<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/NCT02261870</url>
  </required_header>
  <id_info>
    <org_study_id>2014-A00848-39</org_study_id>
    <secondary_id>CIC1433</secondary_id>
    <nct_id>NCT02261870</nct_id>
  </id_info>
  <brief_title>Detection of Acute Graft Rejection in Heart Transplant Patients by Estimation of T2</brief_title>
  <acronym>DRAGET</acronym>
  <official_title>&quot;Detection of Acute Rejection in Heart Transplant Patients by Mean of T2 Quantification With MRI&quot; Open Transversal Clinical Trial With Repeated Measures</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Central Hospital, Nancy, France</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Central Hospital, Nancy, France</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators propose a simple and non-invasive method to monitor heart transplant&#xD;
      patients with MRI. Its diagnostic and prognostic values have already been assessed in two&#xD;
      monocentric studies. Other monocentric studies based on related methods have confirmed the&#xD;
      investigators findings. These studies are insufficient to allow a large diffusion of the&#xD;
      technique. Only a large multi-centric study will change medical practices. In addition, this&#xD;
      project will spread the new method at a national level and will allow an assessment of its&#xD;
      practical usefulness in centres not familiar with MRI T2 quantification.&#xD;
&#xD;
      Furthermore, MRI seems to detect rejections at earlier stage than biopsy. A confirmation of&#xD;
      this observation could lead to a modification of diagnostic criteria of cardiac graft&#xD;
      rejection. The ultimate aim of the DRAGET project is to replace a strategy based solely on&#xD;
      biopsy with one based on a first-line MRI (with biopsy only when needed) for a more efficient&#xD;
      and earlier detection of rejection. This would constitute a major advance in patients&#xD;
      security and comfort as well as an economic improvement.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 18, 2015</start_date>
  <completion_date type="Actual">February 27, 2020</completion_date>
  <primary_completion_date type="Actual">February 27, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Sensitivity and specificity of myocardial T2 assessed with MRI for the diagnosis of histological heart graft rejection (with 95% confidence interval).</measure>
    <time_frame>3 years after first inclusion</time_frame>
    <description>endpoint = sensitivity and specificity acute rejection means presence of damaged myocytes in endomyocardial biopsy (former grade 2, grade 2R and grade 3R)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of histological or clinical rejection within months of a couple MRI/biopsy with normal biopsy (grade&lt;2R).</measure>
    <time_frame>3 years after first inclusion</time_frame>
    <description>endpoint = number of rejections For this purpose, rejection will be defined as: a) acute rejection documented by presence of damaged myocytes in endomyocardial biopsy (former grade 2, grade 2R and grade 3R), or b) marked decrease in left ventricle ejection fraction (&gt;10%), reversible after subsequent increase in immunosuppressive treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complications with MRI and with biopsies.</measure>
    <time_frame>3 years after first inclusion</time_frame>
    <description>endpoint = Number of adverse events due to both exams</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Magnitude of better tolerability of MRI over biopsies for the patient.</measure>
    <time_frame>3 years after first inclusion</time_frame>
    <description>endpoint = Physical and psychological distress assessed by questionnaire using Likert scales. This questionnaire will be completed by the patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inter-observer reproducibility of T2 quantification with MRI and of pathological grading of the biopsies.</measure>
    <time_frame>3 years after first inclusion</time_frame>
    <description>endpoint = 95% interobserver limit of agreement for T2 quantification and Cohen's Kappa coefficient for histological grading.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Level of confidence, at the end of the study, of the expert-physicians of each centre concerning the use of T2 quantification as an alternative to routine biopsies.</measure>
    <time_frame>3 years after first inclusion</time_frame>
    <description>endpoint = Confidence assessed by questionnaire using Likert scales. This questionnaire will be completed by study investigators at the end of the study.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">116</enrollment>
  <condition>Acute Graft Rejection</condition>
  <condition>Heart Transplantation</condition>
  <arm_group>
    <arm_group_label>ALL_patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MRI T2 quantification : heart transplant patients will have 4-6 MRI exams for T2 quantification during their first year after transplantation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MRI T2 quantification</intervention_name>
    <description>MRI acquisitions will be performed according to the already described method based on conventional Fast Spin Echo sequences and with an additional calibration pad positioned on the patient thorax (dedicated pad made by the Nancy CIC-IT with stable and adapted T2). MRI will be performed if possible before the biopsy and otherwise the radiologist will be kept blinded of the biopsy results.</description>
    <arm_group_label>ALL_patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Heart transplant patient&#xD;
&#xD;
          -  Able to realize 4 couples Biopsy/MRI within 12 months after the transplant&#xD;
&#xD;
          -  Mandatory enrolment in a social security plan&#xD;
&#xD;
          -  Patient having signed an informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Contraindication to MRI: pacemaker, ferromagnetic foreign body, etc&#xD;
&#xD;
          -  Impossibility to undergo MRI: claustrophobia, morbid obesity, hospitalisation in&#xD;
             intensive care unit, arrhythmia&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Patients under a measure of legal protection&#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>Laurent Bonnemains, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>INSERM, IADI U47, Nancy, France</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospices Civils de Lyon</name>
      <address>
        <city>Bron</city>
        <zip>69677</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Grenoble</name>
      <address>
        <city>La Tronche</city>
        <zip>38700</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHRU Nancy Brabois</name>
      <address>
        <city>Nancy</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Nantes</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Européen Georges Pompidou</name>
      <address>
        <city>Paris</city>
        <zip>75015</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Groupe Hospitalier Pitié-Salpêtrière</name>
      <address>
        <city>Paris</city>
        <zip>75651</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Bordeaux</name>
      <address>
        <city>Pessac</city>
        <zip>33604</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Rennes</name>
      <address>
        <city>Rennes</city>
        <zip>35033</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopitaux Universitaires de Strasbourg</name>
      <address>
        <city>Strasbourg</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Tours</name>
      <address>
        <city>Tours</city>
        <zip>37044</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>September 25, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 10, 2014</study_first_posted>
  <last_update_submitted>May 11, 2020</last_update_submitted>
  <last_update_submitted_qc>May 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MRI, T2 quantification</keyword>
  <!-- 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/NCT02261870
org study id: 2014-A00848-39
secondary id: CIC1433
nct id: NCT02261870
lead sponsor: 
has dmc: No
The investigators propose a simple and non-invasive method to monitor heart transplant
      patients with MRI. Its diagnostic and prognostic values have already been assessed in two
      monocentric studies. Other monocentric studies based on related methods have confirmed the
      investigators findings. These studies are insufficient to allow a large diffusion of the
      technique. Only a large multi-centric study will change medical practices. In addition, this
      project will spread the new method at a national level and will allow an assessment of its
      practical usefulness in centres not familiar with MRI T2 quantification.

      Furthermore, MRI seems to detect rejections at earlier stage than biopsy. A confirmation of
      this observation could lead to a modification of diagnostic criteria of cardiac graft
      rejection. The ultimate aim of the DRAGET project is to replace a strategy based solely on
      biopsy with one based on a first-line MRI (with biopsy only when needed) for a more efficient
      and earlier detection of rejection. This would constitute a major advance in patients
      security and comfort as well as an economic improvement.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Sensitivity and specificity of myocardial T2 assessed with MRI for the diagnosis of histological heart graft rejection (with 95% confidence interval).
time frame: 3 years after first inclusion
description: endpoint = sensitivity and specificity acute rejection means presence of damaged myocytes in endomyocardial biopsy (former grade 2, grade 2R and grade 3R)
measure: Incidence of histological or clinical rejection within months of a couple MRI/biopsy with normal biopsy (grade<2R).
time frame: 3 years after first inclusion
description: endpoint = number of rejections For this purpose, rejection will be defined as: a) acute rejection documented by presence of damaged myocytes in endomyocardial biopsy (former grade 2, grade 2R and grade 3R), or b) marked decrease in left ventricle ejection fraction (>10%), reversible after subsequent increase in immunosuppressive treatment.
measure: Complications with MRI and with biopsies.
time frame: 3 years after first inclusion
description: endpoint = Number of adverse events due to both exams
measure: Magnitude of better tolerability of MRI over biopsies for the patient.
time frame: 3 years after first inclusion
description: endpoint = Physical and psychological distress assessed by questionnaire using Likert scales. This questionnaire will be completed by the patients.
measure: Inter-observer reproducibility of T2 quantification with MRI and of pathological grading of the biopsies.
time frame: 3 years after first inclusion
description: endpoint = 95% interobserver limit of agreement for T2 quantification and Cohen's Kappa coefficient for histological grading.
measure: Level of confidence, at the end of the study, of the expert-physicians of each centre concerning the use of T2 quantification as an alternative to routine biopsies.
time frame: 3 years after first inclusion
description: endpoint = Confidence assessed by questionnaire using Likert scales. This questionnaire will be completed by study investigators at the end of the study.
arm group label: ALL_patients
arm group type: Experimental
description: MRI T2 quantification : heart transplant patients will have 4-6 MRI exams for T2 quantification during their first year after transplantation.
intervention type: Device
intervention name: MRI T2 quantification
description: MRI acquisitions will be performed according to the already described method based on conventional Fast Spin Echo sequences and with an additional calibration pad positioned on the patient thorax (dedicated pad made by the Nancy CIC-IT with stable and adapted T2). MRI will be performed if possible before the biopsy and otherwise the radiologist will be kept blinded of the biopsy results.
arm group label: ALL_patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Laurent Bonnemains, MD, PhD
role: Principal Investigator
affiliation: INSERM, IADI U47, Nancy, France
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor