<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/NCT03775746</url>
  </required_header>
  <id_info>
    <org_study_id>RD2018-41</org_study_id>
    <nct_id>NCT03775746</nct_id>
  </id_info>
  <brief_title>Can Very Low Dose Rivaroxaban in Addition to Dual Antiplatelet Therapy (DAPT) Improve Thrombotic Status in Acute Coronray Syndrome (ACS) ACS</brief_title>
  <acronym>VaLiDate-R</acronym>
  <official_title>Can Very Low Dose Rivaroxaban in Addition to Dual Antiplatelet Therapy (DAPT) Improve Thrombotic Status in Acute Coronray Syndrome (ACS) ACS</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>East and North Hertfordshire NHS Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Hertfordshire</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>East and North Hertfordshire NHS Trust</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>
      A prospective, randomised, open label study of 3 clinically licensed treatments for ACS to&#xD;
      assess the effects of these treatments on blood tests of endogenous fibrinolysis. 50 patients&#xD;
      will be randomised to each of the 3 treatment arms in 1:1:1 ratio. Patients will receive the&#xD;
      randomised treatment for 1 month after their index admission with ACS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Heart attacks are caused by a blood clot occurring in a blood vessel (artery) which supplies&#xD;
      blood to the heart. Such a clot can build up and block the blood flow, depriving part of the&#xD;
      heart muscle of oxygen and blood, causing transient or permanent damage to the heart muscle.&#xD;
&#xD;
      The standard treatment for a heart attack is two blood thinning medications combined, every&#xD;
      day, to reduce the risk of further blood clots forming and to prevent another heart attack.&#xD;
      The highest risk of another heart attack is in the next 30 days after the first heart attack.&#xD;
&#xD;
      However, despite two blood thinners combined, some patients still go on to have another clot&#xD;
      (heart attack or stroke or death) and this can be life threatening. Earlier research has&#xD;
      shown that through a blood test, it is possible to identify patients who remain at increased&#xD;
      risk of further clots and who may benefit from further blood thinners to reduce the risk of&#xD;
      further heart attack, stroke and death in the next 30 days.&#xD;
&#xD;
      The aim of this study is to test which of 3 blood thinning treatment options (all already in&#xD;
      widespread clinical use) is best for patients to reduce further blood clots, in particular&#xD;
      the addition of low dose rivaroxaban.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 8, 2019</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The change in Lysis Time (LT) in the three treatment groups assessed using the GTT from admission to follow-up at 30 days</measure>
    <time_frame>30 days</time_frame>
    <description>To investigate, in patients with recent acute coronary syndrome and who have impaired endogenous fibrinolysis, whether the addition of low dose rivaroxaban to DAPT can improve endogenous thrombotic and fibrinolytic status</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Frequency of further angioplasty</measure>
    <time_frame>6 months</time_frame>
    <description>Clinical events including re-intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of further heart attack, stroke or death</measure>
    <time_frame>6 months</time_frame>
    <description>Incidence of further major adverse cardiac events</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Acute Coronary Syndrome</condition>
  <arm_group>
    <arm_group_label>Clopidogrel with Rivaroxaban</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Clopidogrel 75mg o.d. and Rivaroxaban 2.5mg b.i.d.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Clopidogrel</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Clopidogrel 75mg o.d.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ticagrelor</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ticagrelor 90mg b.i.d.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clopidogrel 75Mg Tablet</intervention_name>
    <description>Prevention of atherothrombotic events in percutaneous coronary intervention (adjunct with aspirin) in patients not already on clopidogrel</description>
    <arm_group_label>Clopidogrel</arm_group_label>
    <arm_group_label>Clopidogrel with Rivaroxaban</arm_group_label>
    <other_name>EU/1/08/465/001</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rivaroxaban 2.5Mg Tablet</intervention_name>
    <description>Prophylaxis of atherothrombotic events following an acute coronary syndrome with elevated cardiac biomarkers (in combination with aspirin alone or aspirin and clopidogrel)</description>
    <arm_group_label>Clopidogrel with Rivaroxaban</arm_group_label>
    <other_name>EU/1/08/472/025-035</other_name>
    <other_name>EU/1/08/472/041</other_name>
    <other_name>EU/1/08/472/046-047</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ticagrelor 90Mg Tablet</intervention_name>
    <description>Prevention of atherothrombotic events in patients with acute coronary syndrome [in combination with aspirin]</description>
    <arm_group_label>Ticagrelor</arm_group_label>
    <other_name>EU/1/10/655/007-011</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female patients aged 18 years or over&#xD;
&#xD;
          2. Have a diagnosis of acute coronary syndrome requiring treatment with dual antiplatelet&#xD;
             therapy&#xD;
&#xD;
          3. Be willing and able to understand the Participant Information Sheet and provide&#xD;
             informed consent&#xD;
&#xD;
          4. Agree to comply with the drawing of blood samples for the assessments&#xD;
&#xD;
          5. Not meet any of the exclusion criteria below&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Male and female participants aged &lt; 18 years of age.&#xD;
&#xD;
          2. Patient unwilling or unable to give informed consent&#xD;
&#xD;
          3. Patients who might be pregnant or are breast-feeding&#xD;
&#xD;
          4. Active clinically significant bleeding&#xD;
&#xD;
          5. Patient who, in the opinion of the investigator, has condition considered to be a&#xD;
             significant risk for major bleeding (such as current or recent gastrointestinal&#xD;
             ulceration, presence of malignant neoplasm at high risk of bleeding, recent brain or&#xD;
             spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial&#xD;
             haemorrhage, known or suspected oesophageal varices, arteriovenous malformations,&#xD;
             vascular aneurysms or major intraspinal or intracerebral vascular abnormalities)&#xD;
&#xD;
          6. Hepatic disease associated with coagulopathy and clinically relevant bleeding risk&#xD;
             including cirrhotic patients with Child Pugh B and C&#xD;
&#xD;
          7. Patient with any contraindications to use of antiplatelet agents or anticoagulants&#xD;
&#xD;
          8. Hypersensitivity to the active substance or to any of the excipients listed in section&#xD;
             6.1 of Summary of Product Characteristics (SmPC) of Rivaroxaban&#xD;
&#xD;
          9. Concomitant treatment with any other anticoagulants e.g. unfractionated heparin (UFH),&#xD;
             low molecular weight heparins (enoxaparin, dalteparin, etc.), heparin derivatives&#xD;
             (fondaparinux, etc.), oral anticoagulants (warfarin, dabigatran etexilate, apixaban&#xD;
             etc.) except under specific circumstances of switching anticoagulant therapy or when&#xD;
             UFH is given at doses necessary to maintain an open central venous or arterial&#xD;
             catheter&#xD;
&#xD;
         10. Concomitant treatment of ACS with antiplatelet therapy in patients with a prior stroke&#xD;
             or a transient ischaemic attack (TIA)&#xD;
&#xD;
         11. Patient with ongoing active alcohol or substance abuse or demonstrates signs or&#xD;
             clinical features of active substance abuse.&#xD;
&#xD;
         12. Patient with any major bleeding diathesis or blood dyscrasia at baseline (platelets&lt;70&#xD;
             x 109/l, Hb&lt;80 g/l, INR&gt;1.4, APTT&gt; x 2UNL, leucocyte count&lt; 3.5x 109/l, neutrophil&#xD;
             count&lt;1x 109/l)&#xD;
&#xD;
         13. Patient currently enrolled in an investigational drug trial&#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_contact>
    <last_name>Diana A Gorog, MD, PhD, FRCP</last_name>
    <phone>01438 284 753</phone>
    <email>d.gorog@nhs.net</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ying X Gue, MBChB, MRCP</last_name>
    <phone>01438 284 753</phone>
    <email>y.gue@nhs.net</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>East and North Hertfordshire NHS Trust</name>
      <address>
        <city>Stevenage</city>
        <state>Hertfordshire</state>
        <zip>SG1 4AB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Diana A Gorog</last_name>
      <phone>+44(0)1707 247512</phone>
      <email>d.gorog@nhs.net</email>
    </contact>
    <contact_backup>
      <last_name>Ying Gue</last_name>
      <phone>+44(0)1438 284753</phone>
      <email>y.gue@nhs.net</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>December 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 12, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 14, 2018</study_first_posted>
  <last_update_submitted>February 11, 2020</last_update_submitted>
  <last_update_submitted_qc>February 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acute Coronary Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rivaroxaban</mesh_term>
    <mesh_term>Clopidogrel</mesh_term>
    <mesh_term>Ticagrelor</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/NCT03775746
org study id: RD2018-41
nct id: NCT03775746
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A prospective, randomised, open label study of 3 clinically licensed treatments for ACS to
      assess the effects of these treatments on blood tests of endogenous fibrinolysis. 50 patients
      will be randomised to each of the 3 treatment arms in 1:1:1 ratio. Patients will receive the
      randomised treatment for 1 month after their index admission with ACS.
Heart attacks are caused by a blood clot occurring in a blood vessel (artery) which supplies
      blood to the heart. Such a clot can build up and block the blood flow, depriving part of the
      heart muscle of oxygen and blood, causing transient or permanent damage to the heart muscle.

      The standard treatment for a heart attack is two blood thinning medications combined, every
      day, to reduce the risk of further blood clots forming and to prevent another heart attack.
      The highest risk of another heart attack is in the next 30 days after the first heart attack.

      However, despite two blood thinners combined, some patients still go on to have another clot
      (heart attack or stroke or death) and this can be life threatening. Earlier research has
      shown that through a blood test, it is possible to identify patients who remain at increased
      risk of further clots and who may benefit from further blood thinners to reduce the risk of
      further heart attack, stroke and death in the next 30 days.

      The aim of this study is to test which of 3 blood thinning treatment options (all already in
      widespread clinical use) is best for patients to reduce further blood clots, in particular
      the addition of low dose rivaroxaban.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The change in Lysis Time (LT) in the three treatment groups assessed using the GTT from admission to follow-up at 30 days
time frame: 30 days
description: To investigate, in patients with recent acute coronary syndrome and who have impaired endogenous fibrinolysis, whether the addition of low dose rivaroxaban to DAPT can improve endogenous thrombotic and fibrinolytic status
measure: Frequency of further angioplasty
time frame: 6 months
description: Clinical events including re-intervention
measure: Frequency of further heart attack, stroke or death
time frame: 6 months
description: Incidence of further major adverse cardiac events
arm group label: Clopidogrel with Rivaroxaban
arm group type: Experimental
description: Clopidogrel 75mg o.d. and Rivaroxaban 2.5mg b.i.d.
arm group label: Clopidogrel
arm group type: Active Comparator
description: Clopidogrel 75mg o.d.
arm group label: Ticagrelor
arm group type: Active Comparator
description: Ticagrelor 90mg b.i.d.
intervention type: Drug
intervention name: Clopidogrel 75Mg Tablet
description: Prevention of atherothrombotic events in percutaneous coronary intervention (adjunct with aspirin) in patients not already on clopidogrel
arm group label: Clopidogrel
arm group label: Clopidogrel with Rivaroxaban
other name: EU/1/08/465/001
intervention type: Drug
intervention name: Rivaroxaban 2.5Mg Tablet
description: Prophylaxis of atherothrombotic events following an acute coronary syndrome with elevated cardiac biomarkers (in combination with aspirin alone or aspirin and clopidogrel)
arm group label: Clopidogrel with Rivaroxaban
other name: EU/1/08/472/025-035
other name: EU/1/08/472/041
other name: EU/1/08/472/046-047
intervention type: Drug
intervention name: Ticagrelor 90Mg Tablet
description: Prevention of atherothrombotic events in patients with acute coronary syndrome [in combination with aspirin]
arm group label: Ticagrelor
other name: EU/1/10/655/007-011
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Diana A Gorog, MD, PhD, FRCP
phone: 01438 284 753
email: d.gorog@nhs.net
last name: Ying X Gue, MBChB, MRCP
phone: 01438 284 753
email: y.gue@nhs.net
facility: 
status: Recruiting
contact: 
contact backup: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Acute Coronary Syndrome
mesh term: Syndrome
mesh term: Rivaroxaban
mesh term: Clopidogrel
mesh term: Ticagrelor
sharing ipd: No