<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/NCT03002558</url>
  </required_header>
  <id_info>
    <org_study_id>SARAH-1</org_study_id>
    <nct_id>NCT03002558</nct_id>
  </id_info>
  <brief_title>Long-term Cardiovascular Outcomes in Patients With RH and OSA With or Without Treatment With CPAP</brief_title>
  <acronym>SARAH</acronym>
  <official_title>Long-term Cardiovascular Outcomes in Patients With Resistant Hypertension and Obstructive Sleep Apnea With or Without Treatment With Continuous Positive Airway Pressure.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sociedad Española de Neumología y Cirugía Torácica</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fondo de Investigacion Sanitaria</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>ResMed</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Sociedad Española de Neumología y Cirugía Torácica</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Objectives:&#xD;
&#xD;
      Main objective: To assess the impact of obstructive sleep apnea (OSA) and its treatment on&#xD;
      cardiovascular outcomes (morbidity and mortality) in patients with resistant hypertension&#xD;
      (RH).&#xD;
&#xD;
      Secondary objectives: i) to identify the subclinical organ damage profile at baseline and its&#xD;
      association with OSA, and to identify if long term blood pressure control and number of&#xD;
      antihypertensive drugs needed is different depending on OSA diagnosis and its treatment; ii)&#xD;
      to identify epigenetic profiles and clinical, biological and polygraphic variables with a&#xD;
      predictive value for cardiovascular outcomes in RH patients with OSA; iii) to validate the&#xD;
      HIPARCO-SCORE tool in men in an independent cohort and elaborate a new tool to be used in&#xD;
      women; and iv) to perform a cost-effectiveness analysis to evaluate the impact of OSA&#xD;
      diagnosis and treatment in patients with RH.&#xD;
&#xD;
      Methodology: Prospective cohort study. 1,371 RH patients will be recruited. Ambulatory blood&#xD;
      pressure monitoring (ABPM), socio-demographic, clinical, OSA-related, biochemical and&#xD;
      subclinical organ damage variables and biological samples at baseline will be collected from&#xD;
      all the subjects included. A sleep study will be performed in all the subjects at the study&#xD;
      inclusion date. Subsequently, the OSA subjects will be managed as per local standard&#xD;
      practice. Follow-up variables will be annually collected (including blood samples). On the&#xD;
      basis of OSA and its treatment, three cohorts of RH subjects will be defined: control&#xD;
      (non-OSA), OSA-treated and OSA nontreated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A minimum follow-up of 5 years has been established. During the follow-up, an annually&#xD;
      programmed visit will be carried on to all patients, collecting variables from subjects'&#xD;
      interview in the office.The baseline and follow-up variables will be collected using&#xD;
      questionnaires.&#xD;
&#xD;
      The variables that will be collected are:&#xD;
&#xD;
      BP variables; Anthropometric variables; Compliance with CPAP in the case of CPAP-treated OSA&#xD;
      patients; blood samples extraction; outcomes (heart disease, cerebrovascular disease, kidney&#xD;
      disease, vascular disease). All the cardiovascular events will be independently evaluated by&#xD;
      two doctors to establish a diagnostic. In case of discordance a third external doctor will&#xD;
      assess the case. The date of each event will be recorded.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 29, 2016</start_date>
  <completion_date type="Anticipated">June 2023</completion_date>
  <primary_completion_date type="Anticipated">June 2023</primary_completion_date>
  <study_type>Observational [Patient Registry]</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>
  <target_duration>5 Years</target_duration>
  <primary_outcome>
    <measure>Evaluation the impact of OSA and its treatment on cardiovascular outcomes</measure>
    <time_frame>After 5 years of follow-up</time_frame>
    <description>OSA diagnosis shall be established by PSG or PCR. It will be evaluated cardiovascular outcomes (CV death, non-fatal acute myocardial infarction, non-fatal stroke, hospital admission for heart failure and new hospitalization for unstable angina or Transitory Ischemic Attack) before and after of OSA diagnosis and treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cardiovascular composite: CV death, non-fatal acute myocardial infarction, non-fatal stroke, hospital admission for heart failure and new hospitalization for unstable angina or Transitory Ischemic Attack.</measure>
    <time_frame>After 5 years of follow-up</time_frame>
    <description>It will be evaluated cardiovascular outcomes at the end of the study. These outcomes will be collected from subjects' interviews at each yearly follow-up visit in the office and from computed medical records.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Identify epigenetic biomarkers signatures with a predictive value of favourable cardiovascular outcome in patients with RH.</measure>
    <time_frame>After 5 years of follow-up</time_frame>
    <description>Using DNA and RNA samples, it will be performed different analysis at the end of the study, to see if there is any change in genes related to both diseases</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Validation the HIPARCO - Score tool in an independent cohort, men with resistant hypertension, OSA and CPAP compliance (≥4h/night)</measure>
    <time_frame>2 years</time_frame>
    <description>Analyse mRNA to validate de HIPARCO score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Creation of a predictive tool (like HIPARCO-Score) for women</measure>
    <time_frame>3 years</time_frame>
    <description>Identify a plasma miRNA profile that predicts blood pressure response to CPAP treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost- Effectiveness analyses between study groups and to compare the cost of health care utilization between two year before and after the starting of the study related to the study groups.</measure>
    <time_frame>After 5 years of follow-up</time_frame>
    <description>Only direct costs will be considered. Analysis will include an estimation of quality-adjusted life-years (QALYs) gained</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">1371</enrollment>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>control (non-OSA)</arm_group_label>
    <description>Patients without sleep apnoea</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OSA-treated</arm_group_label>
    <description>Patients with sleep apnoea who are treated (CPAP, surgery or MAD)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>OSA-non treated</arm_group_label>
    <description>Patients with sleep apnoea who are not treated</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      -  2 tubes EDTA&#xD;
&#xD;
        -  2 tubes with gel for serum&#xD;
&#xD;
        -  1 tube for RNA extraction&#xD;
&#xD;
        -  1 tube for urine&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with Resistant Hypertension&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients diagnosed of RH according to the following criteria, which include 2 clinical&#xD;
             situations: (i) BP above control in ABPM (24-h BP &gt; 130/80 mmHg),regardless of optimal&#xD;
             dose treatment with 3 agents (one must be a diuretic). Other causes of inadequate&#xD;
             control must be discarded (poor compliance, drugs). (ii) Controlled BP but treated&#xD;
             with no less than 4 medications.&#xD;
&#xD;
          -  Patients aged 18 to 75 years old.&#xD;
&#xD;
          -  To sign informed consent for the participation in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Secondary hypertension to endocrinology causes (pheochromocytoma, Conn disease,&#xD;
             Cushing´s Syndrome, hyperparathyroidism), drug treatment (NSAID or cortisone,&#xD;
             immunodepressants, EPO), renal artery stenosis, alcohol abuse, aortic coarctation and&#xD;
             intracranial tumours.&#xD;
&#xD;
          -  Any process, that limits life expectancy to less than one year.&#xD;
&#xD;
          -  Previously diagnosed OSA with current active treatment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ferran Barbé</last_name>
    <role>Principal Investigator</role>
    <affiliation>Spanish Respiratory Society (SEPAR)</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ferran Barbé, MD</last_name>
    <phone>34973705372</phone>
    <email>febarbe.lleida.ics@gencat.cat</email>
  </overall_contact>
  <location>
    <facility>
      <name>Spanish Respiratory Society</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ferran Barbe, MD</last_name>
      <phone>349733705372</phone>
      <email>febarbe.lleida.ics@gencat.cat</email>
    </contact>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>December 16, 2016</study_first_submitted>
  <study_first_submitted_qc>December 20, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 23, 2016</study_first_posted>
  <last_update_submitted>March 19, 2021</last_update_submitted>
  <last_update_submitted_qc>March 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 22, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sociedad Española de Neumología y Cirugía Torácica</investigator_affiliation>
    <investigator_full_name>Ferran Barbe</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>Hypertension</keyword>
  <keyword>Continuous Positive Airway Pressure</keyword>
  <keyword>Obstructive Sleep Apnea</keyword>
  <keyword>Cardiovascular Diseases</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
  </condition_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/NCT03002558
org study id: SARAH-1
nct id: NCT03002558
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Objectives:

      Main objective: To assess the impact of obstructive sleep apnea (OSA) and its treatment on
      cardiovascular outcomes (morbidity and mortality) in patients with resistant hypertension
      (RH).

      Secondary objectives: i) to identify the subclinical organ damage profile at baseline and its
      association with OSA, and to identify if long term blood pressure control and number of
      antihypertensive drugs needed is different depending on OSA diagnosis and its treatment; ii)
      to identify epigenetic profiles and clinical, biological and polygraphic variables with a
      predictive value for cardiovascular outcomes in RH patients with OSA; iii) to validate the
      HIPARCO-SCORE tool in men in an independent cohort and elaborate a new tool to be used in
      women; and iv) to perform a cost-effectiveness analysis to evaluate the impact of OSA
      diagnosis and treatment in patients with RH.

      Methodology: Prospective cohort study. 1,371 RH patients will be recruited. Ambulatory blood
      pressure monitoring (ABPM), socio-demographic, clinical, OSA-related, biochemical and
      subclinical organ damage variables and biological samples at baseline will be collected from
      all the subjects included. A sleep study will be performed in all the subjects at the study
      inclusion date. Subsequently, the OSA subjects will be managed as per local standard
      practice. Follow-up variables will be annually collected (including blood samples). On the
      basis of OSA and its treatment, three cohorts of RH subjects will be defined: control
      (non-OSA), OSA-treated and OSA nontreated.
A minimum follow-up of 5 years has been established. During the follow-up, an annually
      programmed visit will be carried on to all patients, collecting variables from subjects'
      interview in the office.The baseline and follow-up variables will be collected using
      questionnaires.

      The variables that will be collected are:

      BP variables; Anthropometric variables; Compliance with CPAP in the case of CPAP-treated OSA
      patients; blood samples extraction; outcomes (heart disease, cerebrovascular disease, kidney
      disease, vascular disease). All the cardiovascular events will be independently evaluated by
      two doctors to establish a diagnostic. In case of discordance a third external doctor will
      assess the case. The date of each event will be recorded.
observational model: Cohort
time perspective: Prospective
measure: Evaluation the impact of OSA and its treatment on cardiovascular outcomes
time frame: After 5 years of follow-up
description: OSA diagnosis shall be established by PSG or PCR. It will be evaluated cardiovascular outcomes (CV death, non-fatal acute myocardial infarction, non-fatal stroke, hospital admission for heart failure and new hospitalization for unstable angina or Transitory Ischemic Attack) before and after of OSA diagnosis and treatment.
measure: Cardiovascular composite: CV death, non-fatal acute myocardial infarction, non-fatal stroke, hospital admission for heart failure and new hospitalization for unstable angina or Transitory Ischemic Attack.
time frame: After 5 years of follow-up
description: It will be evaluated cardiovascular outcomes at the end of the study. These outcomes will be collected from subjects' interviews at each yearly follow-up visit in the office and from computed medical records.
measure: Identify epigenetic biomarkers signatures with a predictive value of favourable cardiovascular outcome in patients with RH.
time frame: After 5 years of follow-up
description: Using DNA and RNA samples, it will be performed different analysis at the end of the study, to see if there is any change in genes related to both diseases
measure: Validation the HIPARCO - Score tool in an independent cohort, men with resistant hypertension, OSA and CPAP compliance (≥4h/night)
time frame: 2 years
description: Analyse mRNA to validate de HIPARCO score
measure: Creation of a predictive tool (like HIPARCO-Score) for women
time frame: 3 years
description: Identify a plasma miRNA profile that predicts blood pressure response to CPAP treatment.
measure: Cost- Effectiveness analyses between study groups and to compare the cost of health care utilization between two year before and after the starting of the study related to the study groups.
time frame: After 5 years of follow-up
description: Only direct costs will be considered. Analysis will include an estimation of quality-adjusted life-years (QALYs) gained
arm group label: control (non-OSA)
description: Patients without sleep apnoea
arm group label: OSA-treated
description: Patients with sleep apnoea who are treated (CPAP, surgery or MAD)
arm group label: OSA-non treated
description: Patients with sleep apnoea who are not treated
-  2 tubes EDTA

        -  2 tubes with gel for serum

        -  1 tube for RNA extraction

        -  1 tube for urine
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Ferran Barbé
role: Principal Investigator
affiliation: Spanish Respiratory Society (SEPAR)
last name: Ferran Barbé, MD
phone: 34973705372
email: febarbe.lleida.ics@gencat.cat
facility: 
status: Recruiting
contact: 
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Sociedad Española de Neumología y Cirugía Torácica
investigator full name: Ferran Barbe
investigator title: MD
mesh term: Hypertension
sharing ipd: Undecided