xml: <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/NCT05963568</url>
    </required_header>
    <id_info>
      <org_study_id>22-37310</org_study_id>
      <nct_id>NCT05963568</nct_id>
    </id_info>
    <brief_title>Stroke Minimization Through Additive Anti-atherosclerotic Agents in Routine Treatment II Study (SMAART II)</brief_title>
    <official_title>Stroke Minimization Through Additive Anti-atherosclerotic Agents in Routine Treatment II Study (SMAART II)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Northern California Institute of Research and Education</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Northern California Institute of Research and Education</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>
    </oversight_info>
    <brief_summary>
      <textblock>
        The overall objective of the Stroke Minimization through Additive Anti-atherosclerotic Agents&#xD;
        in Routine Treatment II (SMAART-II) is to deploy a hybrid study design to firstly,&#xD;
        demonstrate the efficacy of a polypill (Polycap ®) containing fixed doses of&#xD;
        antihypertensives, a statin, and antiplatelet therapy taken as two capsules, once daily&#xD;
        orally in reducing composite vascular risk over 24 months vs. usual care among 500 recent&#xD;
        stroke patients encountered at 12 hospitals in Ghana. Secondly, SMAART II seeks to develop an&#xD;
        implementation strategy for routine integration and policy adoption of this polypill for&#xD;
        post-stroke cardiovascular risk reduction in an under-resourced system burdened by suboptimal&#xD;
        care and outcomes.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">May 2028</completion_date>
    <primary_completion_date type="Anticipated">May 2027</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>Prevention</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Composite vascular risk factor control</measure>
      <time_frame>12 and 24 months</time_frame>
      <description>Proportion of people who have 0, 1, 2 and 3 of the following: systolic BP &lt;140 mm Hg, LDL-cholesterol &lt;100mg/dl, antiplatelet adherence by pill count &gt;90%) at month 12 and month 24 (sustainment of effect)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Major adverse cardiovascular events (MACE)</measure>
      <time_frame>24 months</time_frame>
      <description>MACE to be assessed include recurrent stroke: fatal/severely disabling stroke or non-fatal stroke; coronary artery disease: acute STEMI/NSTEMI, sudden cardiac deaths. MACE will be confirmed by a blinded adjudication committee by reviewing available clinical notes supported by investigations for example CT scans, EKGs, troponin tests, death certificates or verbal autopsy if death occurs outside hospital.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in adherence to medical therapy</measure>
      <time_frame>Month 3, 6, 9, 12, 18 &amp; 24</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety and tolerability</measure>
      <time_frame>Up to 24 months</time_frame>
      <description>Side effects, adverse events, treatment withdrawal</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Health-related quality of life EuroQol-5D</measure>
      <time_frame>Up to 24 months</time_frame>
      <description>EuroQol-5D questionnaire (0-100 with 100 being the best)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Health-related quality of life Neuro-QoLTM</measure>
      <time_frame>Up to 24 months</time_frame>
      <description>NINDS Neuro-QoLTM (Quality of Life in Neurological Disorders) questionnaires (8-40 with 40 being the best)</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Organizational Capacity for Change Score</measure>
      <time_frame>Up to 30 months</time_frame>
      <description>Adoption i.e. Organizational Capacity for Change (OCC Scale Score comparison) with stratification by level of healthcare delivery. The measure is a 32-item multidimensional scale that evaluates an organization's capacity to upgrade or revise existing organizational competencies, while cultivating new competencies that enable the organization to survive and prosper. It comprises different aspects of leadership, employee behavior, and an organizational infrastructure supporting organizational change. Items are rated on a 5-point Likert scale. OCC has a Cronbach α of 0.87.</description>
    </other_outcome>
    <other_outcome>
      <measure>Mean Cost of Implementation</measure>
      <time_frame>Up to 30 months</time_frame>
      <description>Implementation Cost (mean monthly health expenses compared to standard of care)</description>
    </other_outcome>
    <other_outcome>
      <measure>Proportion who achieves systolic blood pressure &lt;140 mmHg</measure>
      <time_frame>Months 12 and 24</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Proportion who achieves blood pressure &lt;140/90 mmHg</measure>
      <time_frame>Months 12 and 24</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Proportion who achieves blood pressure &lt; 130 / 80 mmHg</measure>
      <time_frame>Months 12 and 24</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Proportion who achieves LDL-cholesterol &lt;100 mg/dl</measure>
      <time_frame>Months 12 and 24</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Proportion who achieves LDL-cholesterol &lt;70 mg/dl</measure>
      <time_frame>Months 12 and 24</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Proportion who achieves antiplatelet adherence of at least &gt;=80%</measure>
      <time_frame>Months 12 and 24</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Proportion who achieves antiplatelet adherence of at least &gt;= 90%</measure>
      <time_frame>Months 12 and 24</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Comparison of absolute and mean changes from baseline for blood pressure</measure>
      <time_frame>Up to 24 months</time_frame>
      <description>systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, measures of visit-to-visit variability in blood pressure</description>
    </other_outcome>
    <other_outcome>
      <measure>Comparison of absolute and mean changes from baseline for lipids</measure>
      <time_frame>Up to 24 months</time_frame>
      <description>Total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride</description>
    </other_outcome>
    <other_outcome>
      <measure>Proportion with recurrent strokes (fatal or non-fatal)</measure>
      <time_frame>Up to 24 months</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Proportion with coronary artery disease</measure>
      <time_frame>Up to 24 months</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Proportion with heart failure</measure>
      <time_frame>Up to 24 months</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Proportion with cardiovascular deaths</measure>
      <time_frame>Up to 24 months</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Proportion with all-cause mortality</measure>
      <time_frame>Up to 24 months</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Proportion with vascular cognitive impairment</measure>
      <time_frame>Months 12 and 24</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>Proportion with treatment-limiting adverse drug reactions or side effects</measure>
      <time_frame>Up to 24 months</time_frame>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">680</enrollment>
    <condition>Stroke</condition>
    <condition>Medication Adherence</condition>
    <arm_group>
      <arm_group_label>Intervention</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients allocated to the experimental arm will receive Two (2) (Polycap ®) taken orally once a day. A capsule of Polycap ® contains 100mg of Aspirin, 20mg of simvastatin, 12.5mg hydrochlorothiazide, 5mg of ramipril and 50mg of atenolol. Patients assigned to Polypill will have their antihypertensive agents, lipid modifiers and anti-thrombotic agents withdrawn &amp; replaced with the Polypill if they are already receiving such treatments before enrollment.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control arm</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Patients allocated to the usual care arm will receive standard of care therapies for secondary prevention with drugs and doses left at the discretion of the treating physicians. Since our focus is to isolate the effect of the polypill strategy itself &amp; create equipoise, at study inception providers for patients in both study arms will receive a brief one-time (Skype-based) training &amp; a one time email synopsis on guideline recommended biomarker targets after stroke.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Polycap</intervention_name>
      <description>Patients allocated to the experimental arm will receive Two (2) (Polycap ®) taken orally once a day. A capsule of Polycap ® contains 100mg of Aspirin, 20mg of simvastatin, 12.5mg hydrochlorothiazide, 5mg of ramipril and 50mg of atenolol. Patients assigned to Polypill will have their antihypertensive agents, lipid modifiers and anti-thrombotic agents withdrawn and replaced with the Polypill if they are already receiving such treatments before enrollment.</description>
      <arm_group_label>Intervention</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Above the age of 18 years; male or female&#xD;
  &#xD;
            -  Ischemic stroke diagnosis no greater than two months before enrollment. Ischemic&#xD;
               strokes including� lacunar, large-vessel atherosclerotic, cardio-embolic subtypes are&#xD;
               eligible&#xD;
  &#xD;
            -  Subjects with stroke may present with at least one of the following additional&#xD;
               conditions:&#xD;
  &#xD;
          Documented diabetes mellitus or previous treatment with oral hypoglycemic or insulin;&#xD;
          documented hypertension &gt;140/90mmHg or previous treatment with antihypertensive&#xD;
          medications; Mild to moderate renal dysfunction (eGFR 60-30ml/min/1.73m2); Prior myocardial&#xD;
          infarction&#xD;
  &#xD;
            -  Legally competent to sign informed consent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Unable to sign informed consent&#xD;
  &#xD;
            -  Contraindications to any of the components of the polypill&#xD;
  &#xD;
            -  Hemorrhagic stroke&#xD;
  &#xD;
            -  Severe cognitive impairment/dementia or severe global disability limiting the capacity&#xD;
               of self-care&#xD;
  &#xD;
            -  Severe congestive cardiac failure (NYHA III-IV)&#xD;
  &#xD;
            -  Severe renal disease, eGFR &lt;30ml/min/1.73m2), renal dialysis; awaiting renal&#xD;
               transplant or transplant recipient&#xD;
  &#xD;
            -  Cancer diagnosis or treatment in past 2 years&#xD;
  &#xD;
            -  Need for oral anticoagulation at the time of randomization or planned in the future&#xD;
               months;&#xD;
  &#xD;
            -  Significant arrhythmias (including unresolved ventricular arrhythmias or atrial&#xD;
               fibrillation)&#xD;
  &#xD;
            -  Nursing/pregnant mothers&#xD;
  &#xD;
            -  Do not agree to the filing, forwarding and use of his/her pseudonymized data.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>100 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Bruce Ovbiagele, MD</last_name>
      <phone>415-750-2047</phone>
      <email>bruce.ovbiagele@va.gov</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Raelle Tagge, MPH</last_name>
      <email>raelle.tagge@ncire.org</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Kwame Nkrumah Institute of Science &amp; Technology</name>
        <address>
          <city>Kumasi</city>
          <country>Ghana</country>
        </address>
      </facility>
      <contact>
        <last_name>Fred Sarfo, MD</last_name>
        <email>stephensarfo78@gmail.com</email>
      </contact>
    </location>
    <location_countries>
      <country>Ghana</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 11, 2022</study_first_submitted>
    <study_first_submitted_qc>July 19, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 27, 2023</study_first_posted>
    <last_update_submitted>September 12, 2023</last_update_submitted>
    <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 14, 2023</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>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05963568
  org study id: 22-37310
  nct id: NCT05963568
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The overall objective of the Stroke Minimization through Additive Anti-atherosclerotic Agents
        in Routine Treatment II (SMAART-II) is to deploy a hybrid study design to firstly,
        demonstrate the efficacy of a polypill (Polycap ®) containing fixed doses of
        antihypertensives, a statin, and antiplatelet therapy taken as two capsules, once daily
        orally in reducing composite vascular risk over 24 months vs. usual care among 500 recent
        stroke patients encountered at 12 hospitals in Ghana. Secondly, SMAART II seeks to develop an
        implementation strategy for routine integration and policy adoption of this polypill for
        post-stroke cardiovascular risk reduction in an under-resourced system burdened by suboptimal
        care and outcomes.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Prevention
  masking: Single (Outcomes Assessor)
  measure: Composite vascular risk factor control
  time frame: 12 and 24 months
  description: Proportion of people who have 0, 1, 2 and 3 of the following: systolic BP <140 mm Hg, LDL-cholesterol <100mg/dl, antiplatelet adherence by pill count >90%) at month 12 and month 24 (sustainment of effect)
  measure: Major adverse cardiovascular events (MACE)
  time frame: 24 months
  description: MACE to be assessed include recurrent stroke: fatal/severely disabling stroke or non-fatal stroke; coronary artery disease: acute STEMI/NSTEMI, sudden cardiac deaths. MACE will be confirmed by a blinded adjudication committee by reviewing available clinical notes supported by investigations for example CT scans, EKGs, troponin tests, death certificates or verbal autopsy if death occurs outside hospital.
  measure: Change in adherence to medical therapy
  time frame: Month 3, 6, 9, 12, 18 & 24
  measure: Safety and tolerability
  time frame: Up to 24 months
  description: Side effects, adverse events, treatment withdrawal
  measure: Health-related quality of life EuroQol-5D
  time frame: Up to 24 months
  description: EuroQol-5D questionnaire (0-100 with 100 being the best)
  measure: Health-related quality of life Neuro-QoLTM
  time frame: Up to 24 months
  description: NINDS Neuro-QoLTM (Quality of Life in Neurological Disorders) questionnaires (8-40 with 40 being the best)
  measure: Organizational Capacity for Change Score
  time frame: Up to 30 months
  description: Adoption i.e. Organizational Capacity for Change (OCC Scale Score comparison) with stratification by level of healthcare delivery. The measure is a 32-item multidimensional scale that evaluates an organization's capacity to upgrade or revise existing organizational competencies, while cultivating new competencies that enable the organization to survive and prosper. It comprises different aspects of leadership, employee behavior, and an organizational infrastructure supporting organizational change. Items are rated on a 5-point Likert scale. OCC has a Cronbach α of 0.87.
  measure: Mean Cost of Implementation
  time frame: Up to 30 months
  description: Implementation Cost (mean monthly health expenses compared to standard of care)
  measure: Proportion who achieves systolic blood pressure <140 mmHg
  time frame: Months 12 and 24
  measure: Proportion who achieves blood pressure <140/90 mmHg
  time frame: Months 12 and 24
  measure: Proportion who achieves blood pressure < 130 / 80 mmHg
  time frame: Months 12 and 24
  measure: Proportion who achieves LDL-cholesterol <100 mg/dl
  time frame: Months 12 and 24
  measure: Proportion who achieves LDL-cholesterol <70 mg/dl
  time frame: Months 12 and 24
  measure: Proportion who achieves antiplatelet adherence of at least >=80%
  time frame: Months 12 and 24
  measure: Proportion who achieves antiplatelet adherence of at least >= 90%
  time frame: Months 12 and 24
  measure: Comparison of absolute and mean changes from baseline for blood pressure
  time frame: Up to 24 months
  description: systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, measures of visit-to-visit variability in blood pressure
  measure: Comparison of absolute and mean changes from baseline for lipids
  time frame: Up to 24 months
  description: Total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride
  measure: Proportion with recurrent strokes (fatal or non-fatal)
  time frame: Up to 24 months
  measure: Proportion with coronary artery disease
  time frame: Up to 24 months
  measure: Proportion with heart failure
  time frame: Up to 24 months
  measure: Proportion with cardiovascular deaths
  time frame: Up to 24 months
  measure: Proportion with all-cause mortality
  time frame: Up to 24 months
  measure: Proportion with vascular cognitive impairment
  time frame: Months 12 and 24
  measure: Proportion with treatment-limiting adverse drug reactions or side effects
  time frame: Up to 24 months
  arm group label: Intervention
  arm group type: Experimental
  description: Patients allocated to the experimental arm will receive Two (2) (Polycap ®) taken orally once a day. A capsule of Polycap ® contains 100mg of Aspirin, 20mg of simvastatin, 12.5mg hydrochlorothiazide, 5mg of ramipril and 50mg of atenolol. Patients assigned to Polypill will have their antihypertensive agents, lipid modifiers and anti-thrombotic agents withdrawn & replaced with the Polypill if they are already receiving such treatments before enrollment.
  arm group label: Control arm
  arm group type: No Intervention
  description: Patients allocated to the usual care arm will receive standard of care therapies for secondary prevention with drugs and doses left at the discretion of the treating physicians. Since our focus is to isolate the effect of the polypill strategy itself & create equipoise, at study inception providers for patients in both study arms will receive a brief one-time (Skype-based) training & a one time email synopsis on guideline recommended biomarker targets after stroke.
  intervention type: Drug
  intervention name: Polycap
  description: Patients allocated to the experimental arm will receive Two (2) (Polycap ®) taken orally once a day. A capsule of Polycap ® contains 100mg of Aspirin, 20mg of simvastatin, 12.5mg hydrochlorothiazide, 5mg of ramipril and 50mg of atenolol. Patients assigned to Polypill will have their antihypertensive agents, lipid modifiers and anti-thrombotic agents withdrawn and replaced with the Polypill if they are already receiving such treatments before enrollment.
  arm group label: Intervention
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 100 Years
  healthy volunteers: No
  last name: Bruce Ovbiagele, MD
  phone: 415-750-2047
  email: bruce.ovbiagele@va.gov
  last name: Raelle Tagge, MPH
  email: raelle.tagge@ncire.org
  facility: 
  contact: 
  country: Ghana
  responsible party type: Sponsor
  mesh term: Stroke