<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/NCT03819894</url>
  </required_header>
  <id_info>
    <org_study_id>H18-02116</org_study_id>
    <nct_id>NCT03819894</nct_id>
  </id_info>
  <brief_title>Hs-cTn - Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women</brief_title>
  <acronym>CODE-MI</acronym>
  <official_title>Hs-cTn - Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BC Centre for Improved Cardiovascular Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Canadian Institutes of Health Research (CIHR)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>BC Centre for Improved Cardiovascular Health</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 project is focussed on evaluating the impact of using a female-specific threshold in the&#xD;
      diagnosis of myocardial infarction. This female threshold is lower than the overall hs-cTn&#xD;
      threshold currently in use. The investigators hypothesize that this change in process,&#xD;
      applied at the hospital level, will lead to better assessment, treatment and outcomes of&#xD;
      women presenting to the emergency department with chest pain that is cardiac in nature.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In subjects with suspected acute coronary syndromes (ACS), females are significantly less&#xD;
      likely to undergo investigations, receive evidence-based treatments, and consistently have&#xD;
      worse outcomes than males. The gap in outcomes is particularly marked among adults &lt; 55 years&#xD;
      of age. Sex differences in symptom presentation and in the diagnostic threshold for cardiac&#xD;
      biomarkers have been suggested as reasons for the under-diagnosis and under-treatment of&#xD;
      women. Cardiac troponin (cTn) T and I are proteins specific to the myocardium, which with&#xD;
      elevated and changing concentrations detected in the blood, along with signs or symptoms&#xD;
      consistent with myocardial ischemia, are indicative of a diagnosis of myocardial infarction&#xD;
      (MI). With the introduction of high-sensitivity (hs) cTn tests, which allow the detection of&#xD;
      very low concentrations of troponin, it has become evident that the level of cTn in a healthy&#xD;
      population is approximately two-fold higher in males than in females.&#xD;
&#xD;
      Consequently, the 99th percentile threshold for cTn, the reference value used in diagnosis of&#xD;
      MI, is lower in females compared to males. Despite this evidence and recent guidelines&#xD;
      recommending the use of sex specific thresholds, a single, overall cTn threshold is still&#xD;
      being used for diagnosis of MI, in both men and women, in most clinical settings.&#xD;
&#xD;
      There is mounting evidence from several jurisdictions that the rate of MI is increasing among&#xD;
      younger females, and that there is a persistent under-diagnosis, under-treatment, and high&#xD;
      risk of adverse outcomes among females, especially younger females, compared to their male&#xD;
      counterparts. A better approach to the diagnostic assessment of females presenting to the&#xD;
      emergency department (ED) with chest pain is therefore urgently needed. Additionally, several&#xD;
      Canadian hospitals have recently made the transition from sensitive to high sensitivity cTn&#xD;
      assays, allowing for the examination of subtle but important sex-specific differences in cTn&#xD;
      concentrations. With this background, the investigators propose a nationwide, randomized&#xD;
      clinical trial (RCT) to determine whether establishing female thresholds results in improved&#xD;
      diagnosis and treatment of MI and therefore improved prognosis in women.&#xD;
&#xD;
      To determine whether the use of female hs-cTn thresholds in the assessment of women&#xD;
      presenting to the ED with chest pain suggestive of cardiac ischemia, improves diagnostic&#xD;
      assessment, treatment and 1-year outcomes. Specifically, the investigators will examine the&#xD;
      impact of using female hs-cTn thresholds on:&#xD;
&#xD;
        -  Diagnostic and therapeutic strategies;&#xD;
&#xD;
        -  Prognosis: 1-year all-cause mortality, non-fatal MI, incident heart failure (HF)&#xD;
           hospitalization or emergent/urgent coronary revascularization;&#xD;
&#xD;
        -  Costs of diagnostic testing and treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 8, 2020</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2022</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>Crossover Assignment</intervention_model>
    <intervention_model_description>Stepped-wedge cluster-randomized trial. Unidirectional crossover design where clusters cross over sequentially, in random order, from the control to intervention phase.</intervention_model_description>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients with all-cause mortality, non-fatal myocardial infarction, hospitalization for incident heart failure, or urgent/emergent coronary revascularization (percutaneous coronary intervention or coronary artery bypass surgery)</measure>
    <time_frame>1-year post index emergency department presentation</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with a) Non-fatal myocardial infarction or all-cause mortality; b) Urgent/emergent coronary revascularization or all-cause mortality; c) Hospitalization for heart failure or all-cause mortality.</measure>
    <time_frame>1-year post index emergency department presentation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients who fill at least one prescription for evidence-based cardiac medications</measure>
    <time_frame>Within 90 days of ED visit</time_frame>
    <description>Medications include beta-blockers, Angiotensin Converting Enzyme (ACE)-I/Angiotensin II receptor blockers (ARB), statins, anti-platelets</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients who undergo diagnostic tests</measure>
    <time_frame>Within 90 days of ED visit</time_frame>
    <description>Diagnostic tests include nuclear medicine cardiac scan, exercise stress test, diagnostic cardiac catheterization/CT angiogram or echocardiogram</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">24000</enrollment>
  <condition>Myocardial Infarction</condition>
  <condition>Sex Differences</condition>
  <condition>High Sensitivity Troponin</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The intervention is the introduction of a lower female threshold. In cluster-randomized trials, the cluster (i.e., hospital) is the unit of randomization.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The control phase will be standard of care, with the use of an overall population hs-cTn T and I threshold, for both men and women, to identify those with myocardial injury/infarction.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Introduction of a lower female hs-cTn threshold</intervention_name>
    <description>The new female hs-cTn threshold will be baed on current recommendations for each of the assays used (hs-cTn T and I). The hospitals are the unit of randomization. At 5-month intervals, randomly selected hospitals will be advised that they are to transition to the intervention phase. For all men, the standard of care, overall population threshold will be used throughout the entire study.</description>
    <arm_group_label>Intervention</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  &gt;20 years of age&#xD;
&#xD;
          -  Present to the ED with chest pain or shortness of breath suggestive of ischemia&#xD;
&#xD;
          -  Have a valid personal health identifier&#xD;
&#xD;
          -  Have 1 hs-cTn test result&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have ST elevation myocardial infarction (STEMI)&#xD;
&#xD;
          -  Not residents in the same province as the hospital ED to which they present or move&#xD;
             out of province within a year&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Karin Humphries, DSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medicine, Cardiology, UBC, BC Centre for Improved Cardiovascular Health</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mona Izadnegahdar, PhD</last_name>
    <phone>604-6822344</phone>
    <phone_ext>66794</phone_ext>
    <email>mizadnegahdar@icvhealth.ubc.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Salima Jutha, CCRA</last_name>
    <phone>604-806-9119</phone>
    <email>CodeMI@icvhealth.ubc.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>St. Paul's Hospital</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mona Izadnegahdar, PhD</last_name>
      <email>mizadnegahdar@icvhealth.ubc.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>January 21, 2019</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>August 23, 2021</last_update_submitted>
  <last_update_submitted_qc>August 23, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>myocardial infarction</keyword>
  <keyword>sex differences</keyword>
  <keyword>high-sensitivity cardiac troponin</keyword>
  <keyword>biomarkers</keyword>
  <keyword>heart attack</keyword>
  <keyword>emergency department</keyword>
  <keyword>acute coronary syndrome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myocardial Infarction</mesh_term>
    <mesh_term>Hypersensitivity</mesh_term>
    <mesh_term>Infarction</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/NCT03819894
org study id: H18-02116
nct id: NCT03819894
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The project is focussed on evaluating the impact of using a female-specific threshold in the
      diagnosis of myocardial infarction. This female threshold is lower than the overall hs-cTn
      threshold currently in use. The investigators hypothesize that this change in process,
      applied at the hospital level, will lead to better assessment, treatment and outcomes of
      women presenting to the emergency department with chest pain that is cardiac in nature.
In subjects with suspected acute coronary syndromes (ACS), females are significantly less
      likely to undergo investigations, receive evidence-based treatments, and consistently have
      worse outcomes than males. The gap in outcomes is particularly marked among adults < 55 years
      of age. Sex differences in symptom presentation and in the diagnostic threshold for cardiac
      biomarkers have been suggested as reasons for the under-diagnosis and under-treatment of
      women. Cardiac troponin (cTn) T and I are proteins specific to the myocardium, which with
      elevated and changing concentrations detected in the blood, along with signs or symptoms
      consistent with myocardial ischemia, are indicative of a diagnosis of myocardial infarction
      (MI). With the introduction of high-sensitivity (hs) cTn tests, which allow the detection of
      very low concentrations of troponin, it has become evident that the level of cTn in a healthy
      population is approximately two-fold higher in males than in females.

      Consequently, the 99th percentile threshold for cTn, the reference value used in diagnosis of
      MI, is lower in females compared to males. Despite this evidence and recent guidelines
      recommending the use of sex specific thresholds, a single, overall cTn threshold is still
      being used for diagnosis of MI, in both men and women, in most clinical settings.

      There is mounting evidence from several jurisdictions that the rate of MI is increasing among
      younger females, and that there is a persistent under-diagnosis, under-treatment, and high
      risk of adverse outcomes among females, especially younger females, compared to their male
      counterparts. A better approach to the diagnostic assessment of females presenting to the
      emergency department (ED) with chest pain is therefore urgently needed. Additionally, several
      Canadian hospitals have recently made the transition from sensitive to high sensitivity cTn
      assays, allowing for the examination of subtle but important sex-specific differences in cTn
      concentrations. With this background, the investigators propose a nationwide, randomized
      clinical trial (RCT) to determine whether establishing female thresholds results in improved
      diagnosis and treatment of MI and therefore improved prognosis in women.

      To determine whether the use of female hs-cTn thresholds in the assessment of women
      presenting to the ED with chest pain suggestive of cardiac ischemia, improves diagnostic
      assessment, treatment and 1-year outcomes. Specifically, the investigators will examine the
      impact of using female hs-cTn thresholds on:

        -  Diagnostic and therapeutic strategies;

        -  Prognosis: 1-year all-cause mortality, non-fatal MI, incident heart failure (HF)
           hospitalization or emergent/urgent coronary revascularization;

        -  Costs of diagnostic testing and treatment.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Stepped-wedge cluster-randomized trial. Unidirectional crossover design where clusters cross over sequentially, in random order, from the control to intervention phase.
primary purpose: Health Services Research
masking: Double (Participant, Outcomes Assessor)
measure: Number of patients with all-cause mortality, non-fatal myocardial infarction, hospitalization for incident heart failure, or urgent/emergent coronary revascularization (percutaneous coronary intervention or coronary artery bypass surgery)
time frame: 1-year post index emergency department presentation
measure: Number of patients with a) Non-fatal myocardial infarction or all-cause mortality; b) Urgent/emergent coronary revascularization or all-cause mortality; c) Hospitalization for heart failure or all-cause mortality.
time frame: 1-year post index emergency department presentation
measure: Proportion of patients who fill at least one prescription for evidence-based cardiac medications
time frame: Within 90 days of ED visit
description: Medications include beta-blockers, Angiotensin Converting Enzyme (ACE)-I/Angiotensin II receptor blockers (ARB), statins, anti-platelets
measure: Proportion of patients who undergo diagnostic tests
time frame: Within 90 days of ED visit
description: Diagnostic tests include nuclear medicine cardiac scan, exercise stress test, diagnostic cardiac catheterization/CT angiogram or echocardiogram
arm group label: Intervention
arm group type: Experimental
description: The intervention is the introduction of a lower female threshold. In cluster-randomized trials, the cluster (i.e., hospital) is the unit of randomization.
arm group label: Control
arm group type: No Intervention
description: The control phase will be standard of care, with the use of an overall population hs-cTn T and I threshold, for both men and women, to identify those with myocardial injury/infarction.
intervention type: Diagnostic Test
intervention name: Introduction of a lower female hs-cTn threshold
description: The new female hs-cTn threshold will be baed on current recommendations for each of the assays used (hs-cTn T and I). The hospitals are the unit of randomization. At 5-month intervals, randomly selected hospitals will be advised that they are to transition to the intervention phase. For all men, the standard of care, overall population threshold will be used throughout the entire study.
arm group label: Intervention
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Karin Humphries, DSc
role: Principal Investigator
affiliation: Medicine, Cardiology, UBC, BC Centre for Improved Cardiovascular Health
last name: Mona Izadnegahdar, PhD
phone: 604-6822344
phone ext: 66794
email: mizadnegahdar@icvhealth.ubc.ca
last name: Salima Jutha, CCRA
phone: 604-806-9119
email: CodeMI@icvhealth.ubc.ca
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Sponsor
mesh term: Myocardial Infarction
mesh term: Hypersensitivity
mesh term: Infarction