<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/NCT04480723</url>
  </required_header>
  <id_info>
    <org_study_id>CR108827</org_study_id>
    <secondary_id>NAPUH0003</secondary_id>
    <nct_id>NCT04480723</nct_id>
  </id_info>
  <brief_title>A Study for the Identification of Biomarker Signatures for Diagnosis of Pulmonary Hypertension (PH) in Participants at Low or Intermediate Probability of PH Undergoing Cardiac Magnetic Resonance Imaging</brief_title>
  <official_title>A Prospective Multicenter Study for the Assessment of Biomarker Signatures for the Diagnosis of Pulmonary Hypertension (PH) in Patients at Low or Intermediate Probability of PH Undergoing Cardiac Magnetic Resonance Imaging (MRI) CIPHER-MRI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Actelion</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Actelion</source>
  <oversight_info>
    <has_dmc>No</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 primary purpose of this study is to estimate the percentage of participants in the&#xD;
      population considered clinically as not having pulmonary hypertension (PH) that are positive&#xD;
      for PH biomarker (micro ribonucleic acid [RNA]); estimate the percentage of participants in&#xD;
      the population considered clinically as not having PH that are positive for PH by cardiac&#xD;
      magnetic resonance imaging (MRI) and compare results of the MRI to the biomarker results; to&#xD;
      determine the performance of the biomarker signatures identified in the CIPHER (NAPUH0001)&#xD;
      study in terms of sensitivity, specificity, positive predictive value (PPV) and negative&#xD;
      predictive value (NPV), in a population considered clinically as not having PH.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 11, 2020</start_date>
  <completion_date type="Actual">May 18, 2022</completion_date>
  <primary_completion_date type="Actual">May 13, 2022</primary_completion_date>
  <phase>Early Phase 1</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>Percentage of Participants in the Population Considered Clinically as not Having PH that are Positive for PH Biomarker</measure>
    <time_frame>Up to 90 Days</time_frame>
    <description>Percentage of (transthoracic echocardiography [TTE] low/intermediate probability) participants who are positive for the biomarker will be estimated.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants Considered Clinically as not Having PH that are Positive for PH by Cardiac MRI</measure>
    <time_frame>Up to 90 Days</time_frame>
    <description>Percentage of participants considered clinically as not having PH that are positive for PH by cardiac magnetic resonance imaging (MRI) will be evaluated.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Performance of Biomarker Results</measure>
    <time_frame>Up to 90 Days</time_frame>
    <description>The performance of the biomarker in the diagnosis of PH will be evaluated using the MRI result.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Performance of the Biomarker Signatures Identified in the CIPHER Study in Terms of Sensitivity, specificity, positive predictive value (PPV) and Negative Predictive Value (NPV), in Participants not Having PH</measure>
    <time_frame>Up to 90 Days</time_frame>
    <description>Performance of the biomarker signatures identified in the CIPHER study in terms of sensitivity, specificity, PPV and NPV, in a population considered clinically as not having PH will be estimated.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Biomarker Data Pooled with the Biomarker Data Collected from the CIPHER (NAPUH0001) Study</measure>
    <time_frame>Up to 90 Days</time_frame>
    <description>The biomarker data collected from participants with low/intermediate suspicion of PH in the CIPHER-MRI study will be pooled with the data collected from the high to intermediate suspicion of PH participants in the CIPHER (NAPUH0001) study to evaluate the performance of the biomarker signature(s) developed in CIPHER (NAPUH0001).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">86</enrollment>
  <condition>Hypertension, Pulmonary</condition>
  <arm_group>
    <arm_group_label>Participants with Low or Intermediate Probability of PH</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants who underwent a work-up for the suspicion of PH that includes transthoracic echocardiography (TTE) and who were considered to have a low or intermediate probability of PH according to TTE (local interpretation) will be enrolled. Blood samples will be taken and a cardiac magnetic resonance imaging (MRI) will be performed to evaluate the presence of Pulmonary Hypertension (PH). The TTEs that were performed by local standards will be collected and undergo central interpretation using European society of Cardiology / European respiratory society (ESC/ERS) guidelines to confirm the local interpretation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Blood Sample</intervention_name>
    <description>Blood samples will be taken and analyzed to evaluate the presence of PH.</description>
    <arm_group_label>Participants with Low or Intermediate Probability of PH</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Cardiac MRI</intervention_name>
    <description>Cardiac MRI will be performed to evaluate the presence of PH.</description>
    <arm_group_label>Participants with Low or Intermediate Probability of PH</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Referred for diagnostic work-up for pulmonary hypertension (PH)&#xD;
&#xD;
          -  With low or intermediate (but not high) probability of PH by transthoracic&#xD;
             echocardiography (TTE) according to European Society of Cardiology (ESC)/ European&#xD;
             Respiratory Society (ERS) Guidelines if at the time of enrollment Right Heart&#xD;
             Catheterization (RHC) is not deemed to be clinically indicated&#xD;
&#xD;
          -  Medically stable on the basis of physical examination, medical history and vital signs&#xD;
             performed at screening. Any abnormalities must be consistent with the underlying&#xD;
             illness in the study population and this determination must be recorded in the&#xD;
             participant's source documents and initialed by the investigator&#xD;
&#xD;
          -  Must sign an Informed consent (ICF) indicating that he or she understands the purpose&#xD;
             of, and procedures required for, the study and is willing to participate in the study&#xD;
&#xD;
          -  Must sign a separate approval in the ICF if he or she agrees to provide an optional&#xD;
             (DNA) sample for research. Refusal to give consent for the optional (DNA) research&#xD;
             sample does not exclude a participant from participation in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Undergone RHC within 2 years&#xD;
&#xD;
          -  Participants requiring renal dialysis&#xD;
&#xD;
          -  Participants post-lung or heart transplant&#xD;
&#xD;
          -  Severe left ventricular dysfunction: left ventricular ejection fraction less then (&lt;)&#xD;
             35 percent&#xD;
&#xD;
          -  Ongoing Contagious respiratory disease&#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>Actelion Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Actelion</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Universitatsklinikum Bonn</name>
      <address>
        <city>Bonn</city>
        <zip>53105</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Giessen</name>
      <address>
        <city>Giessen</city>
        <zip>35392</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Schleswig-Holstein</name>
      <address>
        <city>Luebeck</city>
        <zip>23538</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal United Hospital</name>
      <address>
        <city>Bath</city>
        <zip>BA1 3NG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Waiting Times Centre Board Golden Jubilee National Hospital</name>
      <address>
        <city>Glasgow</city>
        <zip>G81 4DY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Free Hospital</name>
      <address>
        <city>London</city>
        <zip>NW3 2QG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hammersmith Hospital</name>
      <address>
        <city>London</city>
        <zip>W12 0HS</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital</name>
      <address>
        <city>Sheffield</city>
        <zip>S10 2RX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 17, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>August 16, 2022</last_update_submitted>
  <last_update_submitted_qc>August 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 17, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension, Pulmonary</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The data sharing policy of the Janssen Pharmaceutical Companies of Johnson &amp; Johnson is available at www.janssen.com/clinical-trials/transparency.&#xD;
As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu</ipd_description>
    <ipd_url>https://www.janssen.com/clinical-trials/transparency</ipd_url>
  </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/NCT04480723
org study id: CR108827
secondary id: NAPUH0003
nct id: NCT04480723
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary purpose of this study is to estimate the percentage of participants in the
      population considered clinically as not having pulmonary hypertension (PH) that are positive
      for PH biomarker (micro ribonucleic acid [RNA]); estimate the percentage of participants in
      the population considered clinically as not having PH that are positive for PH by cardiac
      magnetic resonance imaging (MRI) and compare results of the MRI to the biomarker results; to
      determine the performance of the biomarker signatures identified in the CIPHER (NAPUH0001)
      study in terms of sensitivity, specificity, positive predictive value (PPV) and negative
      predictive value (NPV), in a population considered clinically as not having PH.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Percentage of Participants in the Population Considered Clinically as not Having PH that are Positive for PH Biomarker
time frame: Up to 90 Days
description: Percentage of (transthoracic echocardiography [TTE] low/intermediate probability) participants who are positive for the biomarker will be estimated.
measure: Percentage of Participants Considered Clinically as not Having PH that are Positive for PH by Cardiac MRI
time frame: Up to 90 Days
description: Percentage of participants considered clinically as not having PH that are positive for PH by cardiac magnetic resonance imaging (MRI) will be evaluated.
measure: Performance of Biomarker Results
time frame: Up to 90 Days
description: The performance of the biomarker in the diagnosis of PH will be evaluated using the MRI result.
measure: Performance of the Biomarker Signatures Identified in the CIPHER Study in Terms of Sensitivity, specificity, positive predictive value (PPV) and Negative Predictive Value (NPV), in Participants not Having PH
time frame: Up to 90 Days
description: Performance of the biomarker signatures identified in the CIPHER study in terms of sensitivity, specificity, PPV and NPV, in a population considered clinically as not having PH will be estimated.
measure: Biomarker Data Pooled with the Biomarker Data Collected from the CIPHER (NAPUH0001) Study
time frame: Up to 90 Days
description: The biomarker data collected from participants with low/intermediate suspicion of PH in the CIPHER-MRI study will be pooled with the data collected from the high to intermediate suspicion of PH participants in the CIPHER (NAPUH0001) study to evaluate the performance of the biomarker signature(s) developed in CIPHER (NAPUH0001).
arm group label: Participants with Low or Intermediate Probability of PH
arm group type: Other
description: Participants who underwent a work-up for the suspicion of PH that includes transthoracic echocardiography (TTE) and who were considered to have a low or intermediate probability of PH according to TTE (local interpretation) will be enrolled. Blood samples will be taken and a cardiac magnetic resonance imaging (MRI) will be performed to evaluate the presence of Pulmonary Hypertension (PH). The TTEs that were performed by local standards will be collected and undergo central interpretation using European society of Cardiology / European respiratory society (ESC/ERS) guidelines to confirm the local interpretation.
intervention type: Other
intervention name: Blood Sample
description: Blood samples will be taken and analyzed to evaluate the presence of PH.
arm group label: Participants with Low or Intermediate Probability of PH
intervention type: Diagnostic Test
intervention name: Cardiac MRI
description: Cardiac MRI will be performed to evaluate the presence of PH.
arm group label: Participants with Low or Intermediate Probability of PH
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Actelion Clinical Trial
role: Study Director
affiliation: Actelion
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
country: United Kingdom
responsible party type: Sponsor
mesh term: Hypertension, Pulmonary
mesh term: Hypertension
sharing ipd: Yes
ipd description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.
As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
ipd url: https://www.janssen.com/clinical-trials/transparency