<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/NCT03808311</url>
  </required_header>
  <id_info>
    <org_study_id>Ruijin-2018-138-2</org_study_id>
    <nct_id>NCT03808311</nct_id>
  </id_info>
  <brief_title>Blood Pressure Control Target in Diabetes</brief_title>
  <acronym>BPROAD</acronym>
  <official_title>Blood Pressure Control Target in Diabetes (BPROAD): A Multicenter, Open-label, Parallel-group, Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Jiao Tong University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Jiao Tong University School of Medicine</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicenter, open-label, parallel-group, randomized controlled trial that will be&#xD;
      conducted across mainland China. This trial will test the primary hypothesis of whether an&#xD;
      intensive treatment strategy (a systolic blood pressure target of &lt;120 mmHg) is more&#xD;
      effective than a standard treatment strategy (a systolic blood pressure target of &lt;140 mmHg)&#xD;
      in reducing the risk of major cardiovascular disease (non-fatal stroke, non-fatal myocardial&#xD;
      infarction, treated or hospitalized heart failure, and cardiovascular deaths) over a&#xD;
      follow-up period of up to 5 years among patients with a history of diabetes and elevated&#xD;
      systolic blood pressure. The secondary hypotheses are to compare the intensive blood pressure&#xD;
      treatment strategy with the standard treatment strategy on dementia and cognitive function,&#xD;
      individual components of the primary hypothesis, all-cause mortality, kidney outcomes,&#xD;
      quality of life, and injurious falls, et al.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The trial will recruit 12,702 patients from approximately 200 hospitals within the China&#xD;
      Diabetes Clinical Research Network. Eligible criteria include men and women aged ≥50 years;&#xD;
      type 2 diabetes mellitus; elevated systolic blood pressure; and a history of clinical&#xD;
      cardiovascular disease or increased risk for cardiovascular disease. Main exclusion criteria&#xD;
      include known secondary cause of hypertension, symptomatic heart failure, end-stage renal&#xD;
      disease, and other serious illness. The proposed trial has 90% statistical power to detect a&#xD;
      20% reduction (hazard ratio of 0.80) in major cardiovascular disease between intensive and&#xD;
      standard treatment groups at a 2-sided significance level of 0.05.&#xD;
&#xD;
      To achieve the proposed study objectives, the following specific aims will be accomplished:&#xD;
&#xD;
        1. Recruit 12,702 study participants who meet the eligibility criteria and randomly assign&#xD;
           6,351 to the intensive blood pressure treatment and 6,351 to the standard blood pressure&#xD;
           treatment groups;&#xD;
&#xD;
        2. Achieve and maintain two-level targets of systolic blood pressure (&lt;120 mmHg vs. &lt;140&#xD;
           mmHg) with a mean systolic blood pressure difference of ≥15 mmHg;&#xD;
&#xD;
        3. Employ a study-wide strategy to encourage standard of care for all participants for the&#xD;
           treatment of type 2 diabetes and dyslipidemia other than blood pressure;&#xD;
&#xD;
        4. Obtain clinical data on study outcomes for up to 60 months of follow-up among all trial&#xD;
           participants;&#xD;
&#xD;
        5. Perform strict quality control procedures for intervention and data collection;&#xD;
&#xD;
        6. Conduct data analysis according to the intention-to-treat principle; and&#xD;
&#xD;
        7. Disseminate the study findings to influence clinical practice and clinical guidelines.&#xD;
&#xD;
      Findings from this trial will provide evidence as to whether intensive blood pressure&#xD;
      management to achieve a systolic blood pressure target of &lt;120 mmHg has additional benefits&#xD;
      over standard management of systolic blood pressure &lt;140 mmHg. These findings will help in&#xD;
      the development of clinical guidelines for blood pressure management among patients with type&#xD;
      2 diabetes and will have important clinical impact.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 24, 2019</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">February 2024</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Major cardiovascular events</measure>
    <time_frame>5 years</time_frame>
    <description>Time to the first occurrence of any of the following: non-fatal stroke, non-fatal myocardial infarction, hospitalized or treated heart failure, or cardiovascular deaths</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>A composite of the primary outcome and all-cause mortality</measure>
    <time_frame>5 years</time_frame>
    <description>Time to the first occurrence of any of the following: non-fatal stroke, non-fatal MI, hospitalized or treated heart failure, or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Macrovascular outcome</measure>
    <time_frame>5 years</time_frame>
    <description>Time to the first occurrence of any of the following: non-fatal stroke, non-fatal MI, hospitalized or treated heart failure, cardiovascular deaths, treated or hospitalized unstable angina, or any cardiovascular revascularization procedures</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major coronary artery diseases</measure>
    <time_frame>5 years</time_frame>
    <description>Time to the first occurrence of any of the following: non-fatal MI, treated or hospitalized unstable angina, revascularization of coronary arteries, or deaths due to coronary artery diseases</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total stroke</measure>
    <time_frame>5 years</time_frame>
    <description>Fatal and non-fatal stroke</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart failure</measure>
    <time_frame>5 years</time_frame>
    <description>Hospitalized or treated heart failure, or heart failure death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiovascular death</measure>
    <time_frame>5 years</time_frame>
    <description>Deaths due to cardiovascular causes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total mortality</measure>
    <time_frame>5 years</time_frame>
    <description>Deaths due to any causes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive function</measure>
    <time_frame>5 years</time_frame>
    <description>Incidence of all-cause dementia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health related quality of life</measure>
    <time_frame>5 years</time_frame>
    <description>Evaluated with HQoL scales such as Short Form 12 Health Survey Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kidney outcomes</measure>
    <time_frame>5 years</time_frame>
    <description>Progression of CKD, development of CKD, and incident albuminuria</description>
  </secondary_outcome>
  <other_outcome>
    <measure>All cardiovascular revascularization procedures</measure>
    <time_frame>5 years</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Treated or hospitalized unstable angina</measure>
    <time_frame>5 years</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Retinopathy</measure>
    <time_frame>5 years</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Transient ischemic attack (TIA)</measure>
    <time_frame>5 years</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Left ventricular hypertrophy (LVH)</measure>
    <time_frame>5 years</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Atrial fibrillation or flutter</measure>
    <time_frame>5 years</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>All cancers</measure>
    <time_frame>5 years</time_frame>
    <description>Time to the first occurrence of any types of cancer</description>
  </other_outcome>
  <other_outcome>
    <measure>Cost-effectiveness</measure>
    <time_frame>5 years</time_frame>
    <description>The incremental cost per quality adjusted life year (QALY) gained. QALYs will be measured by the EuroQol-5 Dimensions (EQ-5D) questionnaire.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12821</enrollment>
  <condition>Blood Pressure Control Target in Diabetes</condition>
  <arm_group>
    <arm_group_label>Intensive BP treatment arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in the intensive BP treatment arm will be treated to a systolic BP target of &lt;120 mmHg.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard BP treatment arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants in the standard BP treatment arm will be treated to a systolic BP target of &lt;140 mmHg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Treatment strategy regarding different systolic BP goals</intervention_name>
    <description>The trial will test a treatment strategy question regarding different systolic BP goals and not test specific medications. Therefore, the BP treatment protocol is flexible in terms of the choice and doses of anti-hypertensive medications as long as systolic BP levels are within targets (&lt;120 mmHg in the intensive arm and &lt;140 mmHg in the standard arm).</description>
    <arm_group_label>Intensive BP treatment arm</arm_group_label>
    <arm_group_label>Standard BP treatment arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Men and women aged ≥50 years;&#xD;
&#xD;
          2. Diabetes defined as:&#xD;
&#xD;
               -  A self-reported previous diagnosis by health care professionals and taking&#xD;
                  anti-diabetic medications;&#xD;
&#xD;
               -  Fasting plasma glucose level of ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no&#xD;
                  caloric intake for at least 8 hours;&#xD;
&#xD;
               -  2-hour plasma glucose level of ≥200 mg/dL (11.1 mmol/L) during an oral glucose&#xD;
                  tolerance test. The test should be performed using a glucose load containing the&#xD;
                  equivalent of 75 g anhydrous glucose dissolved in water; or&#xD;
&#xD;
               -  HbA1c concentration of ≥6.5% (48 mmol/mol);&#xD;
&#xD;
          3. Systolic blood pressure&#xD;
&#xD;
             -≥140 mmHg on 0 medication;&#xD;
&#xD;
               -  130-180 mmHg on 1 medication;&#xD;
&#xD;
               -  130-170 mmHg on up to 2 medications;&#xD;
&#xD;
               -  130-160 mmHg on up to 3 medications; or&#xD;
&#xD;
               -  130-150 mmHg on up to 4 medications;&#xD;
&#xD;
          4. Increased risk of cardiovascular disease (one or more of the following):&#xD;
&#xD;
               -  Previous history of clinical CVD (≥ 3 months)&#xD;
&#xD;
               -  Subclinical CVD within 3 years&#xD;
&#xD;
               -  2 or more CVD risk factors&#xD;
&#xD;
               -  Estimated glomerular filtration rate (eGFR) 30-59 ml/min/1.73 m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History consistent with type 1 diabetes&#xD;
&#xD;
          2. Known secondary cause of hypertension&#xD;
&#xD;
          3. One minute standing systolic BP &lt;110 mmHg&#xD;
&#xD;
          4. Arm circumference too large to allow accurate blood pressure measurement with&#xD;
             available devices&#xD;
&#xD;
          5. Cardiovascular event or procedure or hospitalization for unstable angina within the&#xD;
             past 3 months&#xD;
&#xD;
          6. Symptomatic heart failure within the past 6 months or left ventricular ejection&#xD;
             fraction (by any method) &lt;35% within the past 6 months&#xD;
&#xD;
          7. ALT or AST levels more than twice the upper limit of the normal range or active liver&#xD;
             diseases&#xD;
&#xD;
          8. Dialysis, kidney transplantation, eGFR &lt;30 ml/min/1.73 m2, or serum creatinine &gt;2.0&#xD;
             mg/dl&#xD;
&#xD;
          9. Proteinuria&#xD;
&#xD;
         10. Previous diagnosis of polycystic kidney disease or glomerulonephritis&#xD;
&#xD;
         11. A medical condition likely to limit survival to less than 5 years&#xD;
&#xD;
         12. Any factors judged by the clinic team to be likely to limit adherence to interventions&#xD;
&#xD;
         13. Failure to obtain informed consent from participant&#xD;
&#xD;
         14. Currently participating in another intervention study&#xD;
&#xD;
         15. Currently living with another BPROAD participant&#xD;
&#xD;
         16. Pregnancy, currently trying to become pregnant, or of child-bearing potential and not&#xD;
             using birth control&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Guang Ning, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai Jiao Tong University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ruijin hospital, Shanghai Jiaotong University School of Medicine</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200025</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>December 16, 2018</study_first_submitted>
  <study_first_submitted_qc>January 15, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 17, 2019</study_first_posted>
  <last_update_submitted>May 21, 2023</last_update_submitted>
  <last_update_submitted_qc>May 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai Jiao Tong University School of Medicine</investigator_affiliation>
    <investigator_full_name>Guang Ning</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03808311
org study id: Ruijin-2018-138-2
nct id: NCT03808311
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a multicenter, open-label, parallel-group, randomized controlled trial that will be
      conducted across mainland China. This trial will test the primary hypothesis of whether an
      intensive treatment strategy (a systolic blood pressure target of <120 mmHg) is more
      effective than a standard treatment strategy (a systolic blood pressure target of <140 mmHg)
      in reducing the risk of major cardiovascular disease (non-fatal stroke, non-fatal myocardial
      infarction, treated or hospitalized heart failure, and cardiovascular deaths) over a
      follow-up period of up to 5 years among patients with a history of diabetes and elevated
      systolic blood pressure. The secondary hypotheses are to compare the intensive blood pressure
      treatment strategy with the standard treatment strategy on dementia and cognitive function,
      individual components of the primary hypothesis, all-cause mortality, kidney outcomes,
      quality of life, and injurious falls, et al.
The trial will recruit 12,702 patients from approximately 200 hospitals within the China
      Diabetes Clinical Research Network. Eligible criteria include men and women aged ≥50 years;
      type 2 diabetes mellitus; elevated systolic blood pressure; and a history of clinical
      cardiovascular disease or increased risk for cardiovascular disease. Main exclusion criteria
      include known secondary cause of hypertension, symptomatic heart failure, end-stage renal
      disease, and other serious illness. The proposed trial has 90% statistical power to detect a
      20% reduction (hazard ratio of 0.80) in major cardiovascular disease between intensive and
      standard treatment groups at a 2-sided significance level of 0.05.

      To achieve the proposed study objectives, the following specific aims will be accomplished:

        1. Recruit 12,702 study participants who meet the eligibility criteria and randomly assign
           6,351 to the intensive blood pressure treatment and 6,351 to the standard blood pressure
           treatment groups;

        2. Achieve and maintain two-level targets of systolic blood pressure (<120 mmHg vs. <140
           mmHg) with a mean systolic blood pressure difference of ≥15 mmHg;

        3. Employ a study-wide strategy to encourage standard of care for all participants for the
           treatment of type 2 diabetes and dyslipidemia other than blood pressure;

        4. Obtain clinical data on study outcomes for up to 60 months of follow-up among all trial
           participants;

        5. Perform strict quality control procedures for intervention and data collection;

        6. Conduct data analysis according to the intention-to-treat principle; and

        7. Disseminate the study findings to influence clinical practice and clinical guidelines.

      Findings from this trial will provide evidence as to whether intensive blood pressure
      management to achieve a systolic blood pressure target of <120 mmHg has additional benefits
      over standard management of systolic blood pressure <140 mmHg. These findings will help in
      the development of clinical guidelines for blood pressure management among patients with type
      2 diabetes and will have important clinical impact.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Major cardiovascular events
time frame: 5 years
description: Time to the first occurrence of any of the following: non-fatal stroke, non-fatal myocardial infarction, hospitalized or treated heart failure, or cardiovascular deaths
measure: A composite of the primary outcome and all-cause mortality
time frame: 5 years
description: Time to the first occurrence of any of the following: non-fatal stroke, non-fatal MI, hospitalized or treated heart failure, or death
measure: Macrovascular outcome
time frame: 5 years
description: Time to the first occurrence of any of the following: non-fatal stroke, non-fatal MI, hospitalized or treated heart failure, cardiovascular deaths, treated or hospitalized unstable angina, or any cardiovascular revascularization procedures
measure: Major coronary artery diseases
time frame: 5 years
description: Time to the first occurrence of any of the following: non-fatal MI, treated or hospitalized unstable angina, revascularization of coronary arteries, or deaths due to coronary artery diseases
measure: Total stroke
time frame: 5 years
description: Fatal and non-fatal stroke
measure: Heart failure
time frame: 5 years
description: Hospitalized or treated heart failure, or heart failure death
measure: Cardiovascular death
time frame: 5 years
description: Deaths due to cardiovascular causes
measure: Total mortality
time frame: 5 years
description: Deaths due to any causes
measure: Cognitive function
time frame: 5 years
description: Incidence of all-cause dementia
measure: Health related quality of life
time frame: 5 years
description: Evaluated with HQoL scales such as Short Form 12 Health Survey Questionnaire
measure: Kidney outcomes
time frame: 5 years
description: Progression of CKD, development of CKD, and incident albuminuria
measure: All cardiovascular revascularization procedures
time frame: 5 years
measure: Treated or hospitalized unstable angina
time frame: 5 years
measure: Retinopathy
time frame: 5 years
measure: Transient ischemic attack (TIA)
time frame: 5 years
measure: Left ventricular hypertrophy (LVH)
time frame: 5 years
measure: Atrial fibrillation or flutter
time frame: 5 years
measure: All cancers
time frame: 5 years
description: Time to the first occurrence of any types of cancer
measure: Cost-effectiveness
time frame: 5 years
description: The incremental cost per quality adjusted life year (QALY) gained. QALYs will be measured by the EuroQol-5 Dimensions (EQ-5D) questionnaire.
arm group label: Intensive BP treatment arm
arm group type: Experimental
description: Participants in the intensive BP treatment arm will be treated to a systolic BP target of <120 mmHg.
arm group label: Standard BP treatment arm
arm group type: Other
description: Participants in the standard BP treatment arm will be treated to a systolic BP target of <140 mmHg.
intervention type: Other
intervention name: Treatment strategy regarding different systolic BP goals
description: The trial will test a treatment strategy question regarding different systolic BP goals and not test specific medications. Therefore, the BP treatment protocol is flexible in terms of the choice and doses of anti-hypertensive medications as long as systolic BP levels are within targets (<120 mmHg in the intensive arm and <140 mmHg in the standard arm).
arm group label: Intensive BP treatment arm
arm group label: Standard BP treatment arm
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Guang Ning, MD, PhD
role: Principal Investigator
affiliation: Shanghai Jiao Tong University School of Medicine
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Shanghai Jiao Tong University School of Medicine
investigator full name: Guang Ning
investigator title: Professor
mesh term: Diabetes Mellitus
sharing ipd: Undecided