<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/NCT03249285</url>
  </required_header>
  <id_info>
    <org_study_id>udraCT NUMBER: 2015-001888-39</org_study_id>
    <nct_id>NCT03249285</nct_id>
  </id_info>
  <brief_title>Pharmacogenomics of Hypertension Personalized Medicine (PGX-HT)</brief_title>
  <acronym>PGX-HT</acronym>
  <official_title>Pharmacogenomics Of Hypertension: A New Approach For A Personalized Medicine</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ospedale San Raffaele</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ospedale San Raffaele</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pharmacogenomic prospective , four-arms, parallel groups, active comparator&#xD;
      controlled study in essential hypertensive patients never treated before.&#xD;
&#xD;
      Each patient will be genotyped for SNPs (single nucleotide polymorphism) in preliminary&#xD;
      genetic profiles and will be treated according to their genetic profile with Peri&#xD;
      (Perindopril) 4 mg or HCTZ ( hydrochlorothiazide) 12.5 mg.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      At screening visit each patient will be genotyped for SNPs in preliminary genetic profiles&#xD;
      with a custom SNP array.&#xD;
&#xD;
      The therapy scheme includes 2-4-week run-in period after which eligible patients will be&#xD;
      treated according to their genetic profile with Peri 4 mg or HCTZ 12.5 mg. Titration to Peri&#xD;
      8 mg or HCTZ 25 mg could be possible after one month treatment.&#xD;
&#xD;
      Patients without any genetic profile will be randomly assigned to HCTZ or Peri treatment as&#xD;
      control groups.&#xD;
&#xD;
      The treatment period will last 8 weeks, while the study about 10-12 weeks&#xD;
&#xD;
      Four cases may occur:&#xD;
&#xD;
        -  patient with HCTZ profile, HCTZ treatment;&#xD;
&#xD;
        -  patient with Peri profile, Peri treatment;&#xD;
&#xD;
        -  patient without HCTZ nor Peri profile, randomization for HCTZ or Peri;&#xD;
&#xD;
        -  patient with both profiles, treatment according to the profile with the higher number of&#xD;
           positive contributors.&#xD;
&#xD;
      Eligible patients will be treated according to their genetic profile with Peri 4 mg or HCTZ&#xD;
      12.5 mg/die.&#xD;
&#xD;
      Titration to Peri 8 mg or HCTZ 25 mg could be possible after 4 weeks treatment. The treatment&#xD;
      period will last 8 weeks, while the study about 10-12 weeks&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>March 2016</start_date>
  <completion_date type="Anticipated">November 2018</completion_date>
  <primary_completion_date type="Anticipated">March 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>SBP (Systolic blood pressure) and DBP (Diastolic blood pressure) response</measure>
    <time_frame>4 and 8 weeks</time_frame>
    <description>Difference in SBP and DBP variation after 4 and 8 weeks of therapy according to the presence or not of specific genetic profile for each drugs</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Profiles implementation</measure>
    <time_frame>in the three months after the end of the study</time_frame>
    <description>Implementing and redefining the genetic profile for HCTZ or/and Peri by using a further spectrum of 128 different SNP variants</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Peri profile yes</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patient with genetic Perindopril profile, receiving Perindopril treatment with 4-8 mg/day oral for 4-8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HCTZ profile yes</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patient with genetic HCTZ profile, receiving HCTZ treatment with 12,5-25 mg/day oral for 4-8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Peri no profile</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>patient with no genetic profile, receiving after randomisation Perindopril treatment with 4-8 mg/day oral for 4-8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HCTZ no profile</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>patient with no genetic profile, receiving after randomisation HCTZ treatment with 12,5-25 mg/day oral for 4-8 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Peri</intervention_name>
    <description>Perindopril 4 mg /day, orally with titration to 8 mg/day after 1 month if BP (Blood pressure) is not controlled</description>
    <arm_group_label>Peri no profile</arm_group_label>
    <arm_group_label>Peri profile yes</arm_group_label>
    <other_name>Perindopril</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HCTZ</intervention_name>
    <description>Hydrochlorothiazide 12, 5 mg day, orally with titration to 25 mg/day after 1 month if BP is not controlled</description>
    <arm_group_label>HCTZ no profile</arm_group_label>
    <arm_group_label>HCTZ profile yes</arm_group_label>
    <other_name>Hydrochlorothiazide</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male/Female patients aged 25-60 years.&#xD;
&#xD;
          -  Naive hypertensive patients (newly diagnosed, never treated before).&#xD;
&#xD;
          -  Documented mild to moderate arterial hypertension, as defined below:&#xD;
&#xD;
               1. At Visits 1 and 2 (week -4 and week -2 run-in period) the mean of the last 3&#xD;
                  consecutive readings of office SBP must be &gt;= 140 mmHg and/or DBP must be &gt;=90&#xD;
                  mmHg, when measured by office blood pressure (OBP);&#xD;
&#xD;
               2. At Visit 3 (week 0) enrolment , the mean of the last 3 consecutive readings of&#xD;
                  SBP must be &gt;= 140 mmHg and &lt;160 mmHg, and DBP must be &gt;= 90 mmHg and &lt;110 mmHg,&#xD;
                  when measured by OBP.&#xD;
&#xD;
          -  Signed informed consent for genotyping.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  known causes of secondary hypertension;&#xD;
&#xD;
          -  pregnant, nursing women or women of childbearing potential taking anti-contraceptive&#xD;
             medication;&#xD;
&#xD;
          -  severe or malignant hypertension;&#xD;
&#xD;
          -  history of renal artery disease;&#xD;
&#xD;
          -  significant renal disease (estimated creatinine clearance less than 60 mL/min);&#xD;
&#xD;
          -  hepatic disease;&#xD;
&#xD;
          -  cardiac diseases (myocardial infarction, atrial fibrillation, etc);&#xD;
&#xD;
          -  diabetes (fasting plasma glucose &gt;125mg/dL);&#xD;
&#xD;
          -  statin treatment;&#xD;
&#xD;
          -  obesity (BMI&gt;30 kg/m2).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Manunta Paolo, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>Scientif Institute San Raffale</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Lanzani Chiara, Doctor</last_name>
    <phone>+390226435330</phone>
    <email>lanzani.chiara@hsr.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Brioni Elena, Nurse</last_name>
    <phone>+390226432876</phone>
    <email>brioni.elena@hsr.it</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Azienda Sanitaria 6</name>
      <address>
        <city>Livorno</city>
        <zip>57121</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Bigazzi Roberto</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>San Raffaele Hospital</name>
      <address>
        <city>Milan</city>
        <zip>20131</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lanzani L Chiara, Doctor</last_name>
      <phone>+390226435330</phone>
      <email>lanzani.chiara@hsr.it</email>
    </contact>
    <contact_backup>
      <last_name>Brioni Elena, Nurse</last_name>
      <phone>+390226432876</phone>
      <email>brioni.elena@hsr.it</email>
    </contact_backup>
    <investigator>
      <last_name>Simonini Marco, Doctor</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Tentori Stefano, Doctor</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero - Universitaria S. Maria della Misericordia</name>
      <address>
        <city>Udine</city>
        <zip>33170</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Leonardo A Sechi</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>February 13, 2017</study_first_submitted>
  <study_first_submitted_qc>August 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>August 10, 2017</last_update_submitted>
  <last_update_submitted_qc>August 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ospedale San Raffaele</investigator_affiliation>
    <investigator_full_name>Chiara Lanzani</investigator_full_name>
    <investigator_title>medical doctor</investigator_title>
  </responsible_party>
  <keyword>hypertension</keyword>
  <keyword>pharmacogenomics</keyword>
  <keyword>anti-hypertensive therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydrochlorothiazide</mesh_term>
    <mesh_term>Perindopril</mesh_term>
  </intervention_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/NCT03249285
org study id: udraCT NUMBER: 2015-001888-39
nct id: NCT03249285
lead sponsor: 
has dmc: Yes
This is a pharmacogenomic prospective , four-arms, parallel groups, active comparator
      controlled study in essential hypertensive patients never treated before.

      Each patient will be genotyped for SNPs (single nucleotide polymorphism) in preliminary
      genetic profiles and will be treated according to their genetic profile with Peri
      (Perindopril) 4 mg or HCTZ ( hydrochlorothiazide) 12.5 mg.
At screening visit each patient will be genotyped for SNPs in preliminary genetic profiles
      with a custom SNP array.

      The therapy scheme includes 2-4-week run-in period after which eligible patients will be
      treated according to their genetic profile with Peri 4 mg or HCTZ 12.5 mg. Titration to Peri
      8 mg or HCTZ 25 mg could be possible after one month treatment.

      Patients without any genetic profile will be randomly assigned to HCTZ or Peri treatment as
      control groups.

      The treatment period will last 8 weeks, while the study about 10-12 weeks

      Four cases may occur:

        -  patient with HCTZ profile, HCTZ treatment;

        -  patient with Peri profile, Peri treatment;

        -  patient without HCTZ nor Peri profile, randomization for HCTZ or Peri;

        -  patient with both profiles, treatment according to the profile with the higher number of
           positive contributors.

      Eligible patients will be treated according to their genetic profile with Peri 4 mg or HCTZ
      12.5 mg/die.

      Titration to Peri 8 mg or HCTZ 25 mg could be possible after 4 weeks treatment. The treatment
      period will last 8 weeks, while the study about 10-12 weeks
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: SBP (Systolic blood pressure) and DBP (Diastolic blood pressure) response
time frame: 4 and 8 weeks
description: Difference in SBP and DBP variation after 4 and 8 weeks of therapy according to the presence or not of specific genetic profile for each drugs
measure: Profiles implementation
time frame: in the three months after the end of the study
description: Implementing and redefining the genetic profile for HCTZ or/and Peri by using a further spectrum of 128 different SNP variants
arm group label: Peri profile yes
arm group type: Experimental
description: patient with genetic Perindopril profile, receiving Perindopril treatment with 4-8 mg/day oral for 4-8 weeks
arm group label: HCTZ profile yes
arm group type: Experimental
description: patient with genetic HCTZ profile, receiving HCTZ treatment with 12,5-25 mg/day oral for 4-8 weeks
arm group label: Peri no profile
arm group type: Active Comparator
description: patient with no genetic profile, receiving after randomisation Perindopril treatment with 4-8 mg/day oral for 4-8 weeks
arm group label: HCTZ no profile
arm group type: Active Comparator
description: patient with no genetic profile, receiving after randomisation HCTZ treatment with 12,5-25 mg/day oral for 4-8 weeks
intervention type: Drug
intervention name: Peri
description: Perindopril 4 mg /day, orally with titration to 8 mg/day after 1 month if BP (Blood pressure) is not controlled
arm group label: Peri no profile
arm group label: Peri profile yes
other name: Perindopril
intervention type: Drug
intervention name: HCTZ
description: Hydrochlorothiazide 12, 5 mg day, orally with titration to 25 mg/day after 1 month if BP is not controlled
arm group label: HCTZ no profile
arm group label: HCTZ profile yes
other name: Hydrochlorothiazide
criteria: 
gender: All
minimum age: 25 Years
maximum age: 60 Years
healthy volunteers: No
last name: Manunta Paolo, Professor
role: Study Chair
affiliation: Scientif Institute San Raffale
last name: Lanzani Chiara, Doctor
phone: +390226435330
email: lanzani.chiara@hsr.it
last name: Brioni Elena, Nurse
phone: +390226432876
email: brioni.elena@hsr.it
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
facility: 
status: Not yet recruiting
contact: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: Ospedale San Raffaele
investigator full name: Chiara Lanzani
investigator title: medical doctor
mesh term: Hypertension
mesh term: Hydrochlorothiazide
mesh term: Perindopril
sharing ipd: Undecided