<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/NCT03024476</url>
  </required_header>
  <id_info>
    <org_study_id>B-1604/343</org_study_id>
    <nct_id>NCT03024476</nct_id>
  </id_info>
  <brief_title>Optimization of Blood Pressure Management After Acute Ischemic Stroke and Its Prognostic Significance</brief_title>
  <official_title>Optimization of Blood Pressure Management After Acute Ischemic Stroke and Its Prognostic Significance: Prospective, Randomized, Open, Blinded Outcome Evaluation, and Feasibility Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Seoul National University Bundang Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Daiichi Sankyo Korea Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Seoul National University Bundang Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      BOSS-Trial I is a phase 2 clinical trial with the following objectives;&#xD;
&#xD;
        1. to prove the feasibility of a Bluetooth-equipped sphygmomanometer system in real-world&#xD;
           clinical practice and wireless connection to the main server;&#xD;
&#xD;
        2. to prove the feasibility of the BP management strategy, including the pre-specified BP&#xD;
           range, BP management algorithm, and behavioral; and&#xD;
&#xD;
        3. to gather information for the phase 3 trial including BP variability indices and their&#xD;
           potentials as a treatment guidance.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      -  Elevated blood pressure is an established risk factor for recurrent stroke and vascular&#xD;
           events in ischemic stroke survivors, but&#xD;
&#xD;
        -  Current guideline (JNC VIII) has omitted or only partially covered a number of practical&#xD;
           and important issues as follow;&#xD;
&#xD;
             -  When and how we measure blood pressure?&#xD;
&#xD;
             -  Is it justifiable to apply the same blood pressure threshold for office BP and home&#xD;
                BP?&#xD;
&#xD;
             -  Should stroke survivors be treated by the same BP goal for non-stroke subjects?&#xD;
&#xD;
             -  Is it justifiable to apply the universal BP threshold for different mechanisms of&#xD;
                ischemic stroke?&#xD;
&#xD;
             -  Is it really about only blood pressure or might it really be &quot;beyond blood&#xD;
                pressure?&quot;&#xD;
&#xD;
        -  Lifestyle modification should accompany all the pharmacological intervention but is&#xD;
           usually in adequate to initiate behavioral changes.&#xD;
&#xD;
        -  Frequent BP measurement at home will provide more detailed and reliable information than&#xD;
           occasional office BP's.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2016</start_date>
  <completion_date type="Actual">December 7, 2017</completion_date>
  <primary_completion_date type="Actual">December 7, 2017</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recruitment time to prespecified number of subjects</measure>
    <time_frame>At 3 months after randomization</time_frame>
    <description>Difference in days between recruitment of the first subject and last subject</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Retention of included participants</measure>
    <time_frame>At 3 months after randomization</time_frame>
    <description>Ratio of completed subject over randomized subjects in each group</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Frequencies of calls for breakthrough visit</measure>
    <time_frame>At 3 months after randomization</time_frame>
    <description>Mean and standard deviation of breakthrough visits per each patient in the intensive management group</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rate of patients who responded to the calls for breakthrough visit</measure>
    <time_frame>At 3 months after randomization</time_frame>
    <description>ratio of subjects response over the breakthrough visit calls</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Control of blood pressure</measure>
    <time_frame>At 3 months after randomization</time_frame>
    <description>ratio of subjects with well-controlled BP in each group</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency of out-of-range measurement</measure>
    <time_frame>At 3 months after randomization</time_frame>
    <description>Frequency of BP measurements out of the desirable BP range in a week</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weighted hit score of BP</measure>
    <time_frame>At 3 months after randomization</time_frame>
    <description>When two consecutive hits crossed over or below the margin of desirable BP, give 2x weight. Final score will be generated by dividing by total number of measurements</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vascular events</measure>
    <time_frame>At 3 months after randomization</time_frame>
    <description>Recurrent vascular events including recurrent stroke, myocardial infarction or vascular death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hypotensive events</measure>
    <time_frame>Until 3 months after randomization</time_frame>
    <description>Complaint of dizzy spells, falls or low-BP related events by patients</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">67</enrollment>
  <condition>Ischemic Stroke</condition>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Intensive management arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Description:&#xD;
Interventions in the intensive management arm consist of 1) behavioral intensification and 2) pharmacological intensification based on olmesartan&#xD;
Participants will be given a wireless Bluetooth-equipped sphygmomanometer system, which is connected to the main server through the participants' own smartphone. Every blood pressure and heart rate measured will be encrypted and stored in the main server (Identical for both intervention and control groups).&#xD;
Regarding behavioral intensification, an automated texting and call for breakthrough visit will be sent from the main server to encourage regular measurements of BP and maintain a desirable goad of BP.&#xD;
Regarding pharmacological intensification, a specific algorithm for BP-lowering medication prescription will be provided to the responsible physicians by the steering committee.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Description:&#xD;
Other than a bluetooth-equipped sphygmomanometer, standard managements abiding by the most current guideline will be provided from the responsible physicians.&#xD;
Participants will be given a Bluetooth-equipped sphygmomanometer, which is connected to the main server through the participants' own smartphone. Every blood pressure and heart rate measured will be encrypted and stored in the main server (Identical for both intervention and control groups).</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Behavioral intensification</intervention_name>
    <description>Suggested algorithm for behavioral intensification:&#xD;
If frequency of BP measurement ≤5 in a week, send a texting message&#xD;
If frequency of BP measurement ≤3 in a week, make a telephone contact by research nurse&#xD;
Target range of home-systolic blood pressure: 110 - 135&#xD;
If rate of outlier exceeds 50% in a week (based on ≥5 measurements in a week), make a telephone contact by research nurse (applied at least 2 weeks after randomization). A call for breakthrough visit may be issued when clinically required (decided by the institutional investigator)&#xD;
If frequency of BP measurement ≥ 10 in a week and frequency of outlier = 0 in a week, send a texting message to encourage and compliment on excellent BP management</description>
    <arm_group_label>Intensive management arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pharmacological intensification based on olmesartan</intervention_name>
    <description>Study drug will be provided from the roll-in period.&#xD;
Step I:&#xD;
Use olmesartan 20 mg only if mean systolic blood pressure ≤150 mm Hg during the immediate past 2 days&#xD;
Use olmesartan 40 mg if mean systolic blood pressure &gt;150 during the immediate past 2 days&#xD;
Step II: olmesartan 20 mg or 40 mg + amlodipine 5 mg&#xD;
Step III: olmesartan 20 mg or 40 mg + amlodipine 10 mg&#xD;
Step IV: olmesartan 20 mg or 40 mg + amlodipine 10 mg + hydrochlorothiazide 12.5 mg&#xD;
If blood pressure profile showed high degree variability to evoke clinical concern, consider discontinuation of hydrochlorothiazide or reduction of olmesartan dose.&#xD;
Use of beta-blockers is permitted if clinically indicated.&#xD;
At each clinic visit regardless of regular or breakthrough visit, follow the pharmacological intensification rule.</description>
    <arm_group_label>Intensive management arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Bluetooth-equipped sphygmomanometer</intervention_name>
    <description>Participants will be given a wireless Bluetooth-equipped sphygmomanometer system, which is connected to the main server through the participants' own smartphone. (Identical for both intervention and control groups)&#xD;
Every blood pressure and heart rate measured will be encrypted and stored in the main server. (Identical for both intervention and control groups)</description>
    <arm_group_label>Control arm</arm_group_label>
    <arm_group_label>Intensive management arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ischemic stroke survivors within 7 days after onset&#xD;
&#xD;
          -  ≥19 year-old male or female&#xD;
&#xD;
          -  Medically and neurologically stabilized enough to take BP-lowering medication&#xD;
&#xD;
          -  Mean systolic blood pressure ≥135 mm Hg during two days between at least 24 hours&#xD;
             after onset and randomization (whether BP-lowering medication was prescribed or not)&#xD;
&#xD;
          -  Capable of taking oral medication&#xD;
&#xD;
          -  Capable of operating a wireless Bluetooth-equipped sphygmomanometer system and being&#xD;
             expected to follow required procedures of the clinical trial&#xD;
&#xD;
          -  Patients who provided written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant, puerperium ≤30 days or on breastfeeding&#xD;
&#xD;
          -  enrolled in other interventional clinical trial&#xD;
&#xD;
          -  Being transferred to rehabilitation center or institutionalized&#xD;
&#xD;
          -  Being expected to have cerebral artery interventions within 3 months after&#xD;
             randomization&#xD;
&#xD;
          -  Known allergic reactions to olmesartan, amlodipine or hydrochlorothiazide&#xD;
&#xD;
          -  Known severe hepatic disease&#xD;
&#xD;
          -  Advanced kidney dysfunction requiring dialysis&#xD;
&#xD;
          -  Being unlikely, in the opinion of the investigator, to comply with the clinical trial&#xD;
             protocol or being unsuitable for any other reason.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hee-Joon Bae, MD.PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Seoul National University Bundang Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Seoul National University Bundang Hospital</name>
      <address>
        <city>Seongnam</city>
        <state>Gyeonggi</state>
        <zip>13520</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nowon Eulji Medical Center, Eulji University</name>
      <address>
        <city>Seoul</city>
        <zip>01830</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>02053</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>January 3, 2017</study_first_submitted>
  <study_first_submitted_qc>January 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <last_update_submitted>April 4, 2018</last_update_submitted>
  <last_update_submitted_qc>April 4, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Seoul National University Bundang Hospital</investigator_affiliation>
    <investigator_full_name>Hee-Joon Bae</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>behavioral intervention</keyword>
  <keyword>prespecified medication algorithm</keyword>
  <keyword>bluetooth-equipped sphygmomanometer</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>Olmesartan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>May 3, 2022</submitted>
    <returned>February 2, 2023</returned>
  </pending_results>
  <!-- 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/NCT03024476
org study id: B-1604/343
nct id: NCT03024476
lead sponsor: 
collaborator: 
has dmc: Yes
BOSS-Trial I is a phase 2 clinical trial with the following objectives;

        1. to prove the feasibility of a Bluetooth-equipped sphygmomanometer system in real-world
           clinical practice and wireless connection to the main server;

        2. to prove the feasibility of the BP management strategy, including the pre-specified BP
           range, BP management algorithm, and behavioral; and

        3. to gather information for the phase 3 trial including BP variability indices and their
           potentials as a treatment guidance.
-  Elevated blood pressure is an established risk factor for recurrent stroke and vascular
           events in ischemic stroke survivors, but

        -  Current guideline (JNC VIII) has omitted or only partially covered a number of practical
           and important issues as follow;

             -  When and how we measure blood pressure?

             -  Is it justifiable to apply the same blood pressure threshold for office BP and home
                BP?

             -  Should stroke survivors be treated by the same BP goal for non-stroke subjects?

             -  Is it justifiable to apply the universal BP threshold for different mechanisms of
                ischemic stroke?

             -  Is it really about only blood pressure or might it really be "beyond blood
                pressure?"

        -  Lifestyle modification should accompany all the pharmacological intervention but is
           usually in adequate to initiate behavioral changes.

        -  Frequent BP measurement at home will provide more detailed and reliable information than
           occasional office BP's.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Recruitment time to prespecified number of subjects
time frame: At 3 months after randomization
description: Difference in days between recruitment of the first subject and last subject
measure: Retention of included participants
time frame: At 3 months after randomization
description: Ratio of completed subject over randomized subjects in each group
measure: Frequencies of calls for breakthrough visit
time frame: At 3 months after randomization
description: Mean and standard deviation of breakthrough visits per each patient in the intensive management group
measure: Rate of patients who responded to the calls for breakthrough visit
time frame: At 3 months after randomization
description: ratio of subjects response over the breakthrough visit calls
measure: Control of blood pressure
time frame: At 3 months after randomization
description: ratio of subjects with well-controlled BP in each group
measure: Frequency of out-of-range measurement
time frame: At 3 months after randomization
description: Frequency of BP measurements out of the desirable BP range in a week
measure: Weighted hit score of BP
time frame: At 3 months after randomization
description: When two consecutive hits crossed over or below the margin of desirable BP, give 2x weight. Final score will be generated by dividing by total number of measurements
measure: Vascular events
time frame: At 3 months after randomization
description: Recurrent vascular events including recurrent stroke, myocardial infarction or vascular death
measure: Hypotensive events
time frame: Until 3 months after randomization
description: Complaint of dizzy spells, falls or low-BP related events by patients
arm group label: Intensive management arm
arm group type: Experimental
description: Description:
Interventions in the intensive management arm consist of 1) behavioral intensification and 2) pharmacological intensification based on olmesartan
Participants will be given a wireless Bluetooth-equipped sphygmomanometer system, which is connected to the main server through the participants' own smartphone. Every blood pressure and heart rate measured will be encrypted and stored in the main server (Identical for both intervention and control groups).
Regarding behavioral intensification, an automated texting and call for breakthrough visit will be sent from the main server to encourage regular measurements of BP and maintain a desirable goad of BP.
Regarding pharmacological intensification, a specific algorithm for BP-lowering medication prescription will be provided to the responsible physicians by the steering committee.
arm group label: Control arm
arm group type: Active Comparator
description: Description:
Other than a bluetooth-equipped sphygmomanometer, standard managements abiding by the most current guideline will be provided from the responsible physicians.
Participants will be given a Bluetooth-equipped sphygmomanometer, which is connected to the main server through the participants' own smartphone. Every blood pressure and heart rate measured will be encrypted and stored in the main server (Identical for both intervention and control groups).
intervention type: Behavioral
intervention name: Behavioral intensification
description: Suggested algorithm for behavioral intensification:
If frequency of BP measurement ≤5 in a week, send a texting message
If frequency of BP measurement ≤3 in a week, make a telephone contact by research nurse
Target range of home-systolic blood pressure: 110 - 135
If rate of outlier exceeds 50% in a week (based on ≥5 measurements in a week), make a telephone contact by research nurse (applied at least 2 weeks after randomization). A call for breakthrough visit may be issued when clinically required (decided by the institutional investigator)
If frequency of BP measurement ≥ 10 in a week and frequency of outlier = 0 in a week, send a texting message to encourage and compliment on excellent BP management
arm group label: Intensive management arm
intervention type: Drug
intervention name: Pharmacological intensification based on olmesartan
description: Study drug will be provided from the roll-in period.
Step I:
Use olmesartan 20 mg only if mean systolic blood pressure ≤150 mm Hg during the immediate past 2 days
Use olmesartan 40 mg if mean systolic blood pressure >150 during the immediate past 2 days
Step II: olmesartan 20 mg or 40 mg + amlodipine 5 mg
Step III: olmesartan 20 mg or 40 mg + amlodipine 10 mg
Step IV: olmesartan 20 mg or 40 mg + amlodipine 10 mg + hydrochlorothiazide 12.5 mg
If blood pressure profile showed high degree variability to evoke clinical concern, consider discontinuation of hydrochlorothiazide or reduction of olmesartan dose.
Use of beta-blockers is permitted if clinically indicated.
At each clinic visit regardless of regular or breakthrough visit, follow the pharmacological intensification rule.
arm group label: Intensive management arm
intervention type: Device
intervention name: Bluetooth-equipped sphygmomanometer
description: Participants will be given a wireless Bluetooth-equipped sphygmomanometer system, which is connected to the main server through the participants' own smartphone. (Identical for both intervention and control groups)
Every blood pressure and heart rate measured will be encrypted and stored in the main server. (Identical for both intervention and control groups)
arm group label: Control arm
arm group label: Intensive management arm
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Hee-Joon Bae, MD.PhD
role: Principal Investigator
affiliation: Seoul National University Bundang Hospital
facility: 
facility: 
facility: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Seoul National University Bundang Hospital
investigator full name: Hee-Joon Bae
investigator title: Professor
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Cerebral Infarction
mesh term: Ischemia
mesh term: Olmesartan
sharing ipd: Undecided
submitted: May 3, 2022
returned: February 2, 2023