<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/NCT03011775</url>
  </required_header>
  <id_info>
    <org_study_id>CT-18-06-2012</org_study_id>
    <nct_id>NCT03011775</nct_id>
  </id_info>
  <brief_title>Effect of Pioglitazone on Insulin Resistance, Atherosclerosis Progression and Clinical Course of Coronary Heart Disease</brief_title>
  <acronym>EFFORT</acronym>
  <official_title>Effect of Pioglitazone on Insulin Resistance, Progression of Atherosclerosis and Clinical Course of Coronary Heart Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ukrainian Medical Stomatological Academy</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ukrainian Medical Stomatological Academy</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pioglitazone, a medication of thiazolidinedione group, is capable of triggering the&#xD;
      peroxisome proliferator-activated receptors (PPAR-γ). Activation of receptor PPAR-γ regulates&#xD;
      carbohydrate and lipid metabolism, immune and inflammatory responses in heart tissues.&#xD;
&#xD;
      Our aim will to study the effect of pioglitazone on insulin resistance, the clinical course&#xD;
      of atherosclerosis and coronary heart disease (CHD).&#xD;
&#xD;
      The study will include 43 patients with coronary artery disease. Patients will be divided&#xD;
      into the study group - 20 patients, in whom pioglitazone will be included in the combined&#xD;
      therapy at a dose of 15 mg 1 time per day in the morning, and the control group - 23 patients&#xD;
      receiving standard complex drug therapy over 6 months. Patients will be underwent clinical&#xD;
      examination, ultrasound of neck vessels, study of carbohydrate and lipid metabolism.&#xD;
&#xD;
      The end primary points of the study will be the onset of death due to myocardial infarction,&#xD;
      coronary revascularization procedures (coronary artery bypass grafting (CABG) or percutaneous&#xD;
      coronary intervention (PCI)), or hospitalization for acute coronary syndrome (ACS) or&#xD;
      unstable angina (UA).&#xD;
&#xD;
      Predefined secondary end points included carotic atherosclerotic leisure (carotic&#xD;
      intima-media thickness, diameter of stenosis, presents of atherosclerotic plaque), systemic&#xD;
      inflammation level (the level of C reactive protein), lipid metabolism (levels of serum total&#xD;
      cholesterol, triglycerides, high and low density lipoproteins), level of insulin resistance (&#xD;
      oral glucose tolerance test, blood glucose).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will include 43 people aged between 45 and 68 who suffered from ischemic heart&#xD;
      disease. Before starting the study, all participants will give written informed consent, will&#xD;
      be obtained of the Commission on Bioethics at Ukrainian Medical Stomatological Academy.&#xD;
      Inclusion criteria will be as follows: stable exertional angina, type 2 diabetes mellitus&#xD;
      (DM) without receiving injectable antidiabetic drugs. Exclusion criteria will be: the&#xD;
      presence of myocardial infarction history, intervention, malignant arterial hypertension&#xD;
      (AH), chronic heart failure (HF) of III-IV functional class (FC), systemic connective tissue&#xD;
      diseases, cancer and oncohematological diseases, severe infectious diseases, chronic&#xD;
      inflammatory diseases, history of acute cerebrovascular accidents, disorders of cardiac&#xD;
      rhythm by atrial fibrillation type. The end study will be the primary points: the onset of&#xD;
      death due to myocardial infarction, coronary revascularization procedures (coronary artery&#xD;
      bypass grafting (CABG) or percutaneous coronary intervention (PCI)), or hospitalization for&#xD;
      acute coronary syndrome (ACS) or unstable angina (UA).&#xD;
&#xD;
      The diagnosis of CHD in patients will confirmed by the presence of FC I-III angina according&#xD;
      to the classification of the Canadian Cardiovascular Society and the phenomena of circulatory&#xD;
      insufficiency according to the classification of New York Heart Association (NYHA). Bicycle&#xD;
      ergometry will perform on &quot;Veloergotest 05&quot; (Ukraine) via step increasing loading capacity&#xD;
      with a consequent increase under control of electrocardiogram (ECG) and BP. The force of step&#xD;
      I will be 150 kgm / min (25 W); II - 300 kgm / min (50 W); III - 450 kgm / min (75 W); IV -&#xD;
      600 kgm / min (100 W); V - 750 kgm / min (125 W); VI - 900 kgm / min (150 W), the duration of&#xD;
      each step was 3 minutes. Tolerance of CHD patients to exercise will calculate from the value&#xD;
      of the threshold load capacity and volume of work performed. The threshold load capacity of&#xD;
      150 kgm / min (25 W) was considered very low and consistent with angina FC IV; 300 kgm / min&#xD;
      (50 W) - low, FC III; 450-600 kgm / min (75-100 W) - average, FC II; 750 kgm / min (125 W)&#xD;
      and above - high exercise capacity, FC I. The criteria will cease bicycle ergometry&#xD;
      termination conventional clinical or ECG signs of myocardial ischemia.&#xD;
&#xD;
      Prior to inclusion in the clinical trial, all patients will receive conventional treatment&#xD;
      and will screening examination to verify the diagnosis of coronary heart disease and type 2&#xD;
      diabetes.&#xD;
&#xD;
      After screening, we will selected 43 patients who received standard medical therapy complex:&#xD;
      isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day,&#xD;
      bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day.&#xD;
      Patients also will receive recommendations on diet and lifestyle changes. Patients will&#xD;
      receive the conventional treatment for at least one month to achieve stable parameters.&#xD;
&#xD;
      On the first day of the study, blood samples will take from all patients, clinical&#xD;
      examination was conducted. After clinical and laboratory studies, patients will randomized by&#xD;
      gender, age and severity of clinical manifestations of coronary heart disease. As a result of&#xD;
      randomization, patients will divide into the study group (n = 20) and control group (n = 23).&#xD;
      The complex therapy of the study group will include pioglitazone 15 mg 1 time per day in the&#xD;
      morning (&quot;Pioglar&quot;, Ranbaxy, India) for 6 months. Patients of the control group will continue&#xD;
      to receive only a standard set of drug therapy. Re-examination will carry out in 6 months.&#xD;
&#xD;
      The examination will include the collection of medical history and objective data (gender,&#xD;
      age, overweight and obesity, hypertension, type 2 diabetes). Patients will evaluate by&#xD;
      anthropometric indicators (height, weight, body mass index (BMI)), blood pressure - systolic&#xD;
      and diastolic (SBP and DBP), heart rate (HR) will measure, ECG will register.&#xD;
&#xD;
      In order to determine the status of vascular bed, patients will underwent ultrasonography&#xD;
      (US) of neck vessels on &quot;ULTIMA PA&quot;, sensor L5 - 12/40, in accordance with standard protocols&#xD;
      in B-mode on the three levels of vascular bed and bilaterally at the end of diastole: in the&#xD;
      proximal, medial and distal points at a distance of 1 cm from the bifurcation of the&#xD;
      posterior wall of the right and left common carotid artery (RCCA and LCCA, respectively) as&#xD;
      more distant from the transducer unit. Contour of the carotid arteries will register, their&#xD;
      inner lumen, indicators for ASP presence (size, localization) will record, as well as IMT of&#xD;
      the carotid arteries. IMT will measure as the distance between the first and the second&#xD;
      echogenic lines of located site according to the procedure Pignoli P. et al. The diameter of&#xD;
      RCCA, LCCA, and the internal carotid artery (ICA) will assess at the end of systole and&#xD;
      diastole as the distance between the IMT. Normal IMT will consider less than 0.9 mm; CCA IMT&#xD;
      &gt; 1.4 mm was evaluated as ASP, and in the range of 1.0-1.3 mm as the thickening of IMT (ESH,&#xD;
      ESC, 2007). The standard criteria for the diagnosis of hemodynamically significant stenosis&#xD;
      are the narrowing of the arterial lumen by more than 50%.&#xD;
&#xD;
      The volume of laboratory tests will includ general clinical and biochemical blood analysis.&#xD;
      For the control of carbohydrate metabolism glycemic profiles will study determining fasting&#xD;
      glucose and after 1 hour after taking 75 g of glucose (oral glucose tolerance test, OGTT) via&#xD;
      glucose oxidase method; hyperglycemic factor will calculate. In all patients lipid profile&#xD;
      will studied: total cholesterol (TC), triglycerides (TG) and cholesterol of high-density&#xD;
      lipoproteins (HDL) (&quot;Diakon-DS&quot;, Russia), content of cholesterol in low-density lipoproteins&#xD;
      (LDL) and very low density lipoproteins (VLDL) will calculate, as well as atherogenic factor&#xD;
      (AF). Study of the inflammatory response will conduct by determining the concentration of&#xD;
      basic biomarkers - high-sensitivity C-reactive protein (hs-CRP, &quot;DRG&quot;, USA), human tissue&#xD;
      inhibitor of metalloproteinase-1 (TIMP-1, &quot;eBioscience&quot;, Austria) according to the&#xD;
      manufacturer's protocols of test systems via immunoenzyme method. The presence of&#xD;
      microalbuminuria will determine using test strips &quot;Mikroalbufan&quot; (&quot;Lachema&quot;, Czech Republic),&#xD;
      the ratio albumin / creatinine in urine will calculated.&#xD;
&#xD;
      Statistical processing will perform using software &quot;Statistica 6.0&quot; (StatSoft, USA) with&#xD;
      calculation of average (M) and standard error of the average (m). Methods of descriptive&#xD;
      statistics will use, comparison of performance in groups will perform by parametric&#xD;
      (Student's t-test) and non-parametric (Pearson χ2 test, Fisher's exact test, Mann-Whitney&#xD;
      test) statistics. For all types of analysis the differences at p &lt;0.05 will consider&#xD;
      statistically significant.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">September 2015</completion_date>
  <primary_completion_date type="Actual">June 2014</primary_completion_date>
  <phase>Phase 4</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Сardiovascular Death</measure>
    <time_frame>Baseline and 1 year</time_frame>
    <description>Number of Participants with cardiovascular death</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Coronary Artery Bypass [Coronary Revascularization]</measure>
    <time_frame>Baseline and 1 year</time_frame>
    <description>Number of Participants with revascularization coronary procedures (coronary artery bypass grafting)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cardiovascular Hospitalization</measure>
    <time_frame>Baseline and 1 year</time_frame>
    <description>Number of Participants with acute coronary syndrome (ACS) or unstable angina (UA)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percutaneous Coronary Intervention [Coronary Revascularization]</measure>
    <time_frame>Baseline and 1 year</time_frame>
    <description>Number of Participants with incidence of percutaneous coronary intervention.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and Tolerability 1</measure>
    <time_frame>Baseline, 6 month and 1 year</time_frame>
    <description>Liver injury: mean values of ALT</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and Tolerability 2</measure>
    <time_frame>Baseline, 6 month and 1 year</time_frame>
    <description>Liver injury: mean levels of total bilirubin</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and Tolerability 3</measure>
    <time_frame>Baseline and 1 year</time_frame>
    <description>Kidney injury: mean values of the microalbuminuria</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and Tolerability 4</measure>
    <time_frame>Baseline and 1 year</time_frame>
    <description>Kidneys injury: mean values of creatinine</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Thickness of the Intima-media Complex</measure>
    <time_frame>Baseline, 6 month and 1 year</time_frame>
    <description>Mean thickness of carotid intima-media complex</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diameter of Stenosis [Carotic Atherosclerotic Lesions]</measure>
    <time_frame>Baseline and 1 year</time_frame>
    <description>Mean diameters of the stenosis of the right and left common carotid arteries</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Carotic Atherosclerotic Lesions</measure>
    <time_frame>Baseline and 1 year</time_frame>
    <description>Number of Participants with presence of atherosclerotic plaque of the intima media of common carotid artery greater than 1.4 mm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic Inflammation Level</measure>
    <time_frame>Baseline and 1 year</time_frame>
    <description>Number of Participants with C-reactive protein level above 3 mg/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipid Metabolism 1</measure>
    <time_frame>Baseline, 6 month and 1 year</time_frame>
    <description>Mean levels of total serum cholesterol</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipid Metabolism 2</measure>
    <time_frame>Baseline, 6 month and 1 year</time_frame>
    <description>Mean values of the triglyceride levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lipid Metabolism 3</measure>
    <time_frame>Baseline and 1 year</time_frame>
    <description>Lipoproteine fractions:mean values of high-density lipoproteins and low density lipoproteins</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Level of Insulin Resistance 1</measure>
    <time_frame>6 months</time_frame>
    <description>Oral glucose tolerance test: number of Participants with impaired glucose tolerance</description>
  </other_outcome>
  <other_outcome>
    <measure>Level of Insulin Resistance 2</measure>
    <time_frame>Baseline and 6 months</time_frame>
    <description>Mean levels of blood glucose</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">43</enrollment>
  <condition>Adverse Effect</condition>
  <condition>Atherosclerosis, Coronary</condition>
  <condition>Insulin Resistance Syndrome</condition>
  <arm_group>
    <arm_group_label>Pioglitazone + Standard Care</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard Care</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pioglitazone 15 mg Tablet</intervention_name>
    <description>Pioglar (Ranbaxy India):1 tablet per day in the morning for 6 months</description>
    <arm_group_label>Pioglitazone + Standard Care</arm_group_label>
    <other_name>Oral hypoglycemic agent</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Isosorbide Dinitrate 10Mg Tablet</intervention_name>
    <description>1-2 tablets 2 times a day</description>
    <arm_group_label>Pioglitazone + Standard Care</arm_group_label>
    <arm_group_label>Standard Care</arm_group_label>
    <other_name>Antianginal, vasodilator agent</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acetylsalicylic Acid 75Mg Tablet</intervention_name>
    <description>1 tablet per a day</description>
    <arm_group_label>Pioglitazone + Standard Care</arm_group_label>
    <arm_group_label>Standard Care</arm_group_label>
    <other_name>NSAID and antiplatelet agent</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bisoprolol Fumarate 2.5 MG Oral Tablet</intervention_name>
    <description>1 tablet per a day</description>
    <arm_group_label>Pioglitazone + Standard Care</arm_group_label>
    <arm_group_label>Standard Care</arm_group_label>
    <other_name>Lowering high blood pressure agent</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rosuvastatin Calcium 20 MG Oral Tablet</intervention_name>
    <description>1 tablet per a day</description>
    <arm_group_label>Pioglitazone + Standard Care</arm_group_label>
    <arm_group_label>Standard Care</arm_group_label>
    <other_name>Lipid- lowering agent</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ramipril 5 MG</intervention_name>
    <description>1 tablet per a day</description>
    <arm_group_label>Pioglitazone + Standard Care</arm_group_label>
    <arm_group_label>Standard Care</arm_group_label>
    <other_name>ACE inhibitor</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  stable exertional angina,&#xD;
&#xD;
          -  type 2 diabetes mellitus (DM) without receiving injectable antidiabetic drugs&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  the presence of myocardial infarction history, intervention;&#xD;
&#xD;
          -  malignant arterial hypertension (AH);&#xD;
&#xD;
          -  chronic heart failure (HF) of III-IV functional class (FC);&#xD;
&#xD;
          -  systemic connective tissue diseases;&#xD;
&#xD;
          -  cancer and oncohematological diseases, severe infectious diseases, chronic&#xD;
             inflammatory diseases;&#xD;
&#xD;
          -  history of acute cerebrovascular accidents;&#xD;
&#xD;
          -  disorders of cardiac rhythm by atrial fibrillation type.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>68 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Ukrainian Medical Stomatological Academy</name>
      <address>
        <city>Poltava</city>
        <zip>36011</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ukraine</country>
  </location_countries>
  <reference>
    <citation>Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Struijker Boudier HA, Zanchetti A, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Kjeldsen SE, Erdine S, Narkiewicz K, Kiowski W, Agabiti-Rosei E, Ambrosioni E, Cifkova R, Dominiczak A, Fagard R, Heagerty AM, Laurent S, Lindholm LH, Mancia G, Manolis A, Nilsson PM, Redon J, Schmieder RE, Struijker-Boudier HA, Viigimaa M, Filippatos G, Adamopoulos S, Agabiti-Rosei E, Ambrosioni E, Bertomeu V, Clement D, Erdine S, Farsang C, Gaita D, Kiowski W, Lip G, Mallion JM, Manolis AJ, Nilsson PM, O'Brien E, Ponikowski P, Redon J, Ruschitzka F, Tamargo J, van Zwieten P, Viigimaa M, Waeber B, Williams B, Zamorano JL, The task force for the management of arterial hypertension of the European Society of Hypertension, The task force for the management of arterial hypertension of the European Society of Cardiology. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2007 Jun;28(12):1462-536. doi: 10.1093/eurheartj/ehm236. Epub 2007 Jun 11. No abstract available.</citation>
    <PMID>17562668</PMID>
  </reference>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>December 29, 2016</study_first_submitted>
  <study_first_submitted_qc>January 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <results_first_submitted>October 7, 2021</results_first_submitted>
  <results_first_submitted_qc>January 9, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">March 10, 2022</results_first_posted>
  <last_update_submitted>January 9, 2022</last_update_submitted>
  <last_update_submitted_qc>January 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ukrainian Medical Stomatological Academy</investigator_affiliation>
    <investigator_full_name>Igor Kaydashev</investigator_full_name>
    <investigator_title>Head of Internal Medicine Department #3</investigator_title>
  </responsible_party>
  <keyword>Pioglitazone, Insulin Resistance</keyword>
  <keyword>Atherosclerosis, Coronary Heart Disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Atherosclerosis</mesh_term>
    <mesh_term>Coronary Disease</mesh_term>
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Insulin Resistance</mesh_term>
    <mesh_term>Metabolic Syndrome</mesh_term>
    <mesh_term>Disease Progression</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Pioglitazone</mesh_term>
    <mesh_term>Hypoglycemic Agents</mesh_term>
    <mesh_term>Ramipril</mesh_term>
    <mesh_term>Bisoprolol</mesh_term>
    <mesh_term>Isosorbide</mesh_term>
    <mesh_term>Isosorbide Dinitrate</mesh_term>
    <mesh_term>Isosorbide-5-mononitrate</mesh_term>
    <mesh_term>Vasodilator Agents</mesh_term>
    <mesh_term>Platelet Aggregation Inhibitors</mesh_term>
    <mesh_term>Rosuvastatin Calcium</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Pioglitazone + Standard Care</title>
          <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
        </group>
        <group group_id="P2">
          <title>Standard Care</title>
          <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Pioglitazone + Standard Care</title>
          <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
        </group>
        <group group_id="B2">
          <title>Standard Care</title>
          <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
            <count group_id="B2" value="23"/>
            <count group_id="B3" value="43"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="41"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54.6" spread="1.15"/>
                    <measurement group_id="B2" value="53" spread="1.36"/>
                    <measurement group_id="B3" value="53.7" spread="5.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="43"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Ukraine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Сardiovascular Death</title>
        <description>Number of Participants with cardiovascular death</description>
        <time_frame>Baseline and 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pioglitazone + Standard Care</title>
            <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
        </group_list>
        <measure>
          <title>Сardiovascular Death</title>
          <description>Number of Participants with cardiovascular death</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Coronary Artery Bypass [Coronary Revascularization]</title>
        <description>Number of Participants with revascularization coronary procedures (coronary artery bypass grafting)</description>
        <time_frame>Baseline and 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pioglitazone + Standard Care</title>
            <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
        </group_list>
        <measure>
          <title>Coronary Artery Bypass [Coronary Revascularization]</title>
          <description>Number of Participants with revascularization coronary procedures (coronary artery bypass grafting)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cardiovascular Hospitalization</title>
        <description>Number of Participants with acute coronary syndrome (ACS) or unstable angina (UA)</description>
        <time_frame>Baseline and 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pioglitazone + Standard Care</title>
            <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
        </group_list>
        <measure>
          <title>Cardiovascular Hospitalization</title>
          <description>Number of Participants with acute coronary syndrome (ACS) or unstable angina (UA)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percutaneous Coronary Intervention [Coronary Revascularization]</title>
        <description>Number of Participants with incidence of percutaneous coronary intervention.</description>
        <time_frame>Baseline and 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pioglitazone + Standard Care</title>
            <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day&#xD;
During the observation of mortality from all-cause mortality, serious adverse events, other (Not Including Serious) adverse events among patients of study groups not recorded.</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day During the observation of mortality from all-cause mortality, serious adverse events, other (Not Including Serious) adverse events among patients of control groups not recorded.</description>
          </group>
        </group_list>
        <measure>
          <title>Percutaneous Coronary Intervention [Coronary Revascularization]</title>
          <description>Number of Participants with incidence of percutaneous coronary intervention.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Safety and Tolerability 1</title>
        <description>Liver injury: mean values of ALT</description>
        <time_frame>Baseline, 6 month and 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pioglitazone + Standard Care</title>
            <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
        </group_list>
        <measure>
          <title>Safety and Tolerability 1</title>
          <description>Liver injury: mean values of ALT</description>
          <units>units per liter (U/L)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.4" spread="2.4"/>
                    <measurement group_id="O2" value="26.9" spread="2.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean values of ALT in 6 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.4" spread="2.1"/>
                    <measurement group_id="O2" value="26.1" spread="1.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean values of ALT in 1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.9" spread="1.9"/>
                    <measurement group_id="O2" value="23.9" spread="1.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Safety and Tolerability 2</title>
        <description>Liver injury: mean levels of total bilirubin</description>
        <time_frame>Baseline, 6 month and 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pioglitazone + Standard Care</title>
            <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: Pioglar (Ranbaxy India):1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
Ramipril 5 MG: 1 tablet per a day</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
Ramipril 5 MG: 1 tablet per a day</description>
          </group>
        </group_list>
        <measure>
          <title>Safety and Tolerability 2</title>
          <description>Liver injury: mean levels of total bilirubin</description>
          <units>μmol/l</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.3" spread="1.3"/>
                    <measurement group_id="O2" value="10.8" spread="1.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean values of total bilirubin in 6 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.4" spread="1.02"/>
                    <measurement group_id="O2" value="12.7" spread="1.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean values of total bilirubin in 1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.7" spread="1.6"/>
                    <measurement group_id="O2" value="15.0" spread="5.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Safety and Tolerability 3</title>
        <description>Kidney injury: mean values of the microalbuminuria</description>
        <time_frame>Baseline and 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pioglitazone + Standard Care</title>
            <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day&#xD;
During the observation of mortality from all-cause mortality, serious adverse events, other (Not Including Serious) adverse events among patients of study groups not recorded.</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day During the observation of mortality from all-cause mortality, serious adverse events, other (Not Including Serious) adverse events among patients of control groups not recorded.</description>
          </group>
        </group_list>
        <measure>
          <title>Safety and Tolerability 3</title>
          <description>Kidney injury: mean values of the microalbuminuria</description>
          <units>mg/mol</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.44" spread="4.28"/>
                    <measurement group_id="O2" value="41.1" spread="4.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.10" spread="5.00"/>
                    <measurement group_id="O2" value="37.70" spread="4.48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Safety and Tolerability 4</title>
        <description>Kidneys injury: mean values of creatinine</description>
        <time_frame>Baseline and 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pioglitazone + Standard Care</title>
            <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
        </group_list>
        <measure>
          <title>Safety and Tolerability 4</title>
          <description>Kidneys injury: mean values of creatinine</description>
          <units>μmol/l</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Mean values of creatinine in men baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="105.6" spread="38.5"/>
                    <measurement group_id="O2" value="102.3" spread="43.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean values of creatinine in men in 1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.0" spread="21.1"/>
                    <measurement group_id="O2" value="82.0" spread="14.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean values of creatinine in women baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.8" spread="8.8"/>
                    <measurement group_id="O2" value="88.2" spread="11.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean values of creatinine in women in 1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.5" spread="8.1"/>
                    <measurement group_id="O2" value="77.5" spread="18.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Thickness of the Intima-media Complex</title>
        <description>Mean thickness of carotid intima-media complex</description>
        <time_frame>Baseline, 6 month and 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pioglitazone + Standard Care</title>
            <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
        </group_list>
        <measure>
          <title>Thickness of the Intima-media Complex</title>
          <description>Mean thickness of carotid intima-media complex</description>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Mean thickness of the right carotid intima-media baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.08" spread="0.17"/>
                    <measurement group_id="O2" value="0.98" spread="0.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean thickness of the right carotid intima-media in 6 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.05" spread="0.13"/>
                    <measurement group_id="O2" value="0.97" spread="0.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean thickness of the right carotid intima-media in 1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.01" spread="0.02"/>
                    <measurement group_id="O2" value="1.01" spread="0.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean thickness of the left carotid intima-media baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" spread="0.18"/>
                    <measurement group_id="O2" value="1.0" spread="0.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean thickness of the left carotid intima-media in 6 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.06" spread="0.13"/>
                    <measurement group_id="O2" value="1.00" spread="0.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean thickness of the left carotid intima-media in 1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.02" spread="0.02"/>
                    <measurement group_id="O2" value="0.97" spread="0.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <method_desc>The threshold for statistical significance was P value of .05</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Diameter of Stenosis [Carotic Atherosclerotic Lesions]</title>
        <description>Mean diameters of the stenosis of the right and left common carotid arteries</description>
        <time_frame>Baseline and 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pioglitazone + Standard Care</title>
            <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
        </group_list>
        <measure>
          <title>Diameter of Stenosis [Carotic Atherosclerotic Lesions]</title>
          <description>Mean diameters of the stenosis of the right and left common carotid arteries</description>
          <units>mm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Mean diameter of the stenosis of the right common carotid artery baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.8" spread="3.1"/>
                    <measurement group_id="O2" value="8.7" spread="2.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean diameter of the stenosis of the right common carotid artery in 1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.0" spread="1.8"/>
                    <measurement group_id="O2" value="4.8" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean diameter of the stenosis of the left common carotid artery baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.6" spread="3.6"/>
                    <measurement group_id="O2" value="10.1" spread="3.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean diameter of the stenosis of the left common carotid artery in 1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.1" spread="1.7"/>
                    <measurement group_id="O2" value="5.6" spread="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&gt;0.05</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Carotic Atherosclerotic Lesions</title>
        <description>Number of Participants with presence of atherosclerotic plaque of the intima media of common carotid artery greater than 1.4 mm</description>
        <time_frame>Baseline and 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pioglitazone + Standard Care</title>
            <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
        </group_list>
        <measure>
          <title>Carotic Atherosclerotic Lesions</title>
          <description>Number of Participants with presence of atherosclerotic plaque of the intima media of common carotid artery greater than 1.4 mm</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Systemic Inflammation Level</title>
        <description>Number of Participants with C-reactive protein level above 3 mg/L</description>
        <time_frame>Baseline and 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pioglitazone + Standard Care</title>
            <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
        </group_list>
        <measure>
          <title>Systemic Inflammation Level</title>
          <description>Number of Participants with C-reactive protein level above 3 mg/L</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>In 1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&gt;0.05</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Lipid Metabolism 1</title>
        <description>Mean levels of total serum cholesterol</description>
        <time_frame>Baseline, 6 month and 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pioglitazone + Standard Care</title>
            <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
        </group_list>
        <measure>
          <title>Lipid Metabolism 1</title>
          <description>Mean levels of total serum cholesterol</description>
          <units>mmol / l</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Mean values of the total cholesterol level baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.27" spread="0.2"/>
                    <measurement group_id="O2" value="5.28" spread="1.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean values of the total cholesterol level in 6 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5" spread="0.2"/>
                    <measurement group_id="O2" value="4.3" spread="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean values of the total cholesterol level in 1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5" spread="0.2"/>
                    <measurement group_id="O2" value="4.3" spread="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Lipid Metabolism 2</title>
        <description>Mean values of the triglyceride levels</description>
        <time_frame>Baseline, 6 month and 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pioglitazone + Standard Care</title>
            <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
        </group_list>
        <measure>
          <title>Lipid Metabolism 2</title>
          <description>Mean values of the triglyceride levels</description>
          <units>1 mmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Mean values of triglyceride baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.69" spread="0.1"/>
                    <measurement group_id="O2" value="0.61" spread="0.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean values of triglyceride in 6 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.72" spread="0.40"/>
                    <measurement group_id="O2" value="0.73" spread="0.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean values of triglyceride in 1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9" spread="0.1"/>
                    <measurement group_id="O2" value="0.7" spread="0.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Lipid Metabolism 3</title>
        <description>Lipoproteine fractions:mean values of high-density lipoproteins and low density lipoproteins</description>
        <time_frame>Baseline and 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pioglitazone + Standard Care</title>
            <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
        </group_list>
        <measure>
          <title>Lipid Metabolism 3</title>
          <description>Lipoproteine fractions:mean values of high-density lipoproteins and low density lipoproteins</description>
          <units>mmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Mean values of high-density lipoproteins in men baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8" spread="0.2"/>
                    <measurement group_id="O2" value="0.9" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean values of high-density lipoproteins in men in 1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" spread="0.3"/>
                    <measurement group_id="O2" value="1.0" spread="0.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean values of high-density lipoproteins in women baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9" spread="0.3"/>
                    <measurement group_id="O2" value="1.1" spread="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean values of high-density lipoproteins in women in 1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2" spread="0.2"/>
                    <measurement group_id="O2" value="1.0" spread="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean values of low density lipoproteins in men baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.9" spread="0.7"/>
                    <measurement group_id="O2" value="4.4" spread="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean values of low density lipoproteins in men in 1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.9" spread="0.5"/>
                    <measurement group_id="O2" value="3.0" spread="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean values of low density lipoproteins in women baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5" spread="0.8"/>
                    <measurement group_id="O2" value="3.5" spread="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mean values of low density lipoproteins in women in 1 year</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.3" spread="0.8"/>
                    <measurement group_id="O2" value="2.7" spread="0.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Level of Insulin Resistance 1</title>
        <description>Oral glucose tolerance test: number of Participants with impaired glucose tolerance</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pioglitazone + Standard Care</title>
            <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Insulin Resistance 1</title>
          <description>Oral glucose tolerance test: number of Participants with impaired glucose tolerance</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Number of Participants with glucose level in the range of 7.8 to 11 mmol/L baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of Participants with glucose level in the range of 7.8 to 11 mmol/L in 6 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of Participants with glucose level above 11 mmol/L baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of Participants with glucose level above 11 mmol/L in 6 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.05</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Level of Insulin Resistance 2</title>
        <description>Mean levels of blood glucose</description>
        <time_frame>Baseline and 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pioglitazone + Standard Care</title>
            <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
          <group group_id="O2">
            <title>Standard Care</title>
            <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
          </group>
        </group_list>
        <measure>
          <title>Level of Insulin Resistance 2</title>
          <description>Mean levels of blood glucose</description>
          <units>mmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0" spread="0.1"/>
                    <measurement group_id="O2" value="5.9" spread="0.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>In 6 month</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.97" spread="0.20"/>
                    <measurement group_id="O2" value="5.60" spread="0.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>=0.3</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Pioglitazone + Standard Care</title>
          <description>20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.&#xD;
Pioglitazone 15 mg Tablet: 1 tablet per day in the morning for 6 months&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
        </group>
        <group group_id="E2">
          <title>Standard Care</title>
          <description>23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.&#xD;
Isosorbide Dinitrate 10Mg Tablet: 1-2 tablets 2 times a day&#xD;
Acetylsalicylic Acid 75Mg Tablet: 1 tablet per a day&#xD;
Bisoprolol Fumarate 2.5 MG Oral Tablet: 1 tablet per a day&#xD;
Rosuvastatin Calcium 20 MG Oral Tablet: 1 tablet per a day&#xD;
ramipril 5 MG: 1 tablet per a day</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Prof. Igor Kaidashev</name_or_title>
      <organization>Ukrainian Medical Stomatological Academy</organization>
      <phone>+380505858953</phone>
      <email>kaydashevip@gmail.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03011775
org study id: CT-18-06-2012
nct id: NCT03011775
lead sponsor: 
has dmc: Yes
Pioglitazone, a medication of thiazolidinedione group, is capable of triggering the
      peroxisome proliferator-activated receptors (PPAR-γ). Activation of receptor PPAR-γ regulates
      carbohydrate and lipid metabolism, immune and inflammatory responses in heart tissues.

      Our aim will to study the effect of pioglitazone on insulin resistance, the clinical course
      of atherosclerosis and coronary heart disease (CHD).

      The study will include 43 patients with coronary artery disease. Patients will be divided
      into the study group - 20 patients, in whom pioglitazone will be included in the combined
      therapy at a dose of 15 mg 1 time per day in the morning, and the control group - 23 patients
      receiving standard complex drug therapy over 6 months. Patients will be underwent clinical
      examination, ultrasound of neck vessels, study of carbohydrate and lipid metabolism.

      The end primary points of the study will be the onset of death due to myocardial infarction,
      coronary revascularization procedures (coronary artery bypass grafting (CABG) or percutaneous
      coronary intervention (PCI)), or hospitalization for acute coronary syndrome (ACS) or
      unstable angina (UA).

      Predefined secondary end points included carotic atherosclerotic leisure (carotic
      intima-media thickness, diameter of stenosis, presents of atherosclerotic plaque), systemic
      inflammation level (the level of C reactive protein), lipid metabolism (levels of serum total
      cholesterol, triglycerides, high and low density lipoproteins), level of insulin resistance (
      oral glucose tolerance test, blood glucose).
The study will include 43 people aged between 45 and 68 who suffered from ischemic heart
      disease. Before starting the study, all participants will give written informed consent, will
      be obtained of the Commission on Bioethics at Ukrainian Medical Stomatological Academy.
      Inclusion criteria will be as follows: stable exertional angina, type 2 diabetes mellitus
      (DM) without receiving injectable antidiabetic drugs. Exclusion criteria will be: the
      presence of myocardial infarction history, intervention, malignant arterial hypertension
      (AH), chronic heart failure (HF) of III-IV functional class (FC), systemic connective tissue
      diseases, cancer and oncohematological diseases, severe infectious diseases, chronic
      inflammatory diseases, history of acute cerebrovascular accidents, disorders of cardiac
      rhythm by atrial fibrillation type. The end study will be the primary points: the onset of
      death due to myocardial infarction, coronary revascularization procedures (coronary artery
      bypass grafting (CABG) or percutaneous coronary intervention (PCI)), or hospitalization for
      acute coronary syndrome (ACS) or unstable angina (UA).

      The diagnosis of CHD in patients will confirmed by the presence of FC I-III angina according
      to the classification of the Canadian Cardiovascular Society and the phenomena of circulatory
      insufficiency according to the classification of New York Heart Association (NYHA). Bicycle
      ergometry will perform on "Veloergotest 05" (Ukraine) via step increasing loading capacity
      with a consequent increase under control of electrocardiogram (ECG) and BP. The force of step
      I will be 150 kgm / min (25 W); II - 300 kgm / min (50 W); III - 450 kgm / min (75 W); IV -
      600 kgm / min (100 W); V - 750 kgm / min (125 W); VI - 900 kgm / min (150 W), the duration of
      each step was 3 minutes. Tolerance of CHD patients to exercise will calculate from the value
      of the threshold load capacity and volume of work performed. The threshold load capacity of
      150 kgm / min (25 W) was considered very low and consistent with angina FC IV; 300 kgm / min
      (50 W) - low, FC III; 450-600 kgm / min (75-100 W) - average, FC II; 750 kgm / min (125 W)
      and above - high exercise capacity, FC I. The criteria will cease bicycle ergometry
      termination conventional clinical or ECG signs of myocardial ischemia.

      Prior to inclusion in the clinical trial, all patients will receive conventional treatment
      and will screening examination to verify the diagnosis of coronary heart disease and type 2
      diabetes.

      After screening, we will selected 43 patients who received standard medical therapy complex:
      isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day,
      bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day.
      Patients also will receive recommendations on diet and lifestyle changes. Patients will
      receive the conventional treatment for at least one month to achieve stable parameters.

      On the first day of the study, blood samples will take from all patients, clinical
      examination was conducted. After clinical and laboratory studies, patients will randomized by
      gender, age and severity of clinical manifestations of coronary heart disease. As a result of
      randomization, patients will divide into the study group (n = 20) and control group (n = 23).
      The complex therapy of the study group will include pioglitazone 15 mg 1 time per day in the
      morning ("Pioglar", Ranbaxy, India) for 6 months. Patients of the control group will continue
      to receive only a standard set of drug therapy. Re-examination will carry out in 6 months.

      The examination will include the collection of medical history and objective data (gender,
      age, overweight and obesity, hypertension, type 2 diabetes). Patients will evaluate by
      anthropometric indicators (height, weight, body mass index (BMI)), blood pressure - systolic
      and diastolic (SBP and DBP), heart rate (HR) will measure, ECG will register.

      In order to determine the status of vascular bed, patients will underwent ultrasonography
      (US) of neck vessels on "ULTIMA PA", sensor L5 - 12/40, in accordance with standard protocols
      in B-mode on the three levels of vascular bed and bilaterally at the end of diastole: in the
      proximal, medial and distal points at a distance of 1 cm from the bifurcation of the
      posterior wall of the right and left common carotid artery (RCCA and LCCA, respectively) as
      more distant from the transducer unit. Contour of the carotid arteries will register, their
      inner lumen, indicators for ASP presence (size, localization) will record, as well as IMT of
      the carotid arteries. IMT will measure as the distance between the first and the second
      echogenic lines of located site according to the procedure Pignoli P. et al. The diameter of
      RCCA, LCCA, and the internal carotid artery (ICA) will assess at the end of systole and
      diastole as the distance between the IMT. Normal IMT will consider less than 0.9 mm; CCA IMT
      > 1.4 mm was evaluated as ASP, and in the range of 1.0-1.3 mm as the thickening of IMT (ESH,
      ESC, 2007). The standard criteria for the diagnosis of hemodynamically significant stenosis
      are the narrowing of the arterial lumen by more than 50%.

      The volume of laboratory tests will includ general clinical and biochemical blood analysis.
      For the control of carbohydrate metabolism glycemic profiles will study determining fasting
      glucose and after 1 hour after taking 75 g of glucose (oral glucose tolerance test, OGTT) via
      glucose oxidase method; hyperglycemic factor will calculate. In all patients lipid profile
      will studied: total cholesterol (TC), triglycerides (TG) and cholesterol of high-density
      lipoproteins (HDL) ("Diakon-DS", Russia), content of cholesterol in low-density lipoproteins
      (LDL) and very low density lipoproteins (VLDL) will calculate, as well as atherogenic factor
      (AF). Study of the inflammatory response will conduct by determining the concentration of
      basic biomarkers - high-sensitivity C-reactive protein (hs-CRP, "DRG", USA), human tissue
      inhibitor of metalloproteinase-1 (TIMP-1, "eBioscience", Austria) according to the
      manufacturer's protocols of test systems via immunoenzyme method. The presence of
      microalbuminuria will determine using test strips "Mikroalbufan" ("Lachema", Czech Republic),
      the ratio albumin / creatinine in urine will calculated.

      Statistical processing will perform using software "Statistica 6.0" (StatSoft, USA) with
      calculation of average (M) and standard error of the average (m). Methods of descriptive
      statistics will use, comparison of performance in groups will perform by parametric
      (Student's t-test) and non-parametric (Pearson χ2 test, Fisher's exact test, Mann-Whitney
      test) statistics. For all types of analysis the differences at p <0.05 will consider
      statistically significant.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Сardiovascular Death
time frame: Baseline and 1 year
description: Number of Participants with cardiovascular death
measure: Coronary Artery Bypass [Coronary Revascularization]
time frame: Baseline and 1 year
description: Number of Participants with revascularization coronary procedures (coronary artery bypass grafting)
measure: Cardiovascular Hospitalization
time frame: Baseline and 1 year
description: Number of Participants with acute coronary syndrome (ACS) or unstable angina (UA)
measure: Percutaneous Coronary Intervention [Coronary Revascularization]
time frame: Baseline and 1 year
description: Number of Participants with incidence of percutaneous coronary intervention.
measure: Safety and Tolerability 1
time frame: Baseline, 6 month and 1 year
description: Liver injury: mean values of ALT
measure: Safety and Tolerability 2
time frame: Baseline, 6 month and 1 year
description: Liver injury: mean levels of total bilirubin
measure: Safety and Tolerability 3
time frame: Baseline and 1 year
description: Kidney injury: mean values of the microalbuminuria
measure: Safety and Tolerability 4
time frame: Baseline and 1 year
description: Kidneys injury: mean values of creatinine
measure: Thickness of the Intima-media Complex
time frame: Baseline, 6 month and 1 year
description: Mean thickness of carotid intima-media complex
measure: Diameter of Stenosis [Carotic Atherosclerotic Lesions]
time frame: Baseline and 1 year
description: Mean diameters of the stenosis of the right and left common carotid arteries
measure: Carotic Atherosclerotic Lesions
time frame: Baseline and 1 year
description: Number of Participants with presence of atherosclerotic plaque of the intima media of common carotid artery greater than 1.4 mm
measure: Systemic Inflammation Level
time frame: Baseline and 1 year
description: Number of Participants with C-reactive protein level above 3 mg/L
measure: Lipid Metabolism 1
time frame: Baseline, 6 month and 1 year
description: Mean levels of total serum cholesterol
measure: Lipid Metabolism 2
time frame: Baseline, 6 month and 1 year
description: Mean values of the triglyceride levels
measure: Lipid Metabolism 3
time frame: Baseline and 1 year
description: Lipoproteine fractions:mean values of high-density lipoproteins and low density lipoproteins
measure: Level of Insulin Resistance 1
time frame: 6 months
description: Oral glucose tolerance test: number of Participants with impaired glucose tolerance
measure: Level of Insulin Resistance 2
time frame: Baseline and 6 months
description: Mean levels of blood glucose
arm group label: Pioglitazone + Standard Care
arm group type: Experimental
description: 20 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes. Included pioglitazone 15 mg 1 time per day in the morning for 6 months.
arm group label: Standard Care
arm group type: Other
description: 23 patients who received standard medical therapy complex: isosorbide dinitrate 10-20 mg 2 times a day, acetylsalicylic acid 75 mg 1 time a day, bisoprolol 2.5 mg 1 time a day, rosuvastatin 20 mg 1 time a day, ramipril 5 mg 1 time a day. Patients also received recommendations on diet and lifestyle changes.
intervention type: Drug
intervention name: Pioglitazone 15 mg Tablet
description: Pioglar (Ranbaxy India):1 tablet per day in the morning for 6 months
arm group label: Pioglitazone + Standard Care
other name: Oral hypoglycemic agent
intervention type: Drug
intervention name: Isosorbide Dinitrate 10Mg Tablet
description: 1-2 tablets 2 times a day
arm group label: Pioglitazone + Standard Care
arm group label: Standard Care
other name: Antianginal, vasodilator agent
intervention type: Drug
intervention name: Acetylsalicylic Acid 75Mg Tablet
description: 1 tablet per a day
arm group label: Pioglitazone + Standard Care
arm group label: Standard Care
other name: NSAID and antiplatelet agent
intervention type: Drug
intervention name: Bisoprolol Fumarate 2.5 MG Oral Tablet
description: 1 tablet per a day
arm group label: Pioglitazone + Standard Care
arm group label: Standard Care
other name: Lowering high blood pressure agent
intervention type: Drug
intervention name: Rosuvastatin Calcium 20 MG Oral Tablet
description: 1 tablet per a day
arm group label: Pioglitazone + Standard Care
arm group label: Standard Care
other name: Lipid- lowering agent
intervention type: Drug
intervention name: Ramipril 5 MG
description: 1 tablet per a day
arm group label: Pioglitazone + Standard Care
arm group label: Standard Care
other name: ACE inhibitor
criteria: 
gender: All
minimum age: 45 Years
maximum age: 68 Years
healthy volunteers: No
facility: 
country: Ukraine
citation: Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Struijker Boudier HA, Zanchetti A, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Kjeldsen SE, Erdine S, Narkiewicz K, Kiowski W, Agabiti-Rosei E, Ambrosioni E, Cifkova R, Dominiczak A, Fagard R, Heagerty AM, Laurent S, Lindholm LH, Mancia G, Manolis A, Nilsson PM, Redon J, Schmieder RE, Struijker-Boudier HA, Viigimaa M, Filippatos G, Adamopoulos S, Agabiti-Rosei E, Ambrosioni E, Bertomeu V, Clement D, Erdine S, Farsang C, Gaita D, Kiowski W, Lip G, Mallion JM, Manolis AJ, Nilsson PM, O'Brien E, Ponikowski P, Redon J, Ruschitzka F, Tamargo J, van Zwieten P, Viigimaa M, Waeber B, Williams B, Zamorano JL, The task force for the management of arterial hypertension of the European Society of Hypertension, The task force for the management of arterial hypertension of the European Society of Cardiology. 2007 Guidelines for the management of arterial hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2007 Jun;28(12):1462-536. doi: 10.1093/eurheartj/ehm236. Epub 2007 Jun 11. No abstract available.
PMID: 17562668
responsible party type: Principal Investigator
investigator affiliation: Ukrainian Medical Stomatological Academy
investigator full name: Igor Kaydashev
investigator title: Head of Internal Medicine Department #3
mesh term: Heart Diseases
mesh term: Atherosclerosis
mesh term: Coronary Disease
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Insulin Resistance
mesh term: Metabolic Syndrome
mesh term: Disease Progression
mesh term: Aspirin
mesh term: Pioglitazone
mesh term: Hypoglycemic Agents
mesh term: Ramipril
mesh term: Bisoprolol
mesh term: Isosorbide
mesh term: Isosorbide Dinitrate
mesh term: Isosorbide-5-mononitrate
mesh term: Vasodilator Agents
mesh term: Platelet Aggregation Inhibitors
mesh term: Rosuvastatin Calcium
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 