<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/NCT04457505</url>
  </required_header>
  <id_info>
    <org_study_id>CIBERESUCICOVID</org_study_id>
    <nct_id>NCT04457505</nct_id>
  </id_info>
  <brief_title>One Year Follow-ups of Patients Admitted to Spanish Intensive Care Units Due to COVID-19</brief_title>
  <official_title>Risk Factors, Personalized Prognoses and 1-year Follow-ups of Patients Admitted to Spanish Intensive Care Units Due to COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Consorcio Centro de Investigación Biomédica en Red (CIBER)</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Barcelona Supercomputing Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Carlos III Health Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Consorcio Centro de Investigación Biomédica en Red (CIBER)</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 latest epidemiological data published from Chine reports that up to 30% of&#xD;
      hospital-admitted patients required admission to intensive care units (ICU). The cause for&#xD;
      ICU admission for most patients is very severe respiratory failure; 80% of the patients&#xD;
      present with severe acute respiratory distress syndrome (SARS) that requires protective&#xD;
      mechanical ventilation.&#xD;
&#xD;
      Five percent of patients with SARS require extracorporeal circulation (ECMO) techniques.&#xD;
      Global mortality data has been thus far reported in different individual publications from&#xD;
      China. Without accounting for those patients still admitted to hospital, bona fide&#xD;
      information (from a hospital in Wuhan) received by the PI of this project estimates that&#xD;
      mortality of hospitalized patients is more than 10%. Evidently, mortality is concentrated in&#xD;
      patients admitted to the ICU and those patients who require mechanical ventilation and&#xD;
      present with SARS. As data in China was globally reported, risk factors and prognosis of&#xD;
      patients with and without SARS who require mechanical ventilation are not definitively known.&#xD;
      The efficacy of different treatments administered empirically or based on small, observation&#xD;
      studies is also not known. With many still admitted at the time of publication, a recent&#xD;
      study in JAMA about 1500 patients admitted to the ICU in the region of Lombardy (Italy)&#xD;
      reported a crude mortality rate of 25%. The data published until the current date is merely&#xD;
      observational, prospective or retrospective. Data has not been recorded by analysis performed&#xD;
      with artificial intelligence (machine learning) in order to report much more personalized&#xD;
      results. Furthermore, as it concerns patients admitted to the ICU who survive, respiratory&#xD;
      and cardiovascular consequences, as well as quality of living are completely unknown.&#xD;
&#xD;
      The study further aims to investigate quality of life and different respiratory and&#xD;
      cardiovascular outcomes at 6 months, as well as crude mortality within 1 year after discharge&#xD;
      of patients with COVID-19 who survive following ICU admission. Lastly, with the objective to&#xD;
      help personalize treatment in accordance with altered biological pathways in each patient,&#xD;
      two types of studies will be performed: 1) epigenetics and 2) predictive enrichment of&#xD;
      biomarkers in plasma.&#xD;
&#xD;
      Hypothesis&#xD;
&#xD;
        -  A significant percentage of patients (20%) admitted to the hospital with COVID-19&#xD;
           infection is expected to require ICU admission, and need mechanical ventilation (80%)&#xD;
           and, in a minor percentage (5%), ECMO.&#xD;
&#xD;
        -  Patients who survive an acute episode during ICU hospitalization will have a yearly&#xD;
           accumulated mortality of 40%. Those who then survive will have respiratory consequences,&#xD;
           cardiovascular complications and poor quality of life (6 months).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective and Purpose of Study&#xD;
&#xD;
        1. The main objective is to determine risks factors and prognosis of patients with COVID-19&#xD;
           infection who have been admitted to Spanish ICUs between the beginning and end of the&#xD;
           pandemic in Spain. Special attention will be placed on identifying differential&#xD;
           expression of prognostic factors based on sex.&#xD;
&#xD;
        2. The second objective is to perform a follow-up of patients within 6 months after&#xD;
           discharge from ICU and hospital in order to determine mortality (including at 1-year&#xD;
           mark), functional respiratory and cardiovascular consequences, and quality of life.&#xD;
&#xD;
        3. The third objective is to perform an epigenetic study in cases, in which a blood sample&#xD;
           can be drawn. The aim of such undertaking is to define molecular signatures in liquid&#xD;
           biopsies that can provide information regarding prognosis, and treatment monitoring and&#xD;
           response to therapy.&#xD;
&#xD;
        4. Lastly, predictive ability of response to therapy and mortality will be assessed from a&#xD;
           panel of protein biomarkers that participate in key physiological pathways of the&#xD;
           disease's pathogenesis. This could, in turn, help select prospective treatments with&#xD;
           greater potential of being successful in each patient.&#xD;
&#xD;
      Principal and Secondary Variables&#xD;
&#xD;
        1. Prior epidemiological data of the patient&#xD;
&#xD;
        2. Biological and clinical data, including treatment administered upon hospital admission&#xD;
&#xD;
        3. Biological and clinical data, including treatments administered upon and during ICU&#xD;
           admission until either discharge from ICU or hospital, or death&#xD;
&#xD;
        4. Specific data regarding artificial ventilation and ECMO since the beginning, as well as&#xD;
           sequentially, from intubation to either extubation or death&#xD;
&#xD;
        5. Biological and clinical data upon hospital discharge&#xD;
&#xD;
        6. Clinical follow-up of patients who survive within 6 months, including: functional&#xD;
           respiratory tests, echocardiograms and surveys regarding quality of life&#xD;
&#xD;
        7. Intrahospital and intra-ICU mortality will be registered at 28- and 90-day marks, as&#xD;
           well as within 6 months and 1 year&#xD;
&#xD;
        8. 1000 blood samples will be drawn for the epigenetic study The molecular profile of a&#xD;
           non-coding RNA (ncRNA), specifically the microRNA (miRNA) pattern in liquid biopsy, will&#xD;
           be analyzed. A circulating miRNA signature is closer to the phenotype than genomic&#xD;
           markers and can provide information regarding epigenetic regulation, cell activation,&#xD;
           tissue repair, and metabolic processes in addition to that afforded by clinical&#xD;
           predictors and classic risk factors. miRNAs offer appropriate biochemical properties&#xD;
           that are highly stable; have a long half-life in biological samples used in clinical&#xD;
           laboratories (serum/plasma); can be efficiently and relatively rapidly quantified with&#xD;
           high sensitivity and specificity by RT-qPCR; and can serve as a profitable tool for the&#xD;
           assessment of risks and disease control.&#xD;
&#xD;
      All of these characteristics have led distinct authors to propose the clinical application of&#xD;
      miRNA in either the short or medium term.&#xD;
&#xD;
      The experimental design comprises two phases. In the first approximation, a screening of&#xD;
      non-coding RNA (ncRNA) will be performed in a sub-population of patients (n=200). The number&#xD;
      of samples surpasses the quantity recommended for this type of studies. (Schurch y cols.,&#xD;
      RNA, 2016). A quotation will be requested for the screening of ncRNA by HTG EdgeSeq miRNA&#xD;
      Whole Transcriptome Assay system (HTG). Using next generation sequencing (NGS), this method&#xD;
      allows for the quantification of 2083 human candidates. All of the procedure steps will be&#xD;
      completed in suitable physical locations in accordance with code OP No. 0028. All of the&#xD;
      samples will be prepared in accordance with code No. 0036.&#xD;
&#xD;
      Screening results will be validated in the validation cohort (n=800) with RT-qPCR, a&#xD;
      gold-standard technique. The budget includes material necessary for RNA extraction (miRNeasy&#xD;
      Serum/Plasma isolation kits, Qiagen; spike-in; carrier RNA; consumables) and expression&#xD;
      quantification of ncRNA in biofluids (RT-qPCR miRCURY LNA Universal RT microRNA PCR System&#xD;
      kits, Qiagen; endogenous controls; consumables. Studies will be carried out at the TRRM Group&#xD;
      facilities in the IRBLleida. The laboratory has the necessary team and material to isolate&#xD;
      and quantify RNA, and store reagents and samples (cold stores, freezers of 20ºC and -80ºC).&#xD;
&#xD;
      9.- For the study of prognostic biomarkers, concentration of biomarkers in plasma that are&#xD;
      key to potentially useful drugs' mechanism of action in this disease will be assessed. This&#xD;
      quantification could provide guidance on drug usage (lymphocyte count will be obtained from a&#xD;
      blood count):&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 8, 2020</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">September 30, 2021</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>1 Year</target_duration>
  <primary_outcome>
    <measure>One year mortality</measure>
    <time_frame>At 12 months of ICU admission</time_frame>
    <description>People who died after one year of follow up</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Six month mortality</measure>
    <time_frame>At 6 month of ICU admission</time_frame>
    <description>People who died after one year of follow up</description>
  </primary_outcome>
  <enrollment type="Actual">8500</enrollment>
  <condition>Acute Respiratory Distress Syndrome</condition>
  <condition>Severe Pneumonia</condition>
  <condition>Respiratory Failure</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      For the epigenetic study, blood samples will be gathered from 1000 patients within 48 hours&#xD;
      after admission to the ICU. The collection and preparation of plasma samples will be done in&#xD;
      accordance with Early Detection Research Network (EDRN) Standard Operating Procedures&#xD;
      (National Cancer Institute, USA).&#xD;
&#xD;
      For the study of prognostic biomarkers, concentration of biomarkers in plasma that are key to&#xD;
      potentially useful drugs' mechanism of action in this disease will be assessed. Plasma&#xD;
      samples will be collected from 1000 patients within 48 hours after admission to the ICU.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients admitted to Spanish ICUs.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  1. Laboratory-confirmed COVID-19 infection with either real-time PCR or Next&#xD;
             Generation Sequencing (NGS)&#xD;
&#xD;
          -  2. Admission to intensive care unit&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Patients admitted to COVID-19-negative ICU&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Antoni Torres, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Spanish Research Center for Respiratory Diseases</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Universitario Central de Asturias</name>
      <address>
        <city>Oviedo</city>
        <state>Asturias</state>
        <zip>30011</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Bellvitge</name>
      <address>
        <city>Hospitalet de Llobregat</city>
        <state>Barcelona</state>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Mataró</name>
      <address>
        <city>Mataró</city>
        <state>Barcelona</state>
        <zip>08304</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General de Cataluña</name>
      <address>
        <city>Sant Cugat Del Vallès</city>
        <state>Barcelona</state>
        <zip>08195</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Infanta Margarita de Cabra</name>
      <address>
        <city>Cabra</city>
        <state>Córdoba</state>
        <zip>14940</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Lucus Augusti</name>
      <address>
        <city>Lugo</city>
        <state>Galicia</state>
        <zip>27003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Son Llatzer</name>
      <address>
        <city>Palma De Mallorca</city>
        <state>Mallorca</state>
        <zip>07198</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Álvaro Cunqueiro</name>
      <address>
        <city>Vigo</city>
        <state>Pontevedra</state>
        <zip>36213</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Verge de la Cinta</name>
      <address>
        <city>Tortosa</city>
        <state>Tarragona</state>
        <zip>43500</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Sant Joan d'Alacant</name>
      <address>
        <city>Alicante</city>
        <zip>03550</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clínica Sagrada Família</name>
      <address>
        <city>Barcelona</city>
        <zip>08022</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Sagrat Cor</name>
      <address>
        <city>Barcelona</city>
        <zip>08029</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vall d'Hebron University Hospital, Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Burgos</name>
      <address>
        <city>Burgos</city>
        <zip>09006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital San Pedro de Alcantara</name>
      <address>
        <city>Cáceres</city>
        <zip>10003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de León</name>
      <address>
        <city>León</city>
        <zip>24008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Arnau de Vilanova Lleida</name>
      <address>
        <city>Lleida</city>
        <zip>25198</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Infanta Leonor de Madrid</name>
      <address>
        <city>Madrid</city>
        <zip>28031</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complexo Hospitalario Universitario de Ourense</name>
      <address>
        <city>Ourense</city>
        <zip>32005</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Asistencial Universitario de Palencia</name>
      <address>
        <city>Palencia</city>
        <zip>34005</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Montecelo</name>
      <address>
        <city>Pontevedra</city>
        <zip>36071</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Salamanca</name>
      <address>
        <city>Salamanca</city>
        <zip>37007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Virgen de Valme</name>
      <address>
        <city>Sevilla</city>
        <zip>41014</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari de Tarragona Joan XXIII</name>
      <address>
        <city>Tarragona</city>
        <zip>43005</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínic Universitari de València</name>
      <address>
        <city>Valencia</city>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari i Politècnic La Fe</name>
      <address>
        <city>Valencia</city>
        <zip>46026</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Valladolid</name>
      <address>
        <city>Valladolid</city>
        <zip>47003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Nuestra Señora de Gracia</name>
      <address>
        <city>Zaragoza</city>
        <zip>50004</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>July 20, 2022</last_update_submitted>
  <last_update_submitted_qc>July 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 21, 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>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Respiratory Insufficiency</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All IPD anonymized that underlie results in a publication will be available after publication.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>After publication</ipd_time_frame>
    <ipd_access_criteria>Data will be available after reasoning requested.</ipd_access_criteria>
  </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/NCT04457505
org study id: CIBERESUCICOVID
nct id: NCT04457505
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The latest epidemiological data published from Chine reports that up to 30% of
      hospital-admitted patients required admission to intensive care units (ICU). The cause for
      ICU admission for most patients is very severe respiratory failure; 80% of the patients
      present with severe acute respiratory distress syndrome (SARS) that requires protective
      mechanical ventilation.

      Five percent of patients with SARS require extracorporeal circulation (ECMO) techniques.
      Global mortality data has been thus far reported in different individual publications from
      China. Without accounting for those patients still admitted to hospital, bona fide
      information (from a hospital in Wuhan) received by the PI of this project estimates that
      mortality of hospitalized patients is more than 10%. Evidently, mortality is concentrated in
      patients admitted to the ICU and those patients who require mechanical ventilation and
      present with SARS. As data in China was globally reported, risk factors and prognosis of
      patients with and without SARS who require mechanical ventilation are not definitively known.
      The efficacy of different treatments administered empirically or based on small, observation
      studies is also not known. With many still admitted at the time of publication, a recent
      study in JAMA about 1500 patients admitted to the ICU in the region of Lombardy (Italy)
      reported a crude mortality rate of 25%. The data published until the current date is merely
      observational, prospective or retrospective. Data has not been recorded by analysis performed
      with artificial intelligence (machine learning) in order to report much more personalized
      results. Furthermore, as it concerns patients admitted to the ICU who survive, respiratory
      and cardiovascular consequences, as well as quality of living are completely unknown.

      The study further aims to investigate quality of life and different respiratory and
      cardiovascular outcomes at 6 months, as well as crude mortality within 1 year after discharge
      of patients with COVID-19 who survive following ICU admission. Lastly, with the objective to
      help personalize treatment in accordance with altered biological pathways in each patient,
      two types of studies will be performed: 1) epigenetics and 2) predictive enrichment of
      biomarkers in plasma.

      Hypothesis

        -  A significant percentage of patients (20%) admitted to the hospital with COVID-19
           infection is expected to require ICU admission, and need mechanical ventilation (80%)
           and, in a minor percentage (5%), ECMO.

        -  Patients who survive an acute episode during ICU hospitalization will have a yearly
           accumulated mortality of 40%. Those who then survive will have respiratory consequences,
           cardiovascular complications and poor quality of life (6 months).
Objective and Purpose of Study

        1. The main objective is to determine risks factors and prognosis of patients with COVID-19
           infection who have been admitted to Spanish ICUs between the beginning and end of the
           pandemic in Spain. Special attention will be placed on identifying differential
           expression of prognostic factors based on sex.

        2. The second objective is to perform a follow-up of patients within 6 months after
           discharge from ICU and hospital in order to determine mortality (including at 1-year
           mark), functional respiratory and cardiovascular consequences, and quality of life.

        3. The third objective is to perform an epigenetic study in cases, in which a blood sample
           can be drawn. The aim of such undertaking is to define molecular signatures in liquid
           biopsies that can provide information regarding prognosis, and treatment monitoring and
           response to therapy.

        4. Lastly, predictive ability of response to therapy and mortality will be assessed from a
           panel of protein biomarkers that participate in key physiological pathways of the
           disease's pathogenesis. This could, in turn, help select prospective treatments with
           greater potential of being successful in each patient.

      Principal and Secondary Variables

        1. Prior epidemiological data of the patient

        2. Biological and clinical data, including treatment administered upon hospital admission

        3. Biological and clinical data, including treatments administered upon and during ICU
           admission until either discharge from ICU or hospital, or death

        4. Specific data regarding artificial ventilation and ECMO since the beginning, as well as
           sequentially, from intubation to either extubation or death

        5. Biological and clinical data upon hospital discharge

        6. Clinical follow-up of patients who survive within 6 months, including: functional
           respiratory tests, echocardiograms and surveys regarding quality of life

        7. Intrahospital and intra-ICU mortality will be registered at 28- and 90-day marks, as
           well as within 6 months and 1 year

        8. 1000 blood samples will be drawn for the epigenetic study The molecular profile of a
           non-coding RNA (ncRNA), specifically the microRNA (miRNA) pattern in liquid biopsy, will
           be analyzed. A circulating miRNA signature is closer to the phenotype than genomic
           markers and can provide information regarding epigenetic regulation, cell activation,
           tissue repair, and metabolic processes in addition to that afforded by clinical
           predictors and classic risk factors. miRNAs offer appropriate biochemical properties
           that are highly stable; have a long half-life in biological samples used in clinical
           laboratories (serum/plasma); can be efficiently and relatively rapidly quantified with
           high sensitivity and specificity by RT-qPCR; and can serve as a profitable tool for the
           assessment of risks and disease control.

      All of these characteristics have led distinct authors to propose the clinical application of
      miRNA in either the short or medium term.

      The experimental design comprises two phases. In the first approximation, a screening of
      non-coding RNA (ncRNA) will be performed in a sub-population of patients (n=200). The number
      of samples surpasses the quantity recommended for this type of studies. (Schurch y cols.,
      RNA, 2016). A quotation will be requested for the screening of ncRNA by HTG EdgeSeq miRNA
      Whole Transcriptome Assay system (HTG). Using next generation sequencing (NGS), this method
      allows for the quantification of 2083 human candidates. All of the procedure steps will be
      completed in suitable physical locations in accordance with code OP No. 0028. All of the
      samples will be prepared in accordance with code No. 0036.

      Screening results will be validated in the validation cohort (n=800) with RT-qPCR, a
      gold-standard technique. The budget includes material necessary for RNA extraction (miRNeasy
      Serum/Plasma isolation kits, Qiagen; spike-in; carrier RNA; consumables) and expression
      quantification of ncRNA in biofluids (RT-qPCR miRCURY LNA Universal RT microRNA PCR System
      kits, Qiagen; endogenous controls; consumables. Studies will be carried out at the TRRM Group
      facilities in the IRBLleida. The laboratory has the necessary team and material to isolate
      and quantify RNA, and store reagents and samples (cold stores, freezers of 20ºC and -80ºC).

      9.- For the study of prognostic biomarkers, concentration of biomarkers in plasma that are
      key to potentially useful drugs' mechanism of action in this disease will be assessed. This
      quantification could provide guidance on drug usage (lymphocyte count will be obtained from a
      blood count):
observational model: Cohort
time perspective: Prospective
measure: One year mortality
time frame: At 12 months of ICU admission
description: People who died after one year of follow up
measure: Six month mortality
time frame: At 6 month of ICU admission
description: People who died after one year of follow up
For the epigenetic study, blood samples will be gathered from 1000 patients within 48 hours
      after admission to the ICU. The collection and preparation of plasma samples will be done in
      accordance with Early Detection Research Network (EDRN) Standard Operating Procedures
      (National Cancer Institute, USA).

      For the study of prognostic biomarkers, concentration of biomarkers in plasma that are key to
      potentially useful drugs' mechanism of action in this disease will be assessed. Plasma
      samples will be collected from 1000 patients within 48 hours after admission to the ICU.
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Antoni Torres, PhD
role: Principal Investigator
affiliation: Spanish Research Center for Respiratory Diseases
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country: Spain
responsible party type: Sponsor
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Respiratory Insufficiency
mesh term: Acute Lung Injury
sharing ipd: Yes
ipd description: All IPD anonymized that underlie results in a publication will be available after publication.
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: After publication
ipd access criteria: Data will be available after reasoning requested.