>BEST-MSU</acronym>
  <official_title>BEnefits of Stroke Treatment Delivered Using a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services:The BEST-MSU Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Hermann Health System</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The University of Texas Health Science Center, Houston</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Baylor College of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>CHI St. Luke's Health, Texas</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>City of Houston Fire Department</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Methodist Hospital Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>West University Fire Department</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>City of Bellaire Fire Department</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ben Taub Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Harris Health</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Patient-Centered Outcomes Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Memorial Hermann Health System</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary goal of this project is to carry out a trial comparing pre-hospital diagnosis and&#xD;
      treatment of patients with stroke symptoms using a Mobile Stroke Unit (MSU) with subsequent&#xD;
      transfer to a Comprehensive Stroke Center (CSC) Emergency Department (ED) for further&#xD;
      management, to standard pre-hospital triage and transport by Emergency Medical Services (EMS)&#xD;
      to a CSC ED for evaluation and treatment (Standard Management-SM).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There are many ways that use of a MSU might prove valuable in stroke patients, but we will&#xD;
      focus on acute ischemic stroke (AIS) and treatment with IV tissue plasminogen activator (tPA)&#xD;
      within 4.5 hours of symptom onset since that is the most evidence based effective emergency&#xD;
      treatment for the most prevalent stroke diagnosis. We hypothesize that the MSU pathway will&#xD;
      result in an overall shift towards earlier evaluation and treatment, particularly into the&#xD;
      first hour after symptom onset, leading to substantially better outcome. We also hypothesize&#xD;
      that as a result of improved clinical outcomes resulting from earlier treatment, the costs of&#xD;
      a MSU program will be offset by a reduction in the costs of long term stroke care and&#xD;
      increase in quality adjusted life years, thereby supporting more widespread use of this&#xD;
      technology. To make MSU deployment more practical, we will confirm that a Vascular&#xD;
      Neurologist (VN) on board the MSU can be replaced by a remote VN connected to the MSU by&#xD;
      telemedicine (TM) thereby reducing manpower requirements and costs.&#xD;
&#xD;
      The successful completion of this project will provide data on important outcomes and costs&#xD;
      associated with the use of MSU vs SM in the United States (U.S.) that will help determine the&#xD;
      value of integrating MSUs into the pre-hospital environment in this country. Successfully&#xD;
      addressing our three Specific Aims (time saved/ complications encountered, utility of TM, and&#xD;
      cost effectiveness) will provide critical information that will be needed to determine if and&#xD;
      how a subsequent more definitive study should be conducted. We anticipate that emanating from&#xD;
      this exploratory study would be a larger multicenter trial carried out in both urban and&#xD;
      rural U.S. pre-hospital environments, with treatment orchestrated via TM, and having&#xD;
      sufficient power to determine a difference in long term outcome and costs between patients&#xD;
      managed on the two pathways, following a study design that will be tested in this exploratory&#xD;
      trial. The present study, therefore, is the necessary first step in a process which may&#xD;
      dramatically modify the way that acute stroke patients are managed in the U.S.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">August 2014</start_date>
  <completion_date type="Anticipated">August 2023</completion_date>
  <primary_completion_date type="Actual">December 2021</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Alternating week assignment to groups. Entry criteria adjudicated by masked investigator. Primary outcome also by masked investigator.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Utility-weighted modified Rankin Scale (uw-mRS) from baseline to 90 days</measure>
    <time_frame>90 days (+/- 10 days) from date of enrollment</time_frame>
    <description>Comparing patients found eligible for tPA (based on a blinded review of the patient's chart, regardless of whether they were treated or not) on MSU weeks compared to SM weeks. With a sample size of 693 total tPA-eligible patients (446 MSU and 247 SM patients, assuming 10% lost to follow-up), the study will have 80% power with a 0.05 Type I error rate to detect a difference between groups of 0.09 in the mean uw-mRS using a two-sample t-test.At total of 693 tPA treated patients will allow 85% power to detect a 25 min decrease in time to treatment between the two groups using a one- sided alpha level of 0.05</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Agreement between on scene Vascular Neurologist vs. Remote (Telemedicine) Vascular Neurologist</measure>
    <time_frame>up to 4.5 hours from symptom onset</time_frame>
    <description>The agreement between a VN remotely assessing a suspected stroke patient via TM in the MSU and in-person assessment by a VN in the MSU will be assessed by using the Kappa statistic. We anticipate that the estimated sample size of 162 is needed to allow us 90 % power to detect 90% agreement between the in-person assessment and the TM.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cost Effectiveness (N.B. The BEST-MSU study including measurement of heatlhcare utilization is funded by PCORI. The cost-effectiveness measures are not covered by PCORI funding and will be reported separately)</measure>
    <time_frame>up to 1 year from date of enrollment</time_frame>
    <description>Cost Effectiveness as measured by average patient QALYs, post-stroke healthcare utilization, incremental fixed costs associated with MSU and the per-patient incremental fixed cost due the ambulance outfitting, CT, other equipment, telemedicine technology and staffing requirements.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>90 day Modified Rankin Score</measure>
    <time_frame>90 days (+/- 10 days) from date of enrollment</time_frame>
    <description>90 day Modified Rankin Score 0,1 vs 2-6, and ordinal shift analysis, of patients treated with tPA within 60 minutes of symptom onset according to published guidelines on either MSU or SM weeks, compared to similar patients treated 61-270 minutes after onset, adjusting for any imbalances in stroke severity (baseline NIHSS) between the groups at the time of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>90 day Modified Rankin Score</measure>
    <time_frame>90 days (+/- 10 days) from date of enrollment</time_frame>
    <description>90 day Modified Rankin Score 0,1 vs 2-6, and ordinal shift analysis, of all patients meeting published guidelines for treatment with tPA within 4.5 hours of symptom onset (whether eventually treated or not) on MSU weeks compared to patients meeting the same criteria (whether treated or not) on SM weeks, adjusting for any imbalances in stroke severity (baseline NIHSS) between the groups at the time of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from symptom onset to tPA treatment</measure>
    <time_frame>up to 4.5 hours from symptom onset</time_frame>
    <description>The time from LSN to tPA treatment on all patients treated within 4.5 hours of LSN on MSU weeks compared to similarly eligible patients on SM weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from symptom onset to Endovascular treatment</measure>
    <time_frame>up to 6 hours from symptom onset</time_frame>
    <description>The time from LSN and from ED arrival to start of endovascular procedure (intra-arterial thrombectomy-IAT) in patients who meet pre-specified criteria for IAT on MSU weeks compared to SM weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symptomatic intracranial hemorrhage and mortality</measure>
    <time_frame>up to hospital discharge</time_frame>
    <description>The incidence of symptomatic intracranial hemorrhage (sICH) and mortality in tPA treated patients on MSU weeks compared to SM weeks (Symptomatic intracranial hemorrhage defined as any intracranial blood accumulation associated with a clinical deterioration of 4 points of the NIHSS for which the hemorrhage has been identified as the dominating cause of the neurologic deterioration)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stroke mimics</measure>
    <time_frame>up to hospital discharge</time_frame>
    <description>The incidence of stroke mimics and transient ischemic attacks (TIAs) in tPA treated patients on MSU weeks compared to SM weeks.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1038</enrollment>
  <condition>Acute Ischemic Stroke</condition>
  <arm_group>
    <arm_group_label>Mobile Stroke Unit Management</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Acute ischemic stroke patients treated in the Mobile Stroke Unit</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard Management</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Acute ischemic stroke patients receiving standard management</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Mobile Stroke Unit Management</intervention_name>
    <description>Mobile Stroke Unit is a standard 12' Houston Fire Department ambulance equipped with point of care lab, CT scanner and staffed by a Vascular Neurologist, Registered Nurse with acute stroke and research experience, CT Technician and a Registered EMT-P. The MSU is dispatched in coordination with Houston, Bellaire and West University fire department/emergency medical services.</description>
    <arm_group_label>Mobile Stroke Unit Management</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Last seen normal within 4hr 30 min of symptom onset&#xD;
&#xD;
          -  History and physical/neurological examination consistent with acute stroke&#xD;
&#xD;
          -  No tPA exclusions per guidelines, prior to CT scan or baseline labs&#xD;
&#xD;
          -  Informed consent obtained from patient (if competent) or legal representative.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        -None&#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>James C Grotta, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Hermann</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Texas Health Science Center, Houston</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 10, 2014</study_first_submitted>
  <study_first_submitted_qc>July 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 15, 2014</study_first_posted>
  <last_update_submitted>March 16, 2023</last_update_submitted>
  <last_update_submitted_qc>March 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Memorial Hermann Health System</investigator_affiliation>
    <investigator_full_name>James Grotta, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>stroke</keyword>
  <keyword>tpa</keyword>
  <keyword>emergency medical service</keyword>
  <keyword>ems</keyword>
  <keyword>mobile</keyword>
  <keyword>ct scan</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>
  </condition_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>September 18, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/00/NCT02190500/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 1, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/00/NCT02190500/SAP_002.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT02190500
org study id: HSC 13-0322
nct id: NCT02190500
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The primary goal of this project is to carry out a trial comparing pre-hospital diagnosis and
      treatment of patients with stroke symptoms using a Mobile Stroke Unit (MSU) with subsequent
      transfer to a Comprehensive Stroke Center (CSC) Emergency Department (ED) for further
      management, to standard pre-hospital triage and transport by Emergency Medical Services (EMS)
      to a CSC ED for evaluation and treatment (Standard Management-SM).
There are many ways that use of a MSU might prove valuable in stroke patients, but we will
      focus on acute ischemic stroke (AIS) and treatment with IV tissue plasminogen activator (tPA)
      within 4.5 hours of symptom onset since that is the most evidence based effective emergency
      treatment for the most prevalent stroke diagnosis. We hypothesize that the MSU pathway will
      result in an overall shift towards earlier evaluation and treatment, particularly into the
      first hour after symptom onset, leading to substantially better outcome. We also hypothesize
      that as a result of improved clinical outcomes resulting from earlier treatment, the costs of
      a MSU program will be offset by a reduction in the costs of long term stroke care and
      increase in quality adjusted life years, thereby supporting more widespread use of this
      technology. To make MSU deployment more practical, we will confirm that a Vascular
      Neurologist (VN) on board the MSU can be replaced by a remote VN connected to the MSU by
      telemedicine (TM) thereby reducing manpower requirements and costs.

      The successful completion of this project will provide data on important outcomes and costs
      associated with the use of MSU vs SM in the United States (U.S.) that will help determine the
      value of integrating MSUs into the pre-hospital environment in this country. Successfully
      addressing our three Specific Aims (time saved/ complications encountered, utility of TM, and
      cost effectiveness) will provide critical information that will be needed to determine if and
      how a subsequent more definitive study should be conducted. We anticipate that emanating from
      this exploratory study would be a larger multicenter trial carried out in both urban and
      rural U.S. pre-hospital environments, with treatment orchestrated via TM, and having
      sufficient power to determine a difference in long term outcome and costs between patients
      managed on the two pathways, following a study design that will be tested in this exploratory
      trial. The present study, therefore, is the necessary first step in a process which may
      dramatically modify the way that acute stroke patients are managed in the U.S.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Alternating week assignment to groups. Entry criteria adjudicated by masked investigator. Primary outcome also by masked investigator.
measure: Utility-weighted modified Rankin Scale (uw-mRS) from baseline to 90 days
time frame: 90 days (+/- 10 days) from date of enrollment
description: Comparing patients found eligible for tPA (based on a blinded review of the patient's chart, regardless of whether they were treated or not) on MSU weeks compared to SM weeks. With a sample size of 693 total tPA-eligible patients (446 MSU and 247 SM patients, assuming 10% lost to follow-up), the study will have 80% power with a 0.05 Type I error rate to detect a difference between groups of 0.09 in the mean uw-mRS using a two-sample t-test.At total of 693 tPA treated patients will allow 85% power to detect a 25 min decrease in time to treatment between the two groups using a one- sided alpha level of 0.05
measure: Agreement between on scene Vascular Neurologist vs. Remote (Telemedicine) Vascular Neurologist
time frame: up to 4.5 hours from symptom onset
description: The agreement between a VN remotely assessing a suspected stroke patient via TM in the MSU and in-person assessment by a VN in the MSU will be assessed by using the Kappa statistic. We anticipate that the estimated sample size of 162 is needed to allow us 90 % power to detect 90% agreement between the in-person assessment and the TM.
measure: Cost Effectiveness (N.B. The BEST-MSU study including measurement of heatlhcare utilization is funded by PCORI. The cost-effectiveness measures are not covered by PCORI funding and will be reported separately)
time frame: up to 1 year from date of enrollment
description: Cost Effectiveness as measured by average patient QALYs, post-stroke healthcare utilization, incremental fixed costs associated with MSU and the per-patient incremental fixed cost due the ambulance outfitting, CT, other equipment, telemedicine technology and staffing requirements.
measure: 90 day Modified Rankin Score
time frame: 90 days (+/- 10 days) from date of enrollment
description: 90 day Modified Rankin Score 0,1 vs 2-6, and ordinal shift analysis, of patients treated with tPA within 60 minutes of symptom onset according to published guidelines on either MSU or SM weeks, compared to similar patients treated 61-270 minutes after onset, adjusting for any imbalances in stroke severity (baseline NIHSS) between the groups at the time of treatment.
measure: 90 day Modified Rankin Score
time frame: 90 days (+/- 10 days) from date of enrollment
description: 90 day Modified Rankin Score 0,1 vs 2-6, and ordinal shift analysis, of all patients meeting published guidelines for treatment with tPA within 4.5 hours of symptom onset (whether eventually treated or not) on MSU weeks compared to patients meeting the same criteria (whether treated or not) on SM weeks, adjusting for any imbalances in stroke severity (baseline NIHSS) between the groups at the time of treatment.
measure: Time from symptom onset to tPA treatment
time frame: up to 4.5 hours from symptom onset
description: The time from LSN to tPA treatment on all patients treated within 4.5 hours of LSN on MSU weeks compared to similarly eligible patients on SM weeks.
measure: Time from symptom onset to Endovascular treatment
time frame: up to 6 hours from symptom onset
description: The time from LSN and from ED arrival to start of endovascular procedure (intra-arterial thrombectomy-IAT) in patients who meet pre-specified criteria for IAT on MSU weeks compared to SM weeks.
measure: Symptomatic intracranial hemorrhage and mortality
time frame: up to hospital discharge
description: The incidence of symptomatic intracranial hemorrhage (sICH) and mortality in tPA treated patients on MSU weeks compared to SM weeks (Symptomatic intracranial hemorrhage defined as any intracranial blood accumulation associated with a clinical deterioration of 4 points of the NIHSS for which the hemorrhage has been identified as the dominating cause of the neurologic deterioration)
measure: Stroke mimics
time frame: up to hospital discharge
description: The incidence of stroke mimics and transient ischemic attacks (TIAs) in tPA treated patients on MSU weeks compared to SM weeks.
arm group label: Mobile Stroke Unit Management
arm group type: Active Comparator
description: Acute ischemic stroke patients treated in the Mobile Stroke Unit
arm group label: Standard Management
arm group type: No Intervention
description: Acute ischemic stroke patients receiving standard management
intervention type: Other
intervention name: Mobile Stroke Unit Management
description: Mobile Stroke Unit is a standard 12' Houston Fire Department ambulance equipped with point of care lab, CT scanner and staffed by a Vascular Neurologist, Registered Nurse with acute stroke and research experience, CT Technician and a Registered EMT-P. The MSU is dispatched in coordination with Houston, Bellaire and West University fire department/emergency medical services.
arm group label: Mobile Stroke Unit Management
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: James C Grotta, MD
role: Principal Investigator
affiliation: Memorial Hermann
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Memorial Hermann Health System
investigator full name: James Grotta, MD
investigator title: Principal Investigator
mesh term: Stroke
mesh term: Ischemic Stroke
provided document: 
provided document: 