<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/NCT03820466</url>
  </required_header>
  <id_info>
    <org_study_id>GRAY-ZONE</org_study_id>
    <nct_id>NCT03820466</nct_id>
  </id_info>
  <brief_title>Effect of Platelet Inhibition and / or Lipid Lowering in Non-ACS-patients With Positive Troponin</brief_title>
  <acronym>GRAY-ZONE</acronym>
  <official_title>Investigator-initiated, Placebo-controlled, Randomized Trial to Assess the Efficacy and Safety of Platelet Inhibition and/ or Lipid Lowering in Non-ACS-patients With Elevated High-sensitivity Troponin Values</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dr. med. Mahir Karakas</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universitätsklinikum Hamburg-Eppendorf</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>
      The study evaluates the effect of platelet inhibition and / or lipid lowering in&#xD;
      non-ACS-patients with symptoms suggestive for ACS, and elevated high-sensitivity troponin&#xD;
      values&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Current databases show, that high-/ ultra sensitive (hs)/ (us) troponin levels above the 99th&#xD;
      percentile in patients presenting with chest pain are indicative for future cardiovascular&#xD;
      events, even when acute coronary syndrome (ACS) was ruled out. Most of these non-ACS-patients&#xD;
      are discharged without specific/ preventive therapy (anti-platelet or anti-lipid), although&#xD;
      &quot;positive&quot; troponin values (any value at any time during hospitalisation above the 99th&#xD;
      percentile) seem to clearly indicate underlying myocardial ischemia. In summary, there is an&#xD;
      unmet need and huge potential to reduce mortality and morbidity in Chest Pain Unit patients&#xD;
      by specific therapy. The investigators propose that platelet inhibition by Aspirin or lipid&#xD;
      lowering by Atorvastatin will prevent plaque rupture and superimposition of thrombosis to&#xD;
      coronary atherosclerosis in this population. It is planned to conduct a controlled clinical&#xD;
      trial: 3,000 troponin positive patients presenting at emergency room (ER)/ CPU with symptoms&#xD;
      suggestive for ACS, but an ACS was ruled out, will be assigned randomly to Aspirin 100 mg&#xD;
      and/ or Atorvastatin 20 mg versus placebo (2x2 factorial design).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    insufficient recruitment due to the pandemic situation&#xD;
  </why_stopped>
  <start_date type="Actual">February 21, 2020</start_date>
  <completion_date type="Actual">April 7, 2022</completion_date>
  <primary_completion_date type="Actual">December 2, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Myocardial infarction and/ or cardiovascular death and/ or revascularization</measure>
    <time_frame>Until last patient has completed 12 months of follow-up</time_frame>
    <description>Time to myocardial infarction, coronary revascularization, or death, whatever comes first</description>
  </primary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">68</enrollment>
  <condition>Acute Chest Syndrome</condition>
  <arm_group>
    <arm_group_label>Aspirin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Aspirin 100 mg once daily and Placebo Atorvastatin once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Atorvastatin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Atorvastatin 20 mg once daily and Placebo Aspirin once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aspirin-Atorvastatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Aspirin 100 mg once daily and Atorvastatin 20 mg once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo Aspirin once daily and Placebo Atorvastatin once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aspirin</intervention_name>
    <description>Once daily application of platelet inhibiting medication</description>
    <arm_group_label>Aspirin</arm_group_label>
    <arm_group_label>Aspirin-Atorvastatin</arm_group_label>
    <other_name>Acetyl Salicyl Acid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atorvastatin</intervention_name>
    <description>Once daily application of lipid lowering medication</description>
    <arm_group_label>Aspirin-Atorvastatin</arm_group_label>
    <arm_group_label>Atorvastatin</arm_group_label>
    <other_name>Statin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Aspirin</intervention_name>
    <description>Once daily application of placebo</description>
    <arm_group_label>Atorvastatin</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Placebo Oral Tablet</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Atorvastatin</intervention_name>
    <description>Once daily application of placebo</description>
    <arm_group_label>Aspirin</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Placebo Oral Tablet</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient with symptoms suggestive for ACS presenting within 48 hours after onset in the&#xD;
             ER/ Chest Pain Unit (CPU)&#xD;
&#xD;
          -  Patient has at least one elevated high-sensitivity troponin I or T value&#xD;
&#xD;
          -  Chest pain is classified as non-ACS, despite elevated hsTn (e.g. because of missing&#xD;
             troponin dynamics)&#xD;
&#xD;
          -  At least 50 years of age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Indication for antiplatelet therapy (e.g transient ischemic attack, or stable coronary&#xD;
             artery diseases -CAD) or anticoagulation therapy (such as atrial fibrillation)&#xD;
&#xD;
          -  Indication for anti-lipid therapy&#xD;
&#xD;
          -  Any evidence of an acute myocardial necrosis (e.g imaging evidence of new regional&#xD;
             wall motion abnormality, or significant ST-segment-T wave (ST-T) changes in ECG)&#xD;
&#xD;
          -  Untreated clinically significant CAD requiring revascularization&#xD;
&#xD;
          -  Hemoglobin value below 8 mg/d, and/or creatinine kinase ≥3 times ULN, and/or AST or&#xD;
             ALT ≥3 times ULN&#xD;
&#xD;
          -  Active malignancy of any organ system, treated or untreated. Subjects have to be in&#xD;
             remission for at least 36 months to be eligible.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mahir Karakas, MD</last_name>
    <role>Study Chair</role>
    <affiliation>University Heart Center Hamburg</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Berlin, Campus Benjamin-Franklin</name>
      <address>
        <city>Berlin</city>
        <zip>12203</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asklepios Harz-Hospital Goslar</name>
      <address>
        <city>Goslar</city>
        <zip>38642</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Heart Center Hamburg</name>
      <address>
        <city>Hamburg</city>
        <zip>20246</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Heidelberg</name>
      <address>
        <city>Heidelberg</city>
        <zip>69120</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Leipzig</name>
      <address>
        <city>Leipzig</city>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Robert-Bosch-Hospital Stuttgart</name>
      <address>
        <city>Stuttgart</city>
        <zip>70376</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Ulm</name>
      <address>
        <city>Ulm</city>
        <zip>89081</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>October 2, 2017</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>May 17, 2022</last_update_submitted>
  <last_update_submitted_qc>May 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Universitätsklinikum Hamburg-Eppendorf</investigator_affiliation>
    <investigator_full_name>Dr. med. Mahir Karakas</investigator_full_name>
    <investigator_title>Coordinating Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Aspirin</keyword>
  <keyword>Atorvastatin</keyword>
  <keyword>Troponin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acute Chest Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Atorvastatin</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/NCT03820466
org study id: GRAY-ZONE
nct id: NCT03820466
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The study evaluates the effect of platelet inhibition and / or lipid lowering in
      non-ACS-patients with symptoms suggestive for ACS, and elevated high-sensitivity troponin
      values
Current databases show, that high-/ ultra sensitive (hs)/ (us) troponin levels above the 99th
      percentile in patients presenting with chest pain are indicative for future cardiovascular
      events, even when acute coronary syndrome (ACS) was ruled out. Most of these non-ACS-patients
      are discharged without specific/ preventive therapy (anti-platelet or anti-lipid), although
      "positive" troponin values (any value at any time during hospitalisation above the 99th
      percentile) seem to clearly indicate underlying myocardial ischemia. In summary, there is an
      unmet need and huge potential to reduce mortality and morbidity in Chest Pain Unit patients
      by specific therapy. The investigators propose that platelet inhibition by Aspirin or lipid
      lowering by Atorvastatin will prevent plaque rupture and superimposition of thrombosis to
      coronary atherosclerosis in this population. It is planned to conduct a controlled clinical
      trial: 3,000 troponin positive patients presenting at emergency room (ER)/ CPU with symptoms
      suggestive for ACS, but an ACS was ruled out, will be assigned randomly to Aspirin 100 mg
      and/ or Atorvastatin 20 mg versus placebo (2x2 factorial design).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Care Provider, Outcomes Assessor)
measure: Myocardial infarction and/ or cardiovascular death and/ or revascularization
time frame: Until last patient has completed 12 months of follow-up
description: Time to myocardial infarction, coronary revascularization, or death, whatever comes first
arm group label: Aspirin
arm group type: Active Comparator
description: Aspirin 100 mg once daily and Placebo Atorvastatin once daily
arm group label: Atorvastatin
arm group type: Active Comparator
description: Atorvastatin 20 mg once daily and Placebo Aspirin once daily
arm group label: Aspirin-Atorvastatin
arm group type: Experimental
description: Aspirin 100 mg once daily and Atorvastatin 20 mg once daily
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo Aspirin once daily and Placebo Atorvastatin once daily
intervention type: Drug
intervention name: Aspirin
description: Once daily application of platelet inhibiting medication
arm group label: Aspirin
arm group label: Aspirin-Atorvastatin
other name: Acetyl Salicyl Acid
intervention type: Drug
intervention name: Atorvastatin
description: Once daily application of lipid lowering medication
arm group label: Aspirin-Atorvastatin
arm group label: Atorvastatin
other name: Statin
intervention type: Drug
intervention name: Placebo Aspirin
description: Once daily application of placebo
arm group label: Atorvastatin
arm group label: Placebo
other name: Placebo Oral Tablet
intervention type: Drug
intervention name: Placebo Atorvastatin
description: Once daily application of placebo
arm group label: Aspirin
arm group label: Placebo
other name: Placebo Oral Tablet
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Mahir Karakas, MD
role: Study Chair
affiliation: University Heart Center Hamburg
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
responsible party type: Sponsor-Investigator
investigator affiliation: Universitätsklinikum Hamburg-Eppendorf
investigator full name: Dr. med. Mahir Karakas
investigator title: Coordinating Principal Investigator
mesh term: Acute Chest Syndrome
mesh term: Aspirin
mesh term: Atorvastatin
sharing ipd: No