<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/NCT03277001</url>
  </required_header>
  <id_info>
    <org_study_id>KY2017-279</org_study_id>
    <nct_id>NCT03277001</nct_id>
  </id_info>
  <brief_title>Study of Prophylactic Effect of Rivaroxaban on Venous Thromboembolism in AECOPD</brief_title>
  <acronym>SUPREME</acronym>
  <official_title>Multi-center、Randomize、Open、Non-inferiority Study of Prophylactic Effect of Rivaroxaban on Venous Thromboembolism in AECOPD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Huashan Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Huashan Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      AECOPD increases the risk of VTE.VTE prevention is a long way to go for high-risk VTE&#xD;
      patients in China.The incidence of AECOPD complicated with VTE in Asian population is high&#xD;
      and the mortality rate is high.Rivaroxaban, a new oral anticoagulant, has been widely used in&#xD;
      the treatment and prevention of VTE.However the question about the efficacy and safety of new&#xD;
      oral anticoagulant compared with LMWHs for the prevention of symptomatic VTE and VTE-related&#xD;
      death post-hospital discharge in high-risk AECOPD patients is still unknown. Thus this study&#xD;
      is to evaluate if the prophylactic anticoagulation effect by Rivaroxaban is non-inferiority&#xD;
      than Enoxaprine in high risk AECOPD and to evaluate the safety of using Rivaroxaban to&#xD;
      prevent VTE in high risk AECOPD comparing with Enoxaprine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The acute exacerbation of COPD increases the risk of venous thromboembolism.VTE prevention is&#xD;
      a long way to go for high-risk VTE patients in China.The incidence of AECOPD complicated with&#xD;
      VTE in Asian population is high and the mortality rate is high.Rivaroxaban, a new oral&#xD;
      anticoagulant, has been widely used in the treatment and prevention of VTE.However the&#xD;
      question about the efficacy and safety of new oral anticoagulant compared with LMWHs for the&#xD;
      prevention of symptomatic VTE and VTE-related death post-hospital discharge in high-risk&#xD;
      AECOPD patients is still unknown. Thus this study is to evaluate if the prophylactic&#xD;
      anticoagulation effect by Rivaroxaban is non-inferiority than Enoxaprine in high risk AECOPD&#xD;
      and to evaluate the safety of using Rivaroxaban to prevent VTE in high risk AECOPD comparing&#xD;
      with Enoxaprine.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">October 1, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2019</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>VTE incidence</measure>
    <time_frame>1 month</time_frame>
    <description>VTE incidence ( include PE and DVT)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>In-hospital Motality</measure>
    <time_frame>1 month</time_frame>
    <description>in-hospital Motality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital duration</measure>
    <time_frame>1 month</time_frame>
    <description>length of hospital stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>incidence of bleeding</measure>
    <time_frame>1 month</time_frame>
    <description>incidence of bleeding</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">438</enrollment>
  <condition>Acute Exacerbation Copd</condition>
  <condition>Venous Thromboembolism</condition>
  <arm_group>
    <arm_group_label>Enoxaparin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>AECOPD patients meeting the eligibility criterion by GOLD2017 in hospitalization Padua score &gt; 4</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Rivaroxaban</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AECOPD patients meeting the eligibility criterion by GOLD2017 in hospitalization Padua score &gt; 4</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rivaroxaban</intervention_name>
    <description>Rivaroxaban, po. 10mg/day（CrCl≥ 50 ml/min）or 5 mg /day (CrCl ≥ 30 and &lt; 50 ml/min) po.</description>
    <arm_group_label>Rivaroxaban</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enoxaparin</intervention_name>
    <description>Enoxaparin 40mg IH</description>
    <arm_group_label>Enoxaparin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  AECOPD patients meeting the eligibility criterion by GOLD2017 in hospitalization；Padua&#xD;
             score &gt; 4；Age from 40-80y&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients whose admitting diagnosis was VTE；Patients whose duration of hospital stay&#xD;
             was &lt;3 days or &gt;30 days ；Patients who received therapeutic doses of anticoagulants or&#xD;
             thrombolytic therapy for any indication before hospitalization；an organic lesion that&#xD;
             could bleed; severe liver or renal failure; confirmed or uncontrolled hypertension; a&#xD;
             congenital or acquired coagulation disorder; a history of hypersensitivity or&#xD;
             thrombocytopenia to heparins of any type；Patients who were contraindicated to&#xD;
             anticoagulant therapy, venography, or angiography&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shengqing Li, Ph D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Huashan Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Shengqing Li, Ph D</last_name>
    <phone>86-021-52887072</phone>
    <email>shengqingli@hotmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Yi Gong, Ph D</last_name>
    <phone>86-021-52887072</phone>
    <email>gongyi1978@hotmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Huashan hospital,Fudan university</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200040</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Aleva FE, Voets LWLM, Simons SO, de Mast Q, van der Ven AJAM, Heijdra YF. Prevalence and Localization of Pulmonary Embolism in Unexplained Acute Exacerbations of COPD: A Systematic Review and Meta-analysis. Chest. 2017 Mar;151(3):544-554. doi: 10.1016/j.chest.2016.07.034. Epub 2016 Aug 12.</citation>
    <PMID>27522956</PMID>
  </reference>
  <reference>
    <citation>Wang F, Cheng ZZ, Wang JL, Han WZ, Sun NN. [Incidence of pulmonary embolism in patients with acute exacerbations of chronic obstructive pulmonary disease: a meta-analysis]. Zhonghua Yi Xue Za Zhi. 2013 Jun 25;93(24):1868-71. Chinese.</citation>
    <PMID>24124736</PMID>
  </reference>
  <reference>
    <citation>Akpinar EE, Hosgun D, Akpinar S, Atac GK, Doganay B, Gulhan M. Incidence of pulmonary embolism during COPD exacerbation. J Bras Pneumol. 2014 Jan-Feb;40(1):38-45. doi: 10.1590/S1806-37132014000100006.</citation>
    <PMID>24626268</PMID>
  </reference>
  <reference>
    <citation>Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, Huisman M, King CS, Morris TA, Sood N, Stevens SM, Vintch JRE, Wells P, Woller SC, Moores L. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016 Feb;149(2):315-352. doi: 10.1016/j.chest.2015.11.026. Epub 2016 Jan 7. Erratum In: Chest. 2016 Oct;150(4):988.</citation>
    <PMID>26867832</PMID>
  </reference>
  <reference>
    <citation>Chen CY, Liao KM. The Incidence of Deep Vein Thrombosis in Asian Patients With Chronic Obstructive Pulmonary Disease. Medicine (Baltimore). 2015 Nov;94(44):e1741. doi: 10.1097/MD.0000000000001741.</citation>
    <PMID>26554770</PMID>
  </reference>
  <reference>
    <citation>EINSTEIN-PE Investigators; Buller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5;366(14):1287-97. doi: 10.1056/NEJMoa1113572. Epub 2012 Mar 26.</citation>
    <PMID>22449293</PMID>
  </reference>
  <reference>
    <citation>Ageno W, Mantovani LG, Haas S, Kreutz R, Haupt V, Schneider J, Turpie AG. XALIA: rationale and design of a non-interventional study of rivaroxaban compared with standard therapy for initial and long-term anticoagulation in deep vein thrombosis. Thromb J. 2014 Jul 14;12:16. doi: 10.1186/1477-9560-12-16. eCollection 2014.</citation>
    <PMID>25093014</PMID>
  </reference>
  <reference>
    <citation>Cohen AT, Spiro TE, Buller HR, Haskell L, Hu D, Hull R, Mebazaa A, Merli G, Schellong S, Spyropoulos AC, Tapson V; MAGELLAN Investigators. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013 Feb 7;368(6):513-23. doi: 10.1056/NEJMoa1111096.</citation>
    <PMID>23388003</PMID>
  </reference>
  <reference>
    <citation>Duran A, Sengupta N, Diamantopoulos A, Forster F, Kwong L, Lees M. Cost and outcomes associated with rivaroxaban vs enoxaparin for the prevention of postsurgical venous thromboembolism from a US payer's perspective. J Med Econ. 2011;14(6):824-34. doi: 10.3111/13696998.2011.623203. Epub 2011 Oct 24.</citation>
    <PMID>22023098</PMID>
  </reference>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>September 2, 2017</study_first_submitted>
  <study_first_submitted_qc>September 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 8, 2017</study_first_posted>
  <last_update_submitted>September 6, 2017</last_update_submitted>
  <last_update_submitted_qc>September 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 8, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Huashan Hospital</investigator_affiliation>
    <investigator_full_name>Shengqing Li</investigator_full_name>
    <investigator_title>Chief physician, Professor-levelled doctor</investigator_title>
  </responsible_party>
  <keyword>AECOPD</keyword>
  <keyword>VTE prevention</keyword>
  <keyword>Rivaroxaban</keyword>
  <keyword>LMWHs</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thromboembolism</mesh_term>
    <mesh_term>Venous Thromboembolism</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Enoxaparin</mesh_term>
    <mesh_term>Rivaroxaban</mesh_term>
  </intervention_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/NCT03277001
org study id: KY2017-279
nct id: NCT03277001
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
AECOPD increases the risk of VTE.VTE prevention is a long way to go for high-risk VTE
      patients in China.The incidence of AECOPD complicated with VTE in Asian population is high
      and the mortality rate is high.Rivaroxaban, a new oral anticoagulant, has been widely used in
      the treatment and prevention of VTE.However the question about the efficacy and safety of new
      oral anticoagulant compared with LMWHs for the prevention of symptomatic VTE and VTE-related
      death post-hospital discharge in high-risk AECOPD patients is still unknown. Thus this study
      is to evaluate if the prophylactic anticoagulation effect by Rivaroxaban is non-inferiority
      than Enoxaprine in high risk AECOPD and to evaluate the safety of using Rivaroxaban to
      prevent VTE in high risk AECOPD comparing with Enoxaprine.
The acute exacerbation of COPD increases the risk of venous thromboembolism.VTE prevention is
      a long way to go for high-risk VTE patients in China.The incidence of AECOPD complicated with
      VTE in Asian population is high and the mortality rate is high.Rivaroxaban, a new oral
      anticoagulant, has been widely used in the treatment and prevention of VTE.However the
      question about the efficacy and safety of new oral anticoagulant compared with LMWHs for the
      prevention of symptomatic VTE and VTE-related death post-hospital discharge in high-risk
      AECOPD patients is still unknown. Thus this study is to evaluate if the prophylactic
      anticoagulation effect by Rivaroxaban is non-inferiority than Enoxaprine in high risk AECOPD
      and to evaluate the safety of using Rivaroxaban to prevent VTE in high risk AECOPD comparing
      with Enoxaprine.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: VTE incidence
time frame: 1 month
description: VTE incidence ( include PE and DVT)
measure: In-hospital Motality
time frame: 1 month
description: in-hospital Motality
measure: Hospital duration
time frame: 1 month
description: length of hospital stay
measure: incidence of bleeding
time frame: 1 month
description: incidence of bleeding
arm group label: Enoxaparin
arm group type: Active Comparator
description: AECOPD patients meeting the eligibility criterion by GOLD2017 in hospitalization Padua score > 4
arm group label: Rivaroxaban
arm group type: Experimental
description: AECOPD patients meeting the eligibility criterion by GOLD2017 in hospitalization Padua score > 4
intervention type: Drug
intervention name: Rivaroxaban
description: Rivaroxaban, po. 10mg/day（CrCl≥ 50 ml/min）or 5 mg /day (CrCl ≥ 30 and < 50 ml/min) po.
arm group label: Rivaroxaban
intervention type: Drug
intervention name: Enoxaparin
description: Enoxaparin 40mg IH
arm group label: Enoxaparin
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Shengqing Li, Ph D
role: Principal Investigator
affiliation: Huashan Hospital
last name: Shengqing Li, Ph D
phone: 86-021-52887072
email: shengqingli@hotmail.com
last name: Yi Gong, Ph D
phone: 86-021-52887072
email: gongyi1978@hotmail.com
facility: 
country: China
citation: Aleva FE, Voets LWLM, Simons SO, de Mast Q, van der Ven AJAM, Heijdra YF. Prevalence and Localization of Pulmonary Embolism in Unexplained Acute Exacerbations of COPD: A Systematic Review and Meta-analysis. Chest. 2017 Mar;151(3):544-554. doi: 10.1016/j.chest.2016.07.034. Epub 2016 Aug 12.
PMID: 27522956
citation: Wang F, Cheng ZZ, Wang JL, Han WZ, Sun NN. [Incidence of pulmonary embolism in patients with acute exacerbations of chronic obstructive pulmonary disease: a meta-analysis]. Zhonghua Yi Xue Za Zhi. 2013 Jun 25;93(24):1868-71. Chinese.
PMID: 24124736
citation: Akpinar EE, Hosgun D, Akpinar S, Atac GK, Doganay B, Gulhan M. Incidence of pulmonary embolism during COPD exacerbation. J Bras Pneumol. 2014 Jan-Feb;40(1):38-45. doi: 10.1590/S1806-37132014000100006.
PMID: 24626268
citation: Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, Huisman M, King CS, Morris TA, Sood N, Stevens SM, Vintch JRE, Wells P, Woller SC, Moores L. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016 Feb;149(2):315-352. doi: 10.1016/j.chest.2015.11.026. Epub 2016 Jan 7. Erratum In: Chest. 2016 Oct;150(4):988.
PMID: 26867832
citation: Chen CY, Liao KM. The Incidence of Deep Vein Thrombosis in Asian Patients With Chronic Obstructive Pulmonary Disease. Medicine (Baltimore). 2015 Nov;94(44):e1741. doi: 10.1097/MD.0000000000001741.
PMID: 26554770
citation: EINSTEIN-PE Investigators; Buller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5;366(14):1287-97. doi: 10.1056/NEJMoa1113572. Epub 2012 Mar 26.
PMID: 22449293
citation: Ageno W, Mantovani LG, Haas S, Kreutz R, Haupt V, Schneider J, Turpie AG. XALIA: rationale and design of a non-interventional study of rivaroxaban compared with standard therapy for initial and long-term anticoagulation in deep vein thrombosis. Thromb J. 2014 Jul 14;12:16. doi: 10.1186/1477-9560-12-16. eCollection 2014.
PMID: 25093014
citation: Cohen AT, Spiro TE, Buller HR, Haskell L, Hu D, Hull R, Mebazaa A, Merli G, Schellong S, Spyropoulos AC, Tapson V; MAGELLAN Investigators. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013 Feb 7;368(6):513-23. doi: 10.1056/NEJMoa1111096.
PMID: 23388003
citation: Duran A, Sengupta N, Diamantopoulos A, Forster F, Kwong L, Lees M. Cost and outcomes associated with rivaroxaban vs enoxaparin for the prevention of postsurgical venous thromboembolism from a US payer's perspective. J Med Econ. 2011;14(6):824-34. doi: 10.3111/13696998.2011.623203. Epub 2011 Oct 24.
PMID: 22023098
responsible party type: Principal Investigator
investigator affiliation: Huashan Hospital
investigator full name: Shengqing Li
investigator title: Chief physician, Professor-levelled doctor
mesh term: Thromboembolism
mesh term: Venous Thromboembolism
mesh term: Enoxaparin
mesh term: Rivaroxaban