<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/NCT03005158</url>
  </required_header>
  <id_info>
    <org_study_id>PG/15/51/31596</org_study_id>
    <nct_id>NCT03005158</nct_id>
  </id_info>
  <brief_title>High-Sensitivity Cardiac Troponin On Presentation to Rule Out Myocardial Infarction</brief_title>
  <acronym>HiSTORIC</acronym>
  <official_title>High-Sensitivity Cardiac Troponin On Presentation to Rule Out Myocardial Infarction (HiSTORIC): A Stepped Wedge Cluster Randomized Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Edinburgh</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>NHS Lothian</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>NHS Greater Glasgow and Clyde</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Edinburgh</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with suspected acute coronary syndrome account for a tenth of all presentations to&#xD;
      the Emergency Department and up to 40 per cent of unplanned hospital admissions. The majority&#xD;
      of patients do not have a heart attack (myocardial infarction), and may be safely discharged&#xD;
      from the Emergency Department.&#xD;
&#xD;
      The investigators propose to evaluate whether the use of the HighSTEACS pathway in patients&#xD;
      with suspected acute coronary syndrome reduces length of stay and allows more patients to be&#xD;
      safely discharged from the Emergency Department. This pathways utilizes high-sensitivity&#xD;
      cardiac troponin I testing and will rule out myocardial infarction if troponin concentrations&#xD;
      are &lt;5 ng/L on presentation, with further testing indicated at 3 hours only in those&#xD;
      presenting early or with troponin concentrations between 5 ng/L and the 99th centile.&#xD;
&#xD;
      In six secondary and tertiary centres across Scotland, the investigators will introduce the&#xD;
      pathway as part of a stepped wedge cluster randomized controlled trial. Sequential hypothesis&#xD;
      testing will evaluate the efficacy and safety of the pathway. The primary efficacy end-point&#xD;
      will be length of stay from time of presentation until final hospital discharge and the&#xD;
      primary safety end-point will be survival free from type 1 or 4b myocardial infarction or&#xD;
      cardiac death from discharge to 30 days. The study population will consist of those patients&#xD;
      with cardiac troponin concentrations within the normal reference range (&lt;99th centile) at&#xD;
      presentation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">November 2014</start_date>
  <completion_date type="Anticipated">December 2, 2021</completion_date>
  <primary_completion_date type="Actual">January 2, 2017</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>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Length of hospital stay (minutes)</measure>
    <time_frame>Length of time from initial presentation to the Emergency Department until final discharge from hospital, an average of 24 hours.</time_frame>
    <description>This time frame is unique to each patient</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Type 1 or type 4b myocardial infarction or cardiac death after discharge and within 30 days of index admission</measure>
    <time_frame>Hospital discharge to 30 days after initial presentation</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients discharged directly home from the Emergency Department</measure>
    <time_frame>Presentation to discharge from hospital, an average of 24 hours.</time_frame>
    <description>Time frame of initial hospital episode is unique to each patient</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Type 1 or 4b Myocardial Infarction after hospital discharge (independently double adjudicated using all available clinical information)</measure>
    <time_frame>Hospital discharge to 30 days and 1 year after initial presentation</time_frame>
    <description>An adjudicated diagnosis of type 1 and type 4b myocardial infarction will be made in line with the universal definition of myocardial infarction, using all available clinical information.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac death after hospital discharge (independently double adjudicated using all available clinical information)</measure>
    <time_frame>Hospital discharge to 30 days and 1 year after initial presentation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiovascular death after hospital discharge (independently double adjudicated using all available clinical information)</measure>
    <time_frame>Hospital discharge to 30 days and 1 year after initial presentation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause death after hospital discharge</measure>
    <time_frame>Hospital discharge to 30 days and 1 year after initial presentation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unplanned coronary revascularisation after hospital discharge (from cardiac intervention databases and case note review)</measure>
    <time_frame>Hospital discharge to 30 days and 1 year after initial presentation</time_frame>
    <description>We will identify any patients who require unplanned percutaneous coronary intervention or coronary artery bypass grafting.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients re-attending the Emergency Department</measure>
    <time_frame>Hospital discharge to 30 days and 1 year after initial presentation</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Pre-specified sub-group analyses of the primary outcome</measure>
    <time_frame>length of hospital stay defined as the length of time from initial presentation to the Emergency Department until final discharge from hospital; safety follow-up time frame of 30 days and 1 year after hospital discharge</time_frame>
    <description>We will evaluate if the effect of intervention is significantly stronger or weaker in pre-specified sub-groups by assessing the co-primary endpoints in those who present with cardiac troponin &lt;5 ng/L (low risk group), and in the whole population across different ages (considering age as a continuous variable), by duration of symptoms (considered as a continuous variable), by gender, by those who have or do not have a pre-existing history of ischaemic heart disease, by those with a presentation electrocardiogram suggesting ischaemia, by the GRACE risk score (considered as a continuous variable), and by day of patient presentation (assessing differences in weekday/weekend or routine/out-of-hours presentation).</description>
  </other_outcome>
  <other_outcome>
    <measure>Cost-effectiveness analysis</measure>
    <time_frame>1 year</time_frame>
    <description>Based on costs of investigation and management in the year after initial hospital presentation</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">39000</enrollment>
  <condition>Acute Coronary Syndrome</condition>
  <condition>Myocardial Infarction</condition>
  <arm_group>
    <arm_group_label>Validation Phase</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All six hospital sites currently use the ARCHITECT STAT high- sensitive troponin I assay in the assessment of patients with suspected acute coronary syndrome and use sex-specific thresholds upper reference limits (99th centile) to rule out myocardial infarction. This validation phase of up to 10 months will provide baseline information for each site on patients with suspected acute coronary syndrome in whom myocardial infarction is ruled out.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Randomization Phase</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participating centres will be randomized to implement the HighSTEACS pathway (intervention). The order of implementation will be randomized, with paired participating centres implementing in steps over a 6 month period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Implementation Phase</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A final phase of up to 10 months after implementation of the HighSTEACS pathway will be matched by calendar month in each site to that of the validation phase, allowing each participating centre to act as its own control and to adjust for seasonal differences in the incidence of myocardial infarction and mortality.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Validation Phase</intervention_name>
    <description>Standard care across all sites during the validation phase will rule out myocardial infarction in those with presentation troponin below the 99th centile with greater than 6 hours of symptoms at the time of blood sampling. In those with less than 6 hours of symptoms, a second test will be measured 6- 12 hours after presentation.</description>
    <arm_group_label>Validation Phase</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Randomization Phase</intervention_name>
    <description>Standard care or HighSTEACS pathway.</description>
    <arm_group_label>Randomization Phase</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Implementation Phase</intervention_name>
    <description>Implementation of the HighSTEACS pathway to rule out myocardial infarction in patients with suspected acute coronary syndrome. Myocardial infarction will be ruled out if presentation cardiac troponin concentrations are &lt;5 ng/L in those with at least 2 hours of symptoms at the time of blood sampling. In patients with less than two hours of symptoms, or where cardiac troponin concentrations are between 5ng/L and the 99th centile, repeat testing will be recommended at 3 hours. Myocardial infarction will be ruled out at 3 hours if cardiac troponin concentrations are unchanged (&lt;3 ng/L change) and remain ≤99th centile on retesting. Those remaining ≤99th centile on retesting but demonstrating a significant change will require admission for further testing at 6-12 hours.</description>
    <arm_group_label>Implementation Phase</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All consecutive patients with suspected acute coronary syndrome&#xD;
&#xD;
          -  High-sensitivity cardiac troponin I measured as part of routine clinical care&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who are not resident in Scotland&#xD;
&#xD;
          -  Patients with ST-segment elevation myocardial infarction&#xD;
&#xD;
          -  Patients presenting to hospital in cardiac arrest&#xD;
&#xD;
          -  Patients with presentation high-sensitivity cardiac troponin I concentrations greater&#xD;
             than sex-specific 99th centile thresholds&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nicholas L Mills, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Edinburgh</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ian Ford, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Glasgow</affiliation>
  </overall_official>
  <reference>
    <citation>Shah AS, Anand A, Sandoval Y, Lee KK, Smith SW, Adamson PD, Chapman AR, Langdon T, Sandeman D, Vaswani A, Strachan FE, Ferry A, Stirzaker AG, Reid A, Gray AJ, Collinson PO, McAllister DA, Apple FS, Newby DE, Mills NL; High-STEACS investigators. High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort study. Lancet. 2015 Dec 19;386(10012):2481-8. doi: 10.1016/S0140-6736(15)00391-8. Epub 2015 Oct 8.</citation>
    <PMID>26454362</PMID>
  </reference>
  <reference>
    <citation>Shah ASV, Anand A, Chapman AR, Newby DE, Mills NL; High-STEACS Investigators. Measurement of cardiac troponin for exclusion of myocardial infarction - Authors' reply. Lancet. 2016 Jun 4;387(10035):2289-2291. doi: 10.1016/S0140-6736(16)30517-7. No abstract available.</citation>
    <PMID>27302263</PMID>
  </reference>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>August 15, 2016</study_first_submitted>
  <study_first_submitted_qc>December 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 29, 2016</study_first_posted>
  <last_update_submitted>May 28, 2019</last_update_submitted>
  <last_update_submitted_qc>May 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 29, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>High-sensitivity cardiac troponin I</keyword>
  <keyword>Myocardial infarction</keyword>
  <keyword>Acute coronary syndrome</keyword>
  <keyword>Cluster-randomized trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myocardial Infarction</mesh_term>
    <mesh_term>Acute Coronary Syndrome</mesh_term>
    <mesh_term>Hypersensitivity</mesh_term>
    <mesh_term>Infarction</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03005158
org study id: PG/15/51/31596
nct id: NCT03005158
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Patients with suspected acute coronary syndrome account for a tenth of all presentations to
      the Emergency Department and up to 40 per cent of unplanned hospital admissions. The majority
      of patients do not have a heart attack (myocardial infarction), and may be safely discharged
      from the Emergency Department.

      The investigators propose to evaluate whether the use of the HighSTEACS pathway in patients
      with suspected acute coronary syndrome reduces length of stay and allows more patients to be
      safely discharged from the Emergency Department. This pathways utilizes high-sensitivity
      cardiac troponin I testing and will rule out myocardial infarction if troponin concentrations
      are <5 ng/L on presentation, with further testing indicated at 3 hours only in those
      presenting early or with troponin concentrations between 5 ng/L and the 99th centile.

      In six secondary and tertiary centres across Scotland, the investigators will introduce the
      pathway as part of a stepped wedge cluster randomized controlled trial. Sequential hypothesis
      testing will evaluate the efficacy and safety of the pathway. The primary efficacy end-point
      will be length of stay from time of presentation until final hospital discharge and the
      primary safety end-point will be survival free from type 1 or 4b myocardial infarction or
      cardiac death from discharge to 30 days. The study population will consist of those patients
      with cardiac troponin concentrations within the normal reference range (<99th centile) at
      presentation.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Diagnostic
masking: Single (Outcomes Assessor)
measure: Length of hospital stay (minutes)
time frame: Length of time from initial presentation to the Emergency Department until final discharge from hospital, an average of 24 hours.
description: This time frame is unique to each patient
measure: Type 1 or type 4b myocardial infarction or cardiac death after discharge and within 30 days of index admission
time frame: Hospital discharge to 30 days after initial presentation
measure: Proportion of patients discharged directly home from the Emergency Department
time frame: Presentation to discharge from hospital, an average of 24 hours.
description: Time frame of initial hospital episode is unique to each patient
measure: Type 1 or 4b Myocardial Infarction after hospital discharge (independently double adjudicated using all available clinical information)
time frame: Hospital discharge to 30 days and 1 year after initial presentation
description: An adjudicated diagnosis of type 1 and type 4b myocardial infarction will be made in line with the universal definition of myocardial infarction, using all available clinical information.
measure: Cardiac death after hospital discharge (independently double adjudicated using all available clinical information)
time frame: Hospital discharge to 30 days and 1 year after initial presentation
measure: Cardiovascular death after hospital discharge (independently double adjudicated using all available clinical information)
time frame: Hospital discharge to 30 days and 1 year after initial presentation
measure: All-cause death after hospital discharge
time frame: Hospital discharge to 30 days and 1 year after initial presentation
measure: Unplanned coronary revascularisation after hospital discharge (from cardiac intervention databases and case note review)
time frame: Hospital discharge to 30 days and 1 year after initial presentation
description: We will identify any patients who require unplanned percutaneous coronary intervention or coronary artery bypass grafting.
measure: Proportion of patients re-attending the Emergency Department
time frame: Hospital discharge to 30 days and 1 year after initial presentation
measure: Pre-specified sub-group analyses of the primary outcome
time frame: length of hospital stay defined as the length of time from initial presentation to the Emergency Department until final discharge from hospital; safety follow-up time frame of 30 days and 1 year after hospital discharge
description: We will evaluate if the effect of intervention is significantly stronger or weaker in pre-specified sub-groups by assessing the co-primary endpoints in those who present with cardiac troponin <5 ng/L (low risk group), and in the whole population across different ages (considering age as a continuous variable), by duration of symptoms (considered as a continuous variable), by gender, by those who have or do not have a pre-existing history of ischaemic heart disease, by those with a presentation electrocardiogram suggesting ischaemia, by the GRACE risk score (considered as a continuous variable), and by day of patient presentation (assessing differences in weekday/weekend or routine/out-of-hours presentation).
measure: Cost-effectiveness analysis
time frame: 1 year
description: Based on costs of investigation and management in the year after initial hospital presentation
arm group label: Validation Phase
arm group type: Other
description: All six hospital sites currently use the ARCHITECT STAT high- sensitive troponin I assay in the assessment of patients with suspected acute coronary syndrome and use sex-specific thresholds upper reference limits (99th centile) to rule out myocardial infarction. This validation phase of up to 10 months will provide baseline information for each site on patients with suspected acute coronary syndrome in whom myocardial infarction is ruled out.
arm group label: Randomization Phase
arm group type: Other
description: Participating centres will be randomized to implement the HighSTEACS pathway (intervention). The order of implementation will be randomized, with paired participating centres implementing in steps over a 6 month period.
arm group label: Implementation Phase
arm group type: Active Comparator
description: A final phase of up to 10 months after implementation of the HighSTEACS pathway will be matched by calendar month in each site to that of the validation phase, allowing each participating centre to act as its own control and to adjust for seasonal differences in the incidence of myocardial infarction and mortality.
intervention type: Other
intervention name: Validation Phase
description: Standard care across all sites during the validation phase will rule out myocardial infarction in those with presentation troponin below the 99th centile with greater than 6 hours of symptoms at the time of blood sampling. In those with less than 6 hours of symptoms, a second test will be measured 6- 12 hours after presentation.
arm group label: Validation Phase
intervention type: Other
intervention name: Randomization Phase
description: Standard care or HighSTEACS pathway.
arm group label: Randomization Phase
intervention type: Other
intervention name: Implementation Phase
description: Implementation of the HighSTEACS pathway to rule out myocardial infarction in patients with suspected acute coronary syndrome. Myocardial infarction will be ruled out if presentation cardiac troponin concentrations are <5 ng/L in those with at least 2 hours of symptoms at the time of blood sampling. In patients with less than two hours of symptoms, or where cardiac troponin concentrations are between 5ng/L and the 99th centile, repeat testing will be recommended at 3 hours. Myocardial infarction will be ruled out at 3 hours if cardiac troponin concentrations are unchanged (<3 ng/L change) and remain ≤99th centile on retesting. Those remaining ≤99th centile on retesting but demonstrating a significant change will require admission for further testing at 6-12 hours.
arm group label: Implementation Phase
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Nicholas L Mills, MD, PhD
role: Principal Investigator
affiliation: University of Edinburgh
last name: Ian Ford, PhD
role: Study Chair
affiliation: University of Glasgow
citation: Shah AS, Anand A, Sandoval Y, Lee KK, Smith SW, Adamson PD, Chapman AR, Langdon T, Sandeman D, Vaswani A, Strachan FE, Ferry A, Stirzaker AG, Reid A, Gray AJ, Collinson PO, McAllister DA, Apple FS, Newby DE, Mills NL; High-STEACS investigators. High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort study. Lancet. 2015 Dec 19;386(10012):2481-8. doi: 10.1016/S0140-6736(15)00391-8. Epub 2015 Oct 8.
PMID: 26454362
citation: Shah ASV, Anand A, Chapman AR, Newby DE, Mills NL; High-STEACS Investigators. Measurement of cardiac troponin for exclusion of myocardial infarction - Authors' reply. Lancet. 2016 Jun 4;387(10035):2289-2291. doi: 10.1016/S0140-6736(16)30517-7. No abstract available.
PMID: 27302263
responsible party type: Sponsor
mesh term: Myocardial Infarction
mesh term: Acute Coronary Syndrome
mesh term: Hypersensitivity
mesh term: Infarction
sharing ipd: Undecided