<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/NCT03023566</url>
  </required_header>
  <id_info>
    <org_study_id>PCH IRB#16-102</org_study_id>
    <nct_id>NCT03023566</nct_id>
  </id_info>
  <brief_title>Intra-individual Open-label, Single Center Study to Compare Unenhanced MRI With Dotarem Enhanced MRI</brief_title>
  <official_title>Intra-individual Open-label, Single Center Study to Compare Unenhanced MRI With Dotarem Enhanced MRI in Pediatric and Neonatal Patient Population (&lt;18years)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Phoenix Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Guerbet</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Phoenix Children's Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this study is to evaluate safety and efficacy of Dotarem enhanced MRI in&#xD;
      pediatric and neonatal population who are referred for contrast enhanced MRI at Phoenix&#xD;
      Children's Hospital.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Phoenix Children's Hospital (PCH) performs approximately 200 contrast enhanced MRI procedures&#xD;
      per month. Recently PCH changed its MRI contrast agent from the linear contrast agent&#xD;
      Magnevist to the macrocyclic contrast agent Dotarem. The goal of this study is to evaluate&#xD;
      safety and efficacy of Dotarem enhanced MRI in pediatric and neonatal population who are&#xD;
      referred for contrast enhanced MRI at PCH.&#xD;
&#xD;
      The study is designed as a single center, open label comparison of unenhanced MRI with&#xD;
      Dotarem enhanced MRI in pediatric patient population (&lt;18years). The comparison will be&#xD;
      performed intra-individually by 3 independent blinded radiologists. Overall, the study&#xD;
      population will consist of 250 pediatric patients who are indicated for contrast enhanced&#xD;
      MRI. The safety follow-up period will be 24 (+/- 4) hours post injection of Dotarem and&#xD;
      includes the assessment of physical examinations and vital signs as well as the assessment of&#xD;
      AEs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 9, 2017</start_date>
  <completion_date type="Actual">November 12, 2017</completion_date>
  <primary_completion_date type="Actual">November 12, 2017</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>Overall lesion visualization and characterization</measure>
    <time_frame>24 - 48 hours</time_frame>
    <description>Overall lesion visualization and characterization, based on assessment of (1) lesion border delineation, (2) internal morphology and (3) degree of contrast enhancement. All images from &quot;Pre&quot; (unenhanced MRI) and &quot;Paired&quot; (unenhanced + enhanced) MRI will be evaluated independently by the 3 independent readers and are rated on a 3-point scale as unevaluable (0), seen but imperfectly (1) or seen completely/perfectly (2). The primary statistical analysis compared unenhanced MRI to combined MRI. The efficacy of Dotarem is expected to be demonstrated for at least 2 out of 3 readers independently meeting a statistically significant positive difference between the mean &quot;Paired&quot; score and the mean &quot;Pre&quot; score at patient level for each co primary endpoints.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy of enhanced MRI compared to unenhanced MRI</measure>
    <time_frame>24 - 48 hours</time_frame>
    <description>Efficacy of enhanced MRI compared to unenhanced MRI, based on (1) lesion counting, (2) signal intensity measurements, (3) image quality evaluation, and (4) diagnostic confidence (defined on 1-5 scale; 1= no confidence and 5 represents very high confidence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of adverse events (AEs)</measure>
    <time_frame>24 hours (+ / - 4 hours)</time_frame>
    <description>Assessment of adverse events (AEs), volunteered, observed or elicited by vital signs, physical examination, and continuous monitoring of AEs from the beginning of Dotarem injection until end of the follow-up period of 24 (+ / - 4) hours after contrast administration.</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">250</enrollment>
  <condition>Brain Diseases</condition>
  <arm_group>
    <arm_group_label>Dotarem Enhanced MRI</arm_group_label>
    <description>All pediatric patients (&lt; 18 years) scheduled for clinically indicated contrast enhanced MRI (Brain MRI with/without contrast) will receive a single IV bolus injection of Dotarem at a dose of 0.1 mmol/kg bw at a flow rate of 1-2 mL/sec followed by saline flush (routine/ standard of care).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dotarem</intervention_name>
    <description>Dotarem at dose of 0.1 mmol/kg of body weight (routine/standard of care)</description>
    <arm_group_label>Dotarem Enhanced MRI</arm_group_label>
    <other_name>gadoterate meglumine</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The study population will consist of N = 250 pediatric patients (&lt; 18 years) who are&#xD;
        indicated for contrast enhanced MRI.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Any patient under 18 years of age who is scheduled for contrast enhanced MRI&#xD;
             examination as part of their standard of care.&#xD;
&#xD;
          -  Patients who are willing to undergo contrast enhanced MRI procedure&#xD;
&#xD;
          -  Patients who are willing to comply with the study procedures (e.g. being followed-up&#xD;
             for 24 hours after MRI procedure).&#xD;
&#xD;
          -  Patients who have given their fully informed and written consent voluntarily.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients receiving an MRI exam without contrast.&#xD;
&#xD;
          -  Patients who are pregnant, lactating or who are &gt; 11 years old and have not had a&#xD;
             negative urine pregnancy test the same day as administration of Dotarem. The&#xD;
             manufacturer's instructions for performing the urinary pregnancy test are to be&#xD;
             followed.&#xD;
&#xD;
          -  Having an underlying disease or concomitant medication which may interfere with&#xD;
             efficacy or safety evaluations as planned in this study.&#xD;
&#xD;
          -  Patients with a Glomerular Filtration Rate (GFR) &lt; 30.&#xD;
&#xD;
          -  Having received any investigational drug within 30 days prior to entering this study&#xD;
             or who are planned to receive any investigational drug during the 24 (+ / - 4) hour&#xD;
             safety follow-up period.&#xD;
&#xD;
          -  Not being able to remain lying down for at least 45 - 60 min (e.g. patients with&#xD;
             unstable angina, dyspnea at rest, severe pain at rest, severe back pain).&#xD;
&#xD;
          -  Presenting with history of anaphylactoid or anaphylactic reaction to any allergen&#xD;
             including drugs and contrast agents .&#xD;
&#xD;
          -  Patients who have received any other contrast medium within 24 hours prior to Dotarem&#xD;
             injection or are scheduled to receive any other contrast medium within the follow-up&#xD;
             period.&#xD;
&#xD;
          -  Being clinically unstable and whose clinical course during the 24 (+ / - 4) hours&#xD;
             observation period is unpredictable.&#xD;
&#xD;
          -  Being scheduled for, or likely to require, any surgical intervention within 24 hours&#xD;
             before or within the follow-up period.&#xD;
&#xD;
          -  Having any contraindication to MRI examination (e.g. pacemaker, recent wound clips,&#xD;
             and severe claustrophobia).&#xD;
&#xD;
          -  Having been previously enrolled in this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeffrey H Miller, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Phoenix Children's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Phoenix Children's Hospital</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>January 12, 2017</study_first_submitted>
  <study_first_submitted_qc>January 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <last_update_submitted>May 18, 2022</last_update_submitted>
  <last_update_submitted_qc>May 18, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Phoenix Children's Hospital</investigator_affiliation>
    <investigator_full_name>Jeffrey Miller, MD</investigator_full_name>
    <investigator_title>Staff Physician, Vice Chair of Radiology</investigator_title>
  </responsible_party>
  <keyword>Dotarem</keyword>
  <keyword>MRI</keyword>
  <keyword>pediatric</keyword>
  <keyword>safety</keyword>
  <keyword>efficacy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate</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/NCT03023566
org study id: PCH IRB#16-102
nct id: NCT03023566
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
The goal of this study is to evaluate safety and efficacy of Dotarem enhanced MRI in
      pediatric and neonatal population who are referred for contrast enhanced MRI at Phoenix
      Children's Hospital.
Phoenix Children's Hospital (PCH) performs approximately 200 contrast enhanced MRI procedures
      per month. Recently PCH changed its MRI contrast agent from the linear contrast agent
      Magnevist to the macrocyclic contrast agent Dotarem. The goal of this study is to evaluate
      safety and efficacy of Dotarem enhanced MRI in pediatric and neonatal population who are
      referred for contrast enhanced MRI at PCH.

      The study is designed as a single center, open label comparison of unenhanced MRI with
      Dotarem enhanced MRI in pediatric patient population (<18years). The comparison will be
      performed intra-individually by 3 independent blinded radiologists. Overall, the study
      population will consist of 250 pediatric patients who are indicated for contrast enhanced
      MRI. The safety follow-up period will be 24 (+/- 4) hours post injection of Dotarem and
      includes the assessment of physical examinations and vital signs as well as the assessment of
      AEs.
observational model: Cohort
time perspective: Prospective
measure: Overall lesion visualization and characterization
time frame: 24 - 48 hours
description: Overall lesion visualization and characterization, based on assessment of (1) lesion border delineation, (2) internal morphology and (3) degree of contrast enhancement. All images from "Pre" (unenhanced MRI) and "Paired" (unenhanced + enhanced) MRI will be evaluated independently by the 3 independent readers and are rated on a 3-point scale as unevaluable (0), seen but imperfectly (1) or seen completely/perfectly (2). The primary statistical analysis compared unenhanced MRI to combined MRI. The efficacy of Dotarem is expected to be demonstrated for at least 2 out of 3 readers independently meeting a statistically significant positive difference between the mean "Paired" score and the mean "Pre" score at patient level for each co primary endpoints.
measure: Efficacy of enhanced MRI compared to unenhanced MRI
time frame: 24 - 48 hours
description: Efficacy of enhanced MRI compared to unenhanced MRI, based on (1) lesion counting, (2) signal intensity measurements, (3) image quality evaluation, and (4) diagnostic confidence (defined on 1-5 scale; 1= no confidence and 5 represents very high confidence
measure: Assessment of adverse events (AEs)
time frame: 24 hours (+ / - 4 hours)
description: Assessment of adverse events (AEs), volunteered, observed or elicited by vital signs, physical examination, and continuous monitoring of AEs from the beginning of Dotarem injection until end of the follow-up period of 24 (+ / - 4) hours after contrast administration.
arm group label: Dotarem Enhanced MRI
description: All pediatric patients (< 18 years) scheduled for clinically indicated contrast enhanced MRI (Brain MRI with/without contrast) will receive a single IV bolus injection of Dotarem at a dose of 0.1 mmol/kg bw at a flow rate of 1-2 mL/sec followed by saline flush (routine/ standard of care).
intervention type: Drug
intervention name: Dotarem
description: Dotarem at dose of 0.1 mmol/kg of body weight (routine/standard of care)
arm group label: Dotarem Enhanced MRI
other name: gadoterate meglumine
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: 18 Years
healthy volunteers: No
last name: Jeffrey H Miller, MD
role: Principal Investigator
affiliation: Phoenix Children's Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Phoenix Children's Hospital
investigator full name: Jeffrey Miller, MD
investigator title: Staff Physician, Vice Chair of Radiology
mesh term: Brain Diseases
mesh term: Gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
sharing ipd: No