<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/NCT03022487</url>
  </required_header>
  <id_info>
    <org_study_id>0556</org_study_id>
    <secondary_id>186618</secondary_id>
    <secondary_id>16/NI/0069</secondary_id>
    <nct_id>NCT03022487</nct_id>
  </id_info>
  <brief_title>Multicentre Investigation of Novel Electrocardiogram Risk Markers in Ventricular Arrhythmia Prediction</brief_title>
  <acronym>MINERVA</acronym>
  <official_title>Multicentre Investigation of Novel Electrocardiogram Risk Markers in Ventricular Arrhythmia Prediction (MINERVA)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Leicester</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Leicester</source>
  <brief_summary>
    <textblock>
      This is a prospective open label single blinded multi-centre observational study involving a&#xD;
      study group of patients already undergoing implantable cardioverter-defibrillator&#xD;
      (ICD)(including Cardiac resynchronisation therapy device (CRT-D)) implant. A standard&#xD;
      30-minute electrophysiological (EP) cardiac stimulation protocol will be performed at the end&#xD;
      of the ICD implant at baseline. This EP test will be performed whilst measuring a 12-lead ECG&#xD;
      and will be correlated with event rates to establish their effectiveness in predicting&#xD;
      arrhythmia risk. The minimum follow up period should be 18 months and maximum of 3 years,&#xD;
      which is how long the study is funded for. This study is not randomised as all study patients&#xD;
      will be receiving the EP study performed at baseline. A minimum of 440 patients will be&#xD;
      recruited to document event data at standard clinical ICD follow up intervals - equating to a&#xD;
      maximum of 6 visits. Blinding will be maintained at the core lab were the ECG analysis will&#xD;
      be performed by a nominated researcher who will not have details of patient health status.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>July 8, 2016</start_date>
  <completion_date type="Anticipated">September 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Regional Restitution Instability Index (R2I2), the mean of the standard deviation of the residuals from the mean gradients for each ECG lead across a range of diastolic intervals, will be determined from an EP study carried out at ICD implant.</measure>
    <time_frame>12 - 36 months</time_frame>
    <description>For each lead of the surface ECG, the QTpeak will be plotted as a function of TpeakQ, and gradients were fitted by using 40ms overlapping least squares linear segments as described previously by Taggart et al. [9]. For each lead, in each 40 ms segment, the difference of the gradient from the mean gradient in that 40 ms segment will be calculated. The mean of the standard deviation of these values will be taken as the R2I2.&#xD;
An R2I2 cut-off of 1.03 (no units) will partition the study population into high and low risk groups.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Peak ECG Restitution Slope (PERS), calculated as the peak restitution curve slope taken as a mean across the 12 ECG leads .</measure>
    <time_frame>12 - 36 months</time_frame>
    <description>A PERS cut-off of 1.21 (no units) will partition the study population into high and low risk groups.</description>
  </primary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Anticipated">440</enrollment>
  <condition>Ventricular Arrythmia</condition>
  <condition>Ischemic Cardiomyopathy</condition>
  <arm_group>
    <arm_group_label>ICD Patients with Ischaemic cardiomyopathy</arm_group_label>
    <description>A standard 30-minute electrophysiological (EP) cardiac stimulation protocol will be performed at the end of the ICD implant at baseline. Participants will be followed up for at least 12 months for endpoints.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        440 patients with Ischaemic cardiomyopathy being fitted with an implantable&#xD;
        cardioverter-defibrillator (ICDs)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant is willing and able to give informed consent for participation in the&#xD;
             study&#xD;
&#xD;
          -  Male or Female, aged 18 years or above&#xD;
&#xD;
          -  Female participants of child bearing potential must be willing to ensure that they or&#xD;
             their partner use effective contraception during the study&#xD;
&#xD;
          -  Diagnosed with a history of ischaemic cardiomyopathy&#xD;
&#xD;
          -  Stable, as define as no more than a 100% increase or a 50% decrease, dose of current&#xD;
             regular medication as standard for patients at risk of ventricular arrhythmia for at&#xD;
             least 4 weeks prior to study entry&#xD;
&#xD;
          -  Able (in the Investigators opinion) and willing to comply with all study requirements&#xD;
&#xD;
          -  Willing to allow his or her General Practitioner and consultant, if appropriate, to be&#xD;
             notified of participation in the study&#xD;
&#xD;
          -  Patients must be able to attend follow up at the study site until the study closure&#xD;
&#xD;
          -  Attending for first time primary prevention ICD (including CRT-D) implantation under&#xD;
             THE National Institute for Health and Care Excellence (NICE) criteria&#xD;
&#xD;
          -  Patients must be able to read and understand English&#xD;
&#xD;
          -  Stable dose of current regular medication for at least 4 weeks prior to study entry&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Within 28 days since acute coronary syndrome/cardiac surgery&#xD;
&#xD;
          -  Scheduled elective surgery or other procedures requiring general anaesthesia during&#xD;
             the study: for example - awaiting coronary revascularisation&#xD;
&#xD;
          -  Female participants who are pregnant, lactating or planning pregnancy during the&#xD;
             course of the study&#xD;
&#xD;
          -  Contraindications for electrophysiological study&#xD;
&#xD;
               -  Haemodynamic instability&#xD;
&#xD;
               -  Severe valvular heart disease as define by British Society of Echocardiography&#xD;
                  (BSE) guidelines&#xD;
&#xD;
               -  Symptomatic coronary artery disease (unstable or refractory angina)&#xD;
&#xD;
               -  Stroke within the last 12 months&#xD;
&#xD;
          -  Significant renal disease stage i.e. Chronic Kidney Disease stage 5 (requiring renal&#xD;
             replacement therapy and / or Estimated glomerular filtration rate (eGFR) &lt;15), or&#xD;
             severe liver disease (end stage or presence of cirrhosis)&#xD;
&#xD;
          -  Participants who have participated in another research study involving an&#xD;
             investigational product in the past 12 weeks&#xD;
&#xD;
          -  Undergone ICD implantation where the right ventricular lead is non-apically positioned&#xD;
             e.g. positioned septally&#xD;
&#xD;
          -  Clinically judged by a cardiologist to require a ventricular tachycardia (VT) therapy&#xD;
             zone less than or equal to 200 bpm&#xD;
&#xD;
          -  Any other significant disease or disorders which, in the opinion of the Investigator,&#xD;
             may either put the participants at risk because of participation in the study, or may&#xD;
             influence the result of the study, or the participant's ability to participate in the&#xD;
             study. Specific concerns should be discussed with the Chief / Co - Investigators&#xD;
&#xD;
          -  Any other interventional research&#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_official>
    <last_name>G. André Ng</last_name>
    <role>Study Chair</role>
    <affiliation>University of Leicester</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Michelle Newton</last_name>
    <phone>0116 250 2322</phone>
    <email>mcs33@leicester.ac.uk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hull and East Yorkshire Hospitals NHS Trust</name>
      <address>
        <city>Cottingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location>
    <facility>
      <name>The Dudley Group NHS Foundation Trust</name>
      <address>
        <city>Dudley</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location>
    <facility>
      <name>Leeds Teaching Hospitals NHS Trust</name>
      <address>
        <city>Leeds</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location>
    <facility>
      <name>University Hospitals of Leicester NHS Trust</name>
      <address>
        <city>Leicester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Barts Health NHS Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Imperial college Healthcare NHS Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Nottingham University Hospitals NHS Trust</name>
      <address>
        <city>Nottingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Oxford University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Oxford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>January 9, 2017</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 16, 2017</study_first_posted>
  <last_update_submitted>April 29, 2021</last_update_submitted>
  <last_update_submitted_qc>April 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sudden Cardiac Death (SCD)</keyword>
  <keyword>implantable cardioverter defibrillator</keyword>
  <keyword>electrophysiological</keyword>
  <keyword>EP</keyword>
  <keyword>Ischaemic cardiomyopathy</keyword>
  <keyword>Ventricular Arrhythmia</keyword>
  <keyword>ICD</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiomyopathies</mesh_term>
    <mesh_term>Arrhythmias, Cardiac</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/NCT03022487
org study id: 0556
secondary id: 186618
secondary id: 16/NI/0069
nct id: NCT03022487
lead sponsor: 
This is a prospective open label single blinded multi-centre observational study involving a
      study group of patients already undergoing implantable cardioverter-defibrillator
      (ICD)(including Cardiac resynchronisation therapy device (CRT-D)) implant. A standard
      30-minute electrophysiological (EP) cardiac stimulation protocol will be performed at the end
      of the ICD implant at baseline. This EP test will be performed whilst measuring a 12-lead ECG
      and will be correlated with event rates to establish their effectiveness in predicting
      arrhythmia risk. The minimum follow up period should be 18 months and maximum of 3 years,
      which is how long the study is funded for. This study is not randomised as all study patients
      will be receiving the EP study performed at baseline. A minimum of 440 patients will be
      recruited to document event data at standard clinical ICD follow up intervals - equating to a
      maximum of 6 visits. Blinding will be maintained at the core lab were the ECG analysis will
      be performed by a nominated researcher who will not have details of patient health status.
observational model: Cohort
time perspective: Prospective
measure: Regional Restitution Instability Index (R2I2), the mean of the standard deviation of the residuals from the mean gradients for each ECG lead across a range of diastolic intervals, will be determined from an EP study carried out at ICD implant.
time frame: 12 - 36 months
description: For each lead of the surface ECG, the QTpeak will be plotted as a function of TpeakQ, and gradients were fitted by using 40ms overlapping least squares linear segments as described previously by Taggart et al. [9]. For each lead, in each 40 ms segment, the difference of the gradient from the mean gradient in that 40 ms segment will be calculated. The mean of the standard deviation of these values will be taken as the R2I2.
An R2I2 cut-off of 1.03 (no units) will partition the study population into high and low risk groups.
measure: Peak ECG Restitution Slope (PERS), calculated as the peak restitution curve slope taken as a mean across the 12 ECG leads .
time frame: 12 - 36 months
description: A PERS cut-off of 1.21 (no units) will partition the study population into high and low risk groups.
arm group label: ICD Patients with Ischaemic cardiomyopathy
description: A standard 30-minute electrophysiological (EP) cardiac stimulation protocol will be performed at the end of the ICD implant at baseline. Participants will be followed up for at least 12 months for endpoints.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: G. André Ng
role: Study Chair
affiliation: University of Leicester
last name: Michelle Newton
phone: 0116 250 2322
email: mcs33@leicester.ac.uk
facility: 
status: Not yet recruiting
facility: 
status: Not yet recruiting
facility: 
status: Not yet recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
country: United Kingdom
responsible party type: Sponsor
mesh term: Cardiomyopathies
mesh term: Arrhythmias, Cardiac