<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/NCT02208869</url>
  </required_header>
  <id_info>
    <org_study_id>SSCRES0179</org_study_id>
    <nct_id>NCT02208869</nct_id>
  </id_info>
  <brief_title>Russian Familial Hypercholesterolemia Registry</brief_title>
  <acronym>RuFH</acronym>
  <official_title>Prospective Russian Study Evaluating the Extent of Underdiagnosed and Undertreated of Familial Hypercholesterolaemia in the Population</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Russian Cardiology Research and Production Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Russian Cardiology Research and Production Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      True prevalence of FH in the Russian Federation is unknown which leads to low percentage of&#xD;
      diagnosed and treated cases. Research is needed to determine the prevalence of FH, specific&#xD;
      diagnostic algorithms and optimal treatment strategies. The main aim of the present study is&#xD;
      to evaluate the extent to which FH is underdiagnosed and undertreated in the Russian&#xD;
      Federation for reduction of cardiovascular risk related to atherosclerosis in the country.&#xD;
&#xD;
      As a first step, total cholesterol (TC) and low-density lipoprotein (LDL-C) levels will be&#xD;
      determined in a random sample from Moscow population (n=18000). It is expected that TC ≥ 7.5&#xD;
      mmol/L will be detected in 10% of cohort. During 2014, approximately 500 patients will pass&#xD;
      through non-invasive clinical examination at the Russian Cardiology Research and Production&#xD;
      Center, including patient demographics, past medical history, family history of&#xD;
      hypercholesterolemia, physical findings, current lipid-lowering therapies, blood tests,&#xD;
      genetic analysis, echocardiography, carotid duplex ultrasound and exercise SPECT imaging in&#xD;
      selected cases. On the basis of the Moscow Program four major Federal Medical Centers will be&#xD;
      involved, and FH Registry will be created as a national, multi-center initiative to screen FH&#xD;
      patients, control their diagnosis and management, and track clinical-reported outcomes over&#xD;
      time.&#xD;
&#xD;
      Establishment of National Guidelines for the diagnosis and treatment of FH on the basis of&#xD;
      these data and implementation those into clinical practice in different regions of Russia&#xD;
      will allow improving patient care. As an expected outcome, this program will raise awareness&#xD;
      and increase appropriate assessment and treatment of FH patients in Russia, leading to a&#xD;
      timely detection of the disease and therapy initiation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      *Design. We have chosen a randomly selected cohort of individuals who have been tested in the&#xD;
      Moscow office of the &quot;INVITRO&quot; Laboratory on the basis of advertising campaign held in&#xD;
      September, 2013, for the purpose of TC level measurement and determination of cardiovascular&#xD;
      risk with the use of SCORE chart. The operator from the &quot;INVITRO&quot; Laboratory identified&#xD;
      potential FH patients based on TC (≥7.5 mmol/L) or LDL-C (≥4.9 mmol/L) values.&#xD;
&#xD;
      Following identification, the potentially eligible participants suspected for FH are sent a&#xD;
      notification letter describing the patient's high cholesterol level, at-atherosclerosis risk&#xD;
      status and need for additional screening on the basis of the Russian Cardiology Research and&#xD;
      Production Center. Those who give preliminary agreement for participation in the Program are&#xD;
      invited to the Institution, where, after signing the ICF, they will undergo clinical&#xD;
      (biochemical, echo, duplex scan) and genetic testing. Those individuals refusing to&#xD;
      participate in the Program will be taken into account with fixing the reason of unwillingness&#xD;
      to participate.&#xD;
&#xD;
      Patients under the age of 18 will be enrolled only with the explicit consent of a parent or&#xD;
      legal guardian. All participants will be provided with the information about the Russian FH&#xD;
      Community and Russian FH Registry.&#xD;
&#xD;
      All included subjects will be provided with a screening questionnaire querying the patient&#xD;
      demographics, past medical history, patient FH history and diagnosis with FH type&#xD;
      heterozygous or homozygous, family history of hypercholesterolemia, physical examination&#xD;
      findings, current lipid-lowering therapies, and patients' contact information for further&#xD;
      follow-up. After initialization of online data capture form (Electronic Medical System), the&#xD;
      information will be also entered in the system. Blood and gene banks will be formed; analysis&#xD;
      of echocardiography data for aortic valve stenosis, carotid duplex ultrasound for&#xD;
      atherosclerosis burden, and exercise SPECT imaging in selected cases of suspected coronary&#xD;
      heart disease (CHD) will be performed during the baseline visit. Patients diagnosed with FH&#xD;
      on the basis of Dutch Lipid Clinic Network, Simon Broome Criteria and genetic testing will be&#xD;
      provided information about screening of first-degree relatives, and additional educational&#xD;
      materials about FH (under development).&#xD;
&#xD;
      To determine the true number of heterozygous forms among individuals with a probable&#xD;
      diagnosis of FH molecular genetic testing is planned. When a causative mutation is found in&#xD;
      the index case, a genetic test will be offered to all first-degree relatives.&#xD;
&#xD;
      Enrolled patients will be asked to update information at annually intervals. Since the last&#xD;
      date of data entry, occurrence of major adverse cardiovascular events (acute coronary&#xD;
      syndromes, stroke, myocardial revascularization, peripheral revascularization, cardiovascular&#xD;
      death), changes in medications, hospitalizations to any reasons, genetic testing, laboratory&#xD;
      values, and all-cause mortality will be reviewed.&#xD;
&#xD;
      Follow-up data will be collected yearly following initial enrollment. Updated information on&#xD;
      quality of life will be collected. Annual reminder emails will be sent to all patients to&#xD;
      call the following physician.&#xD;
&#xD;
      We estimate that at one site during one year (2014-2015) we will screen 500 patients eligible&#xD;
      for the participation from the potentially eligible 1505 selected from 18000 individuals.&#xD;
&#xD;
        -  Five leading Federal Medical Centers in different regions of Russia will be involved at&#xD;
           the first two steps of the Program:&#xD;
&#xD;
             1. Federal State Institution &quot;Russian Cardiology Research and Production Center&quot; of&#xD;
                the Health Ministry of the Russian Federation (Moscow); First line Federal Medical&#xD;
                Centers&#xD;
&#xD;
             2. Samara State Medical University (Samara);&#xD;
&#xD;
             3. Research Institute of Internal Medicine (Novosibirsk);&#xD;
&#xD;
             4. Saint-Petersburg State University (Sokolov Center for atherosclerosis and lipid&#xD;
                disorders in Clinical Hospital №122 (Saint Petersburg));&#xD;
&#xD;
             5. Chelyabinsk State Medical Academy (Chelyabinsk)&#xD;
&#xD;
        -  A total of three scheduled visits are planned during the course of this study. Visit 1&#xD;
           will occur during the Screening Period (Part A). Patients who enter the Screening Period&#xD;
           (Part A) will be signing the ICF, instructed to follow regional dietary guidelines for&#xD;
           the duration of the study. They will undergo clinical (biochemical, ultra-sound, duplex&#xD;
           scan) and exercise SPECT imaging if applicable. Those individuals refusing to&#xD;
           participate in the study will be taken into account with fixing the reason of&#xD;
           unwillingness to participate.&#xD;
&#xD;
      All included subjects will be provided with a screening questionnaire querying the patient&#xD;
      demographics, past medical history, patient FH history and diagnosis with FH type&#xD;
      heterozygous or homozygous, family history of hypercholesterolemia, physical examination&#xD;
      findings, current lipid-lowering therapies, and patients' contact information for further&#xD;
      follow-up. After initialization of online data capture form (Electronic Medical System), the&#xD;
      information will be also entered in the system.&#xD;
&#xD;
      For the patients with FH diagnosed on the basis of Dutch Lipid Clinic Network and/or Simon&#xD;
      Broome Criteria or genetic testing Visit 2 will occur in a one month period. Visit 3 will&#xD;
      occur in RussianCRPC in a one year±10 days period. At the scheduled visits update of the&#xD;
      medical information, including monitoring of adverse cardiovascular events occurrence,&#xD;
      changes in medications, and blood sampling, will be performed.&#xD;
&#xD;
        -  Examination procedures at the scheduled visits:&#xD;
&#xD;
             1. Signing the informed consent form (ICF)&#xD;
&#xD;
             2. Filling the questionnaires to determine the classical cardiovascular risk factors,&#xD;
                past medical history and treatment&#xD;
&#xD;
             3. Applying Dutch Lipid Clinic Network (DLCN) and Simon Broome Register (SBR) criteria&#xD;
&#xD;
             4. Maintaining Electronic Medical System by physicians participating in the Program&#xD;
&#xD;
             5. Blood sampling for TC, triglycerides (TG), LDL-C, HDL-C, Lp(a), high-sensitivity&#xD;
                C-reactive protein (hsCRP), PCSK9 measurement&#xD;
&#xD;
             6. Genetic testing (mutations in the LDLR, apolipoprotein B (apoB), PCSK9 genes)&#xD;
&#xD;
             7. Echocardiography for the assessment of ascending aorta and aortic valve&#xD;
&#xD;
             8. Duplex scanning of the carotid arteries for the assessment of intima-media&#xD;
                thickness and plaques' characteristics&#xD;
&#xD;
             9. Exercise SPECT imaging in patients suspicious for coronary disease&#xD;
&#xD;
            10. Annual evaluation of cardiovascular events (myocardial infarction, stroke,&#xD;
                cardiovascular death, non-cardiovascular death, hospitalization due to acute&#xD;
                coronary syndrome, heart failure, arterial revascularization procedures&#xD;
                (percutaneous coronary intervention, coronary artery bypass grafting, endovascular&#xD;
                or surgical revascularization in carotid arteries or lower extremities), aortic&#xD;
                valve replacement.&#xD;
&#xD;
        -  FH patients at these 1-st line Sites who meet inclusion criteria as described in the&#xD;
           Methods section will be eligible to enroll. The same algorithm as described above will&#xD;
           be initiated. Specialized staff from the Russian Cardiology Research and Production&#xD;
           Complex (as a Core Center) will monitor the effectiveness and credibility of the&#xD;
           undertaken work. Filling in the Electronic Medical System (eCRF) will be checked by the&#xD;
           staff from the Core Center, and each year teleconferences will be held between the&#xD;
           Sites-Participants of the Program.&#xD;
&#xD;
        -  Perspectives: since 2018 ¬ the next phases of the Program will include recruitment of&#xD;
           new set of Clinics, Policlinics and Institutions across Russia with specialized lipid&#xD;
           clinics that could demonstrate acceptable feasibility for patient enrollment and&#xD;
           engagement.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date>January 2014</start_date>
  <completion_date type="Anticipated">December 31, 2026</completion_date>
  <primary_completion_date type="Actual">December 31, 2017</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>10 Years</target_duration>
  <primary_outcome>
    <measure>Prevalence of FH patients in the Russian Federation</measure>
    <time_frame>at baseline</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with heterozygous and homozygous forms of FH in Russia</measure>
    <time_frame>at baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Distribution of lipoprotein(a) in individuals diagnosed with definite and probable FH.</measure>
    <time_frame>at baseline</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of carotid atherosclerosis, aortic valve stenosis and coronary heart disease in Russian patients with FH</measure>
    <time_frame>at baseline</time_frame>
    <description>Assessment of carotid atherosclerosis will be performed with the use of carotid duplex scanning.&#xD;
Presence and severity of aortic valve stenosis will be evaluated with echocardiography.&#xD;
Exercise radionuclide myocardial perfusion imaging with single-photon emission computed tomography (SPECT) will be used for the diagnosis of myocardial ischemia in patients suspicious for CHD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mutations in following genes: low-density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B (apoB)</measure>
    <time_frame>At baseline</time_frame>
    <description>Genetic testing for FH-causing mutation in patients with probable and definite FH</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Russian Registry of individuals with FH</measure>
    <time_frame>up to 10 years</time_frame>
    <description>Contribution in the formation of the Russian Health Ministry legislative acts concerning significance of FH as a socially and medically important disease with appropriate management strategies.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prognosis of individuals with FH</measure>
    <time_frame>at 1, 3, 5, 10 years</time_frame>
    <description>Incidence of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, revascularization procedures (cardiac, carotid, or peripheral), hospitalizations due to unstable angina pectoris or heart failure, all-cause mortality, diabetes in participants without baseline diabetes, new or recurrent cancers.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Clinical and diagnostic significance of Dutch Lipid Clinic Network criteria and Simon Broome Registry criteria for diagnosis of FH in Russian population</measure>
    <time_frame>up to 5 years</time_frame>
    <description>Clinical and diagnostic significance of Dutch Lipid Clinic Network criteria and Simon Broome Registry criteria for the diagnosis of FH in Russia.</description>
  </other_outcome>
  <other_outcome>
    <measure>Family Health Team model and cascade testing in individuals with FH</measure>
    <time_frame>up to 3 years</time_frame>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">1000</enrollment>
  <condition>Familial Hypercholesterolemia</condition>
  <arm_group>
    <arm_group_label>Patients diagnosed with FH</arm_group_label>
    <description>Subjects of both sexes above the age of 18 with TC ≥7.5 mmol/L or LDL-C ≥4.9 mmol/L will be included in the Program. Clinical diagnosis of FH will be established using both the Dutch and the British criteria.&#xD;
Those with secondary causes of hypercholesterolemia, such as untreated diabetes mellitus (HbA1c &gt;8%) or hypothyroidism (thyroid-stimulating hormone &gt;1.5 upper normal limit), renal failure (creatinine clearance &lt;30 ml/min), holestatic liver diseases, including biliary cirrhosis, tumors with an active process in the last 5 years will be excluded from the study.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      whole blood, serum, white cells, urine&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Russian cohort of individuals who have been tested in the offices of the &quot;INVITRO&quot;&#xD;
        Laboratory on the basis of advertising campaign for the purpose of total cholesterol level&#xD;
        measurement and determination of cardiovascular risk with the use of SCORE chart.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Total cholesterol ≥7.5 mmol/L or LDL-C ≥4.9 mmol/L (pretreatment levels)&#xD;
&#xD;
          -  Familial hypercholesterolemia defined as: a. Mutation in the LDL receptor and/or the&#xD;
             ApoB gene and/or the PCSK9 gene; or b. clinical diagnosis of heterozygous FH (HeFH)&#xD;
             according to the Dutch Lipid Network Criteria or Simon Broom Criteria&#xD;
&#xD;
          -  Patients with genetic mutation of FH&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  uncontrolled primary hypothyroidism (thyroid stimulating hormone (TSH) &gt;1.5 x upper&#xD;
             limit of normal (ULN)),&#xD;
&#xD;
          -  nephrotic syndrome and/or renal dysfunction (scrum creatinine &gt;2.0 mg/dL or 160mmol/l,&#xD;
             creatinine clearance &lt;15 ml/min) at screening.&#xD;
&#xD;
          -  uncontrolled diabetes mellitus (Glycated hemoglobin &gt;8.5%)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>7 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Valery Kukharchuk, MD, DMSc</last_name>
    <role>Study Chair</role>
    <affiliation>Russian Cardiology Research and Production Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Igor Sergienko, MD, DMSc</last_name>
    <role>Study Director</role>
    <affiliation>Russian Cardiology Research and Production Center</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Marat Ezhov, MD, DMSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Russian Cardiology Research and Production Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Marat Ezhov, MD, PhD</last_name>
    <phone>+79104137499</phone>
    <email>Marat_Ezhov@mail.ru</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Igor Sergienko, MD, DMSc</last_name>
    <phone>+79031492253</phone>
    <email>igorcardio@mail.ru</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Chelyabinsk State Medical Academy</name>
      <address>
        <city>Chelyabinsk</city>
        <zip>454092</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Igor Shaposhnik, MD, DMSc</last_name>
      <phone>+79088235120</phone>
      <email>shaposhnik@yandex.ru</email>
    </contact>
    <contact_backup>
      <last_name>Bogdanov Dmitriy, MD, PhD</last_name>
      <phone>+79124773437</phone>
      <email>dmitrchel@mail.com.ru</email>
    </contact_backup>
    <investigator>
      <last_name>Igor Shaposhnik, MD, DMSc</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Bogdanov Dmitriy, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Salashenko Aleksey, MD&lt; PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Genkel Vadim, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>EI Chazov National Medical Research Center of Cardiology</name>
      <address>
        <city>Moscow</city>
        <zip>121552</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marat Ezhov, MD, PhD</last_name>
      <phone>+791041374993558</phone>
      <email>Marat_Ezhov@mail.ru</email>
    </contact>
    <contact_backup>
      <last_name>Igor Sergienko, MD, PhD</last_name>
      <phone>+79031492253</phone>
      <email>igorcardio@mail.ru</email>
    </contact_backup>
    <investigator>
      <last_name>Vladmir Malakhov, MD,PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Diana Nozadze, MD,PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Natalya Gornyakova, MD,PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Alexey Ansheles, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Tatiana Balakhonova, MD, DMSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Olga Pogorelova, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Maria Tripoten, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Grigory Heymets, PhD, DSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Narek Tmoyan, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ulyana Chubykina, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Svetlana Bliznyuk, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Tatyana Rozhkova, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Novosibirsk Research Institute of Internal Medicine, Institute of Internal Medicine Siberian Branch of the Russian Academy of Medical Sciences</name>
      <address>
        <city>Novosibirsk</city>
        <zip>630089</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Mikhail Voevoda, MD, DMSc</last_name>
      <phone>+79139505088</phone>
      <email>mvoevoda@ya.ru</email>
    </contact>
    <contact_backup>
      <last_name>Yulia Ragino, MD, DMSc</last_name>
      <phone>+79537799704</phone>
      <email>ragino@mail.ru</email>
    </contact_backup>
    <investigator>
      <last_name>Mikhail Voevoda, MD, DMSc</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Yulia Ragino, MD, DMSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Elena Shakhtshneider, MD, DMSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ksenia Makarenkova, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Elena Antonova, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Elena Voevoda, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Saint-Petersburg State University and North-West State Medical University n.a. I.I.Mechnikov</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Viktor Gurevich, MD, DMSc</last_name>
      <phone>+78125599759</phone>
      <email>vktrgurevich@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Soreya Urazgildeeva, MD, DMSc</last_name>
      <phone>+78125599759</phone>
      <email>docsau64@yandex.ru</email>
    </contact_backup>
    <investigator>
      <last_name>Viktor Gurevich, MD, DMSc</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Soreya Urazgildeeva, MD, DMSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Alexey Tregubov, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Maria Muzalevskaya, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Samara State Medical University</name>
      <address>
        <city>Samara</city>
        <zip>443099</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Mikhail Kachkovsky, MD, PhD</last_name>
      <phone>+79171187181</phone>
      <email>kma10@yandex.ru</email>
    </contact>
    <contact_backup>
      <last_name>Olesya Rubanenko, MD, PhD</last_name>
      <phone>+79371887780</phone>
      <email>olesya.rubanenko@gmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Mikhail Kachkovsky, MD, DMSc</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Olesya Rubanenko, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Dmitry Duplyakov, MD, DMSc</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <link>
    <url>http://noatero.ru/ru/programma-noa</url>
    <description>Program for identification of individuals at high and very high risk of cardiovascular complications</description>
  </link>
  <reference>
    <citation>M. S. Safarova, I. V. Sergienko, M. V. Ezhov, A. E. Semenova, M. A. Kachkovskiy, I. I. Shaposhnik, V. S. Gurevich, M. I. Voevoda, Y. P. Nikitin, V. V. Kuharchuk, Yu. A. Karpov Russian research program for early diagnosis and treatment of familial hypercholesterolaemia: Rationale and Design of the Russian FH Registry (RuFH). Journal of ATHEROSCLEROSIS AND DYSLIPIDAEMIAS 3: 7-15, 2014 (in Russian)</citation>
  </reference>
  <reference>
    <citation>Ezhov MV SI, Duplyakov DV, Abashina OE, Kachkovsky MA, Shaposhnik II, Genkel VV, Gurevich VS, Urazgildeeva SA, Tregubov AV, Konovalova TB, Muzalevskaya MV, Voevoda MI, Bazhan SS, Makarenkova KV, Timoshenko OV, Ragino YI, Urvantseva IA, Cozhocar KG, Sokolov AA, Boeva OI, Bolotova EV, Kushnaryova YB, Kuznetsova TY, Korneva VA, Bogdanov DY, Chichina EE, Soloviev VM, Smolenskaya OG, Galyavich AS, Safarova MS, Popova AV, Malakhov VV, Ansheles AA, Nozadze DN, Semenova AE, Rozhkova TA, Solovéva EY, Gornyakova NB, Karpov YA, Kukharchuk VV. Results of the Russian research program on the diagnosis and treatment of patients with familial hypercholesterolemia. High prevalence, low awareness, poor adherence. Atherosclerosis and Dyslipidaemias An official Journal of the Russian National Atherosclerosis Society (RNAS) 2017;2:5-15.</citation>
  </reference>
  <results_reference>
    <citation>EAS Familial Hypercholesterolaemia Studies Collaboration, Vallejo-Vaz AJ, Akram A, Kondapally Seshasai SR, Cole D, Watts GF, Hovingh GK, Kastelein JJ, Mata P, Raal FJ, Santos RD, Soran H, Freiberger T, Abifadel M, Aguilar-Salinas CA, Alnouri F, Alonso R, Al-Rasadi K, Banach M, Bogsrud MP, Bourbon M, Bruckert E, Car J, Ceska R, Corral P, Descamps O, Dieplinger H, Do CT, Durst R, Ezhov MV, Fras Z, Gaita D, Gaspar IM, Genest J, Harada-Shiba M, Jiang L, Kayikcioglu M, Lam CS, Latkovskis G, Laufs U, Liberopoulos E, Lin J, Lin N, Maher V, Majano N, Marais AD, März W, Mirrakhimov E, Miserez AR, Mitchenko O, Nawawi H, Nilsson L, Nordestgaard BG, Paragh G, Petrulioniene Z, Pojskic B, Reiner Ž, Sahebkar A, Santos LE, Schunkert H, Shehab A, Slimane MN, Stoll M, Su TC, Susekov A, Tilney M, Tomlinson B, Tselepis AD, Vohnout B, Widén E, Yamashita S, Catapano AL, Ray KK. Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes: Rationale and design of the global EAS Familial Hypercholesterolaemia Studies Collaboration. Atheroscler Suppl. 2016;22:1-32. doi: 10.1016/j.atherosclerosissup.2016.10.001.</citation>
  </results_reference>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>August 2, 2014</study_first_submitted>
  <study_first_submitted_qc>August 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 5, 2014</study_first_posted>
  <last_update_submitted>November 1, 2022</last_update_submitted>
  <last_update_submitted_qc>November 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Russian Cardiology Research and Production Center</investigator_affiliation>
    <investigator_full_name>Marat Vladislavovich Ezhov (MV Ezhov, MD, PhD, DMSc)</investigator_full_name>
    <investigator_title>Leading Researcher, MD, DMSc</investigator_title>
  </responsible_party>
  <keyword>familial hypercholesterolemia</keyword>
  <keyword>cholesterol</keyword>
  <keyword>prevention</keyword>
  <keyword>registry</keyword>
  <keyword>atherosclerosis</keyword>
  <keyword>treatment</keyword>
  <keyword>prevalence</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperlipoproteinemia Type II</mesh_term>
    <mesh_term>Hypercholesterolemia</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02208869
org study id: SSCRES0179
nct id: NCT02208869
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
True prevalence of FH in the Russian Federation is unknown which leads to low percentage of
      diagnosed and treated cases. Research is needed to determine the prevalence of FH, specific
      diagnostic algorithms and optimal treatment strategies. The main aim of the present study is
      to evaluate the extent to which FH is underdiagnosed and undertreated in the Russian
      Federation for reduction of cardiovascular risk related to atherosclerosis in the country.

      As a first step, total cholesterol (TC) and low-density lipoprotein (LDL-C) levels will be
      determined in a random sample from Moscow population (n=18000). It is expected that TC ≥ 7.5
      mmol/L will be detected in 10% of cohort. During 2014, approximately 500 patients will pass
      through non-invasive clinical examination at the Russian Cardiology Research and Production
      Center, including patient demographics, past medical history, family history of
      hypercholesterolemia, physical findings, current lipid-lowering therapies, blood tests,
      genetic analysis, echocardiography, carotid duplex ultrasound and exercise SPECT imaging in
      selected cases. On the basis of the Moscow Program four major Federal Medical Centers will be
      involved, and FH Registry will be created as a national, multi-center initiative to screen FH
      patients, control their diagnosis and management, and track clinical-reported outcomes over
      time.

      Establishment of National Guidelines for the diagnosis and treatment of FH on the basis of
      these data and implementation those into clinical practice in different regions of Russia
      will allow improving patient care. As an expected outcome, this program will raise awareness
      and increase appropriate assessment and treatment of FH patients in Russia, leading to a
      timely detection of the disease and therapy initiation.
*Design. We have chosen a randomly selected cohort of individuals who have been tested in the
      Moscow office of the "INVITRO" Laboratory on the basis of advertising campaign held in
      September, 2013, for the purpose of TC level measurement and determination of cardiovascular
      risk with the use of SCORE chart. The operator from the "INVITRO" Laboratory identified
      potential FH patients based on TC (≥7.5 mmol/L) or LDL-C (≥4.9 mmol/L) values.

      Following identification, the potentially eligible participants suspected for FH are sent a
      notification letter describing the patient's high cholesterol level, at-atherosclerosis risk
      status and need for additional screening on the basis of the Russian Cardiology Research and
      Production Center. Those who give preliminary agreement for participation in the Program are
      invited to the Institution, where, after signing the ICF, they will undergo clinical
      (biochemical, echo, duplex scan) and genetic testing. Those individuals refusing to
      participate in the Program will be taken into account with fixing the reason of unwillingness
      to participate.

      Patients under the age of 18 will be enrolled only with the explicit consent of a parent or
      legal guardian. All participants will be provided with the information about the Russian FH
      Community and Russian FH Registry.

      All included subjects will be provided with a screening questionnaire querying the patient
      demographics, past medical history, patient FH history and diagnosis with FH type
      heterozygous or homozygous, family history of hypercholesterolemia, physical examination
      findings, current lipid-lowering therapies, and patients' contact information for further
      follow-up. After initialization of online data capture form (Electronic Medical System), the
      information will be also entered in the system. Blood and gene banks will be formed; analysis
      of echocardiography data for aortic valve stenosis, carotid duplex ultrasound for
      atherosclerosis burden, and exercise SPECT imaging in selected cases of suspected coronary
      heart disease (CHD) will be performed during the baseline visit. Patients diagnosed with FH
      on the basis of Dutch Lipid Clinic Network, Simon Broome Criteria and genetic testing will be
      provided information about screening of first-degree relatives, and additional educational
      materials about FH (under development).

      To determine the true number of heterozygous forms among individuals with a probable
      diagnosis of FH molecular genetic testing is planned. When a causative mutation is found in
      the index case, a genetic test will be offered to all first-degree relatives.

      Enrolled patients will be asked to update information at annually intervals. Since the last
      date of data entry, occurrence of major adverse cardiovascular events (acute coronary
      syndromes, stroke, myocardial revascularization, peripheral revascularization, cardiovascular
      death), changes in medications, hospitalizations to any reasons, genetic testing, laboratory
      values, and all-cause mortality will be reviewed.

      Follow-up data will be collected yearly following initial enrollment. Updated information on
      quality of life will be collected. Annual reminder emails will be sent to all patients to
      call the following physician.

      We estimate that at one site during one year (2014-2015) we will screen 500 patients eligible
      for the participation from the potentially eligible 1505 selected from 18000 individuals.

        -  Five leading Federal Medical Centers in different regions of Russia will be involved at
           the first two steps of the Program:

             1. Federal State Institution "Russian Cardiology Research and Production Center" of
                the Health Ministry of the Russian Federation (Moscow); First line Federal Medical
                Centers

             2. Samara State Medical University (Samara);

             3. Research Institute of Internal Medicine (Novosibirsk);

             4. Saint-Petersburg State University (Sokolov Center for atherosclerosis and lipid
                disorders in Clinical Hospital №122 (Saint Petersburg));

             5. Chelyabinsk State Medical Academy (Chelyabinsk)

        -  A total of three scheduled visits are planned during the course of this study. Visit 1
           will occur during the Screening Period (Part A). Patients who enter the Screening Period
           (Part A) will be signing the ICF, instructed to follow regional dietary guidelines for
           the duration of the study. They will undergo clinical (biochemical, ultra-sound, duplex
           scan) and exercise SPECT imaging if applicable. Those individuals refusing to
           participate in the study will be taken into account with fixing the reason of
           unwillingness to participate.

      All included subjects will be provided with a screening questionnaire querying the patient
      demographics, past medical history, patient FH history and diagnosis with FH type
      heterozygous or homozygous, family history of hypercholesterolemia, physical examination
      findings, current lipid-lowering therapies, and patients' contact information for further
      follow-up. After initialization of online data capture form (Electronic Medical System), the
      information will be also entered in the system.

      For the patients with FH diagnosed on the basis of Dutch Lipid Clinic Network and/or Simon
      Broome Criteria or genetic testing Visit 2 will occur in a one month period. Visit 3 will
      occur in RussianCRPC in a one year±10 days period. At the scheduled visits update of the
      medical information, including monitoring of adverse cardiovascular events occurrence,
      changes in medications, and blood sampling, will be performed.

        -  Examination procedures at the scheduled visits:

             1. Signing the informed consent form (ICF)

             2. Filling the questionnaires to determine the classical cardiovascular risk factors,
                past medical history and treatment

             3. Applying Dutch Lipid Clinic Network (DLCN) and Simon Broome Register (SBR) criteria

             4. Maintaining Electronic Medical System by physicians participating in the Program

             5. Blood sampling for TC, triglycerides (TG), LDL-C, HDL-C, Lp(a), high-sensitivity
                C-reactive protein (hsCRP), PCSK9 measurement

             6. Genetic testing (mutations in the LDLR, apolipoprotein B (apoB), PCSK9 genes)

             7. Echocardiography for the assessment of ascending aorta and aortic valve

             8. Duplex scanning of the carotid arteries for the assessment of intima-media
                thickness and plaques' characteristics

             9. Exercise SPECT imaging in patients suspicious for coronary disease

            10. Annual evaluation of cardiovascular events (myocardial infarction, stroke,
                cardiovascular death, non-cardiovascular death, hospitalization due to acute
                coronary syndrome, heart failure, arterial revascularization procedures
                (percutaneous coronary intervention, coronary artery bypass grafting, endovascular
                or surgical revascularization in carotid arteries or lower extremities), aortic
                valve replacement.

        -  FH patients at these 1-st line Sites who meet inclusion criteria as described in the
           Methods section will be eligible to enroll. The same algorithm as described above will
           be initiated. Specialized staff from the Russian Cardiology Research and Production
           Complex (as a Core Center) will monitor the effectiveness and credibility of the
           undertaken work. Filling in the Electronic Medical System (eCRF) will be checked by the
           staff from the Core Center, and each year teleconferences will be held between the
           Sites-Participants of the Program.

        -  Perspectives: since 2018 ¬ the next phases of the Program will include recruitment of
           new set of Clinics, Policlinics and Institutions across Russia with specialized lipid
           clinics that could demonstrate acceptable feasibility for patient enrollment and
           engagement.
observational model: Cohort
time perspective: Prospective
measure: Prevalence of FH patients in the Russian Federation
time frame: at baseline
measure: Number of patients with heterozygous and homozygous forms of FH in Russia
time frame: at baseline
measure: Distribution of lipoprotein(a) in individuals diagnosed with definite and probable FH.
time frame: at baseline
measure: Severity of carotid atherosclerosis, aortic valve stenosis and coronary heart disease in Russian patients with FH
time frame: at baseline
description: Assessment of carotid atherosclerosis will be performed with the use of carotid duplex scanning.
Presence and severity of aortic valve stenosis will be evaluated with echocardiography.
Exercise radionuclide myocardial perfusion imaging with single-photon emission computed tomography (SPECT) will be used for the diagnosis of myocardial ischemia in patients suspicious for CHD.
measure: Mutations in following genes: low-density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein B (apoB)
time frame: At baseline
description: Genetic testing for FH-causing mutation in patients with probable and definite FH
measure: Russian Registry of individuals with FH
time frame: up to 10 years
description: Contribution in the formation of the Russian Health Ministry legislative acts concerning significance of FH as a socially and medically important disease with appropriate management strategies.
measure: Prognosis of individuals with FH
time frame: at 1, 3, 5, 10 years
description: Incidence of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, revascularization procedures (cardiac, carotid, or peripheral), hospitalizations due to unstable angina pectoris or heart failure, all-cause mortality, diabetes in participants without baseline diabetes, new or recurrent cancers.
measure: Clinical and diagnostic significance of Dutch Lipid Clinic Network criteria and Simon Broome Registry criteria for diagnosis of FH in Russian population
time frame: up to 5 years
description: Clinical and diagnostic significance of Dutch Lipid Clinic Network criteria and Simon Broome Registry criteria for the diagnosis of FH in Russia.
measure: Family Health Team model and cascade testing in individuals with FH
time frame: up to 3 years
arm group label: Patients diagnosed with FH
description: Subjects of both sexes above the age of 18 with TC ≥7.5 mmol/L or LDL-C ≥4.9 mmol/L will be included in the Program. Clinical diagnosis of FH will be established using both the Dutch and the British criteria.
Those with secondary causes of hypercholesterolemia, such as untreated diabetes mellitus (HbA1c >8%) or hypothyroidism (thyroid-stimulating hormone >1.5 upper normal limit), renal failure (creatinine clearance <30 ml/min), holestatic liver diseases, including biliary cirrhosis, tumors with an active process in the last 5 years will be excluded from the study.
whole blood, serum, white cells, urine
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 7 Years
maximum age: 80 Years
healthy volunteers: No
last name: Valery Kukharchuk, MD, DMSc
role: Study Chair
affiliation: Russian Cardiology Research and Production Center
last name: Igor Sergienko, MD, DMSc
role: Study Director
affiliation: Russian Cardiology Research and Production Center
last name: Marat Ezhov, MD, DMSc
role: Principal Investigator
affiliation: Russian Cardiology Research and Production Center
last name: Marat Ezhov, MD, PhD
phone: +79104137499
email: Marat_Ezhov@mail.ru
last name: Igor Sergienko, MD, DMSc
phone: +79031492253
email: igorcardio@mail.ru
facility: 
status: Not yet recruiting
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country: Russian Federation
url: http://noatero.ru/ru/programma-noa
description: Program for identification of individuals at high and very high risk of cardiovascular complications
citation: M. S. Safarova, I. V. Sergienko, M. V. Ezhov, A. E. Semenova, M. A. Kachkovskiy, I. I. Shaposhnik, V. S. Gurevich, M. I. Voevoda, Y. P. Nikitin, V. V. Kuharchuk, Yu. A. Karpov Russian research program for early diagnosis and treatment of familial hypercholesterolaemia: Rationale and Design of the Russian FH Registry (RuFH). Journal of ATHEROSCLEROSIS AND DYSLIPIDAEMIAS 3: 7-15, 2014 (in Russian)
citation: Ezhov MV SI, Duplyakov DV, Abashina OE, Kachkovsky MA, Shaposhnik II, Genkel VV, Gurevich VS, Urazgildeeva SA, Tregubov AV, Konovalova TB, Muzalevskaya MV, Voevoda MI, Bazhan SS, Makarenkova KV, Timoshenko OV, Ragino YI, Urvantseva IA, Cozhocar KG, Sokolov AA, Boeva OI, Bolotova EV, Kushnaryova YB, Kuznetsova TY, Korneva VA, Bogdanov DY, Chichina EE, Soloviev VM, Smolenskaya OG, Galyavich AS, Safarova MS, Popova AV, Malakhov VV, Ansheles AA, Nozadze DN, Semenova AE, Rozhkova TA, Solovéva EY, Gornyakova NB, Karpov YA, Kukharchuk VV. Results of the Russian research program on the diagnosis and treatment of patients with familial hypercholesterolemia. High prevalence, low awareness, poor adherence. Atherosclerosis and Dyslipidaemias An official Journal of the Russian National Atherosclerosis Society (RNAS) 2017;2:5-15.
citation: EAS Familial Hypercholesterolaemia Studies Collaboration, Vallejo-Vaz AJ, Akram A, Kondapally Seshasai SR, Cole D, Watts GF, Hovingh GK, Kastelein JJ, Mata P, Raal FJ, Santos RD, Soran H, Freiberger T, Abifadel M, Aguilar-Salinas CA, Alnouri F, Alonso R, Al-Rasadi K, Banach M, Bogsrud MP, Bourbon M, Bruckert E, Car J, Ceska R, Corral P, Descamps O, Dieplinger H, Do CT, Durst R, Ezhov MV, Fras Z, Gaita D, Gaspar IM, Genest J, Harada-Shiba M, Jiang L, Kayikcioglu M, Lam CS, Latkovskis G, Laufs U, Liberopoulos E, Lin J, Lin N, Maher V, Majano N, Marais AD, März W, Mirrakhimov E, Miserez AR, Mitchenko O, Nawawi H, Nilsson L, Nordestgaard BG, Paragh G, Petrulioniene Z, Pojskic B, Reiner Ž, Sahebkar A, Santos LE, Schunkert H, Shehab A, Slimane MN, Stoll M, Su TC, Susekov A, Tilney M, Tomlinson B, Tselepis AD, Vohnout B, Widén E, Yamashita S, Catapano AL, Ray KK. Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes: Rationale and design of the global EAS Familial Hypercholesterolaemia Studies Collaboration. Atheroscler Suppl. 2016;22:1-32. doi: 10.1016/j.atherosclerosissup.2016.10.001.
responsible party type: Principal Investigator
investigator affiliation: Russian Cardiology Research and Production Center
investigator full name: Marat Vladislavovich Ezhov (MV Ezhov, MD, PhD, DMSc)
investigator title: Leading Researcher, MD, DMSc
mesh term: Hyperlipoproteinemia Type II
mesh term: Hypercholesterolemia