<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/NCT03789695</url>
  </required_header>
  <id_info>
    <org_study_id>1160.283</org_study_id>
    <nct_id>NCT03789695</nct_id>
  </id_info>
  <brief_title>RE-ELECT. Dabigatran vs Warfarin in AF Patients With T2DM and CKD</brief_title>
  <acronym>RE-ELECT</acronym>
  <official_title>RE-ELECT Study: &quot;Randomized Evaluation of Changing Kidney Function Over a Time in Patients With Atrial Fibrillation (AF), Concomitant T2DM and Existing Chronic Kidney Disease (CKD) Treated With Dabigatran or Warfarin for Stroke Prevention&quot;</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Irina Ermolaeva</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>I.M. Sechenov First Moscow State Medical University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Kidney function in patients with atrial fibrillation (AF) is tending to decline over a time&#xD;
      which is clearly demonstrated in clinical studies. Renal impairment is a risk factor for&#xD;
      stroke, its progression is associated with unfavorable prognosis. So preserving kidney&#xD;
      function should be considered as a one of priorities when choosing treatment strategies which&#xD;
      is especially important in patients with existing chronic kidney disease (CKD) or in patients&#xD;
      who have risk of its development. This is especially relevant for the patients with type 2&#xD;
      diabetes mellitus (T2DM) and with CKD who can be considered as a group of risk for rapid&#xD;
      kidney function decline.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It is suggested that the decline in renal function may occur more slowly in patients&#xD;
      receiving dabigatran etexilate (Pradaxa) compared to patients taking warfarin. The planned&#xD;
      trial is a prospective phase IV randomized trial in which patients with AF, T2DM and CKD will&#xD;
      be randomized to groups receiving either dabigatran etexilate (Pradaxa) or warfarin. The main&#xD;
      goal of the study is to assess the differences in annual eGFR reduction between patients&#xD;
      receiving dabigatran etexilate (Pradaxa) or warfarin for 24 months. The difference in annual&#xD;
      eGFR reduction will be estimated using the SMPI parameters (mixed model of repeated&#xD;
      measurements). Secondary goals are as follows: - to evaluate the progression of albuminuria&#xD;
      during treatment with dabigatran etexilate (Pradaxa) or warfarin based on the combined&#xD;
      endpoint; - to evaluate the dynamics of the albumin/creatinine ratio (ACR) in urine during 2&#xD;
      years of treatment with dabigatran etexilate (Pradaxa) or warfarin; - to evaluate bleeding&#xD;
      episodes, acute cerebrovascular accident, and systemic embolism in the dabigatran etexilate&#xD;
      (Pradaxa) and warfarin groups; - to compare glycemic control (HbA1c) in patients receiving&#xD;
      dabigatran etexilate (Pradaxa) and warfarin&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 14, 2018</start_date>
  <completion_date type="Anticipated">May 2022</completion_date>
  <primary_completion_date type="Anticipated">July 2021</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>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Difference in annual eGFR decline (slopes) between dabigatran and warfarin patients</measure>
    <time_frame>2 years</time_frame>
    <description>eGFR is to be calculated with CKD-EPI equation at baseline and at subsequent major visits.&#xD;
for primary analysis only eGFR levels at one year and second year of treatment will be used. In case of one of values required for the analysis is missed LOCF (last observational carried forward) approach will be used</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Atrial Fibrillation</condition>
  <condition>T2DM (Type 2 Diabetes Mellitus)</condition>
  <condition>Chronic Kidney Diseases</condition>
  <arm_group>
    <arm_group_label>Dabigatran etexilate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dabigatran etexilate (Pradaxa) 110 mg b.i.d. or 150 mg b.i.d. according SmPC during 2 years</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Warfarin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Warfarin under the control of INR once a month (target range 2.0 - 3.0) during 2 years</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dabigatran Etexilate</intervention_name>
    <description>Study drug dabigatran etexilate. There are two dosage regimens of dabigatran etexilate used in the study: 150 mg b.i.d. and 110 mg b.i.d. The dose of dabigatran etexilate will be chosen by the investigator in accordance with Russian PRADAXA SmPC</description>
    <arm_group_label>Dabigatran etexilate</arm_group_label>
    <arm_group_label>Warfarin</arm_group_label>
    <other_name>Pradaxa</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Non-valvular atrial fibrillation&#xD;
&#xD;
          -  Diagnosis of T2D according to Russian Clinical Guidelines&#xD;
&#xD;
          -  Chronic kidney disease according to KDIGO definition*&#xD;
&#xD;
          -  Stable RAS background treatment&#xD;
&#xD;
          -  Age &gt; 18 yrs;&#xD;
&#xD;
          -  Informed consent to participate in the study signed by the patient.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  HbA1c &gt;10%&#xD;
&#xD;
          -  UACR &gt; 3000&#xD;
&#xD;
          -  Renal transplant&#xD;
&#xD;
          -  Biopsy proven kidney entities other than Diabetic Kidney Disease (if known only, no&#xD;
             kidney biopsy is planned within the study)&#xD;
&#xD;
          -  Background immunosuppressant therapy&#xD;
&#xD;
          -  Hematologic disorders which can influence hemostasis (hemoblastosis, etc.); connective&#xD;
             tissue diseases (SLE, systemic scleroderma, dermatomyositis) and any vasculitis;&#xD;
&#xD;
          -  Primary or secondary antiphospholipid syndrome;&#xD;
&#xD;
          -  Known cancer diagnosis;&#xD;
&#xD;
          -  Major surgical interventions within 3 months before the study enrollment and planned&#xD;
             for the timelines of the study;&#xD;
&#xD;
          -  Clinically relevant bleeding events within 3 months before the study enrollment;&#xD;
&#xD;
          -  Acute coronary syndrome, PCI or CABG within 12 months before the study enrollment;&#xD;
&#xD;
          -  Hemorrhagic stroke within 12 months before the study enrollment;&#xD;
&#xD;
          -  Organ damages resulted from clinically relevant bleeding within 6 months before&#xD;
             randomization&#xD;
&#xD;
          -  Major trauma or any craniocerebral trauma within 30 days before randomization&#xD;
&#xD;
          -  Uncontrolled hypertension (systolic BP&gt;180 and or diastolic BP&gt;100 while on&#xD;
             antihypertensive treatment)&#xD;
&#xD;
          -  CHF III-IV functional class (by NYHA)&#xD;
&#xD;
          -  Ischemic stroke within the last 14 days before randomization&#xD;
&#xD;
          -  Concomitant aspirin and/or clopidogrel use;&#xD;
&#xD;
          -  Persistent use of drugs with potential nephrotoxic effects (NSAIDs, cytotoxic drugs&#xD;
             etc.);&#xD;
&#xD;
          -  Need in anticoagulation treatment for disease other than AF&#xD;
&#xD;
          -  Pregnancy and lactation;&#xD;
&#xD;
          -  Creatinine clearance &lt; 30 ml/min (by Cockroft - Gault equation)&#xD;
&#xD;
          -  Thrombocytopenia of &lt;100 *109 /л&#xD;
&#xD;
          -  Hepatic failure B and C by Child-Pugh score&#xD;
&#xD;
          -  Psychiatrist disorders&#xD;
&#xD;
          -  Background poor compliance&#xD;
&#xD;
          -  Known hypersensitivity to dabigatran, warfarin or their components&#xD;
&#xD;
          -  Life expectancy less than two years&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dmitry Napalkov</last_name>
    <role>Principal Investigator</role>
    <affiliation>First Moscow State Medical University (Sechenov's University)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Dmitry Napalkov</last_name>
    <phone>+79104520841</phone>
    <email>dminap@mail.ru</email>
  </overall_contact>
  <location>
    <facility>
      <name>I.M.Sechenov First Moscow State Medical University (Sechenov University)</name>
      <address>
        <city>Moscow</city>
        <zip>119991</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dmitry Napalkov</last_name>
      <phone>+79104520841</phone>
      <email>dminap@mail.ru</email>
    </contact>
    <contact_backup>
      <last_name>Anastasia Sokolova</last_name>
      <phone>+79036135898</phone>
      <email>sokolovastasya2@gmail.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>December 27, 2018</study_first_submitted>
  <study_first_submitted_qc>December 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 31, 2018</study_first_posted>
  <last_update_submitted>March 23, 2021</last_update_submitted>
  <last_update_submitted_qc>March 23, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 26, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>I.M. Sechenov First Moscow State Medical University</investigator_affiliation>
    <investigator_full_name>Irina Ermolaeva</investigator_full_name>
    <investigator_title>Head of Department of preclinical and clinical trials management</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dabigatran</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03789695
org study id: 1160.283
nct id: NCT03789695
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Kidney function in patients with atrial fibrillation (AF) is tending to decline over a time
      which is clearly demonstrated in clinical studies. Renal impairment is a risk factor for
      stroke, its progression is associated with unfavorable prognosis. So preserving kidney
      function should be considered as a one of priorities when choosing treatment strategies which
      is especially important in patients with existing chronic kidney disease (CKD) or in patients
      who have risk of its development. This is especially relevant for the patients with type 2
      diabetes mellitus (T2DM) and with CKD who can be considered as a group of risk for rapid
      kidney function decline.
It is suggested that the decline in renal function may occur more slowly in patients
      receiving dabigatran etexilate (Pradaxa) compared to patients taking warfarin. The planned
      trial is a prospective phase IV randomized trial in which patients with AF, T2DM and CKD will
      be randomized to groups receiving either dabigatran etexilate (Pradaxa) or warfarin. The main
      goal of the study is to assess the differences in annual eGFR reduction between patients
      receiving dabigatran etexilate (Pradaxa) or warfarin for 24 months. The difference in annual
      eGFR reduction will be estimated using the SMPI parameters (mixed model of repeated
      measurements). Secondary goals are as follows: - to evaluate the progression of albuminuria
      during treatment with dabigatran etexilate (Pradaxa) or warfarin based on the combined
      endpoint; - to evaluate the dynamics of the albumin/creatinine ratio (ACR) in urine during 2
      years of treatment with dabigatran etexilate (Pradaxa) or warfarin; - to evaluate bleeding
      episodes, acute cerebrovascular accident, and systemic embolism in the dabigatran etexilate
      (Pradaxa) and warfarin groups; - to compare glycemic control (HbA1c) in patients receiving
      dabigatran etexilate (Pradaxa) and warfarin
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Difference in annual eGFR decline (slopes) between dabigatran and warfarin patients
time frame: 2 years
description: eGFR is to be calculated with CKD-EPI equation at baseline and at subsequent major visits.
for primary analysis only eGFR levels at one year and second year of treatment will be used. In case of one of values required for the analysis is missed LOCF (last observational carried forward) approach will be used
arm group label: Dabigatran etexilate
arm group type: Experimental
description: Dabigatran etexilate (Pradaxa) 110 mg b.i.d. or 150 mg b.i.d. according SmPC during 2 years
arm group label: Warfarin
arm group type: Active Comparator
description: Warfarin under the control of INR once a month (target range 2.0 - 3.0) during 2 years
intervention type: Drug
intervention name: Dabigatran Etexilate
description: Study drug dabigatran etexilate. There are two dosage regimens of dabigatran etexilate used in the study: 150 mg b.i.d. and 110 mg b.i.d. The dose of dabigatran etexilate will be chosen by the investigator in accordance with Russian PRADAXA SmPC
arm group label: Dabigatran etexilate
arm group label: Warfarin
other name: Pradaxa
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dmitry Napalkov
role: Principal Investigator
affiliation: First Moscow State Medical University (Sechenov's University)
last name: Dmitry Napalkov
phone: +79104520841
email: dminap@mail.ru
facility: 
status: Recruiting
contact: 
contact backup: 
country: Russian Federation
responsible party type: Sponsor-Investigator
investigator affiliation: I.M. Sechenov First Moscow State Medical University
investigator full name: Irina Ermolaeva
investigator title: Head of Department of preclinical and clinical trials management
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Atrial Fibrillation
mesh term: Diabetes Mellitus, Type 2
mesh term: Dabigatran
sharing ipd: No