<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/NCT04411459</url>
  </required_header>
  <id_info>
    <org_study_id>273/2020/OSS/AUSLBO</org_study_id>
    <nct_id>NCT04411459</nct_id>
  </id_info>
  <brief_title>Risk Factors for Prolonged Invasive Mechanical Ventilation in COVID-19 Acute Respiratory Distress Syndrome</brief_title>
  <official_title>Risk Factors for Prolonged Invasive Mechanical Ventilation in COVID-19 Acute Respiratory Distress Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Azienda Usl di Bologna</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Lorenzo Gamberini</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Azienda Usl di Bologna</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>
      This multicentric prospective clinical practice study aims at evaluating clinical factors&#xD;
      associated with a prolonged invasive mechanical ventilation and other outcomes such as&#xD;
      mortality and ICU length of stay in patients affected from COVID-19 related pneumonia and&#xD;
      ARDS.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background&#xD;
&#xD;
      On February 21th 2020, SARS-CoV-2 outbreak erupted in Italy and, in the immediately&#xD;
      subsequent period, all the Italian regional Health Systems had to face with an overwhelming&#xD;
      increase of COVID-19 admissions requiring isolation, oxygen, ventilation and ICU beds.&#xD;
&#xD;
      The COVID-19 related pneumonia presented as a particular entity in terms of clinical&#xD;
      management and different ICUs adopt different clinical strategies, sometimes this is due to&#xD;
      the local resources' availability. Mortality rate of the patients admitted to ICU is up to&#xD;
      26%.&#xD;
&#xD;
      To date, it is not clear which clinical, pharmacological and radiologic factors relate to a&#xD;
      prolonged duration of mechanical ventilation, mortality and ICU length of stay and it's&#xD;
      urgent to understand these aspects in order to develop optimal strategies to allow faster but&#xD;
      safe paths for these patients.&#xD;
&#xD;
      Hypothesis and significance&#xD;
&#xD;
      SARS-CoV-2 related pneumonia ICU management is still undefined, in fact this entity seems to&#xD;
      have clinical aspects rather different from other forms of interstitial pulmonary syndromes&#xD;
      evolving in diffuse alveolar damage and many aspects related to ventilation such pulmonary&#xD;
      compliance, driving pressure and response to pronation are very different from what&#xD;
      traditionally observed from other forms of ARDS, moreover an abnormal trend towards&#xD;
      hypercoagulability has been described in these patients.&#xD;
&#xD;
      Different treatments have been proposed and are under evaluation such as Tocilizumab,&#xD;
      corticosteroids, hydroxychloroquine, antivirals, anticoagulants and antiplatelet therapies.&#xD;
&#xD;
      These treatments, together with common ICU practice aspects such as early/late tracheostomy,&#xD;
      ventilatory parameters believed adequate in order to start a weaning procedure, fluidic&#xD;
      balance, choice of analgesia and sedation regimens, are not standardized in this particular&#xD;
      syndrome due to the lack of evidence available and there is need for information about which&#xD;
      factors correlate to a lower duration of mechanical ventilation and mortality.&#xD;
&#xD;
      Collected data:&#xD;
&#xD;
        -  Demographics and anamnesis: age, sex, weight, height, previous pathologies&#xD;
           (Hypertension, Chronic ischemic heart disease, Chronic kidney disease, COPD, Diabetes,&#xD;
           Chronic liver disease, active cancer, immunosuppressive therapy), smoker status, therapy&#xD;
           with ACE-inhibitors, statins and Angiotensin II Receptor Blockers.&#xD;
&#xD;
        -  Conditions at ICU admission: date of symptoms onset (fever and or cough), date of&#xD;
           hospital admission, date of ICU admission, SOFA and SAPS II score, high flow nasal&#xD;
           oxygen therapy before intubation, NIV/CPAP trial before intubation, duration of the&#xD;
           NIV/CPAP trial, PaO2/FiO2 value before intubation, initial tidal volume set, initial&#xD;
           PEEP set, Initial pplateau observed.&#xD;
&#xD;
        -  Ventilation during the first 5 days: lowest PaO2/FiO2 value, ventilatory strategy&#xD;
           (pressure control ventilation vs volume control ventilation and volumes), lowest static&#xD;
           respiratory system compliance, highest driving pressure, highest PEEP, highest arterial&#xD;
           pCO2 observed, number and duration of pronation cycles, response in terms of oxygenation&#xD;
           to the first pronation, need for decapneization, use of nitric oxide, tracheostomy date,&#xD;
           need for extracorporeal membrane oxygenation treatment.&#xD;
&#xD;
        -  Pharmacologic strategies during the first 5 days: sedative regimen and maximum doses,&#xD;
           neuromuscular blocking agents (type of NMBA and duration of continuous infusion).&#xD;
&#xD;
        -  COVID specific therapies: antivirals (type, start and end date), chloroquine,&#xD;
           tocilizumab (start date and route of administration), intravenous corticosteroids, other&#xD;
           specific therapies.&#xD;
&#xD;
        -  Other supportive therapies: first line antibacterial regimen, amines (maximum dose),&#xD;
           renal replacement therapy, fluidic balance during the first 3 days after ICU admission,&#xD;
           anticoagulation, antiaggregation.&#xD;
&#xD;
        -  Complications during ICU stay:&#xD;
&#xD;
             -  Cardiovascular (myocardial infarction, new onset supraventricular or ventricular&#xD;
                arrhythmia, pulmonary embolism, pulmonary edema, haemorragic shock, cardiogenic&#xD;
                shock, acute peripheral ischemia, pneumothorax)&#xD;
&#xD;
             -  Neurologic (new onset ischemic stroke or cerebral haemorrage, critical illness&#xD;
                polyneuropathy / myopathy, new onset seizures)&#xD;
&#xD;
             -  Gastroenteric (gastrointestinal bleeding, severe diarrhea, intestinal occlusion,&#xD;
                gastrointestinal perforation/ischemia)&#xD;
&#xD;
             -  Extrapulmonary infections (documented blood steam, urinary tract, central nervous&#xD;
                system, abdominal infection)&#xD;
&#xD;
             -  Pulmonary infections after intubation (early onset VAP - &lt; 7 days of mechanical&#xD;
                ventilation, late onset VAP - ≥ 7 days of mechanical ventilation)&#xD;
&#xD;
        -  Weaning from mechanical ventilation: last day of highest PEEP, first attempt of pressure&#xD;
           support ventilation (PSV), P/F at the first attempt of PSV, entity of pressure support&#xD;
           at the first attempt of PSV, PEEP at the first attempt of PSV, day of extubation,&#xD;
           non-invasive ventilation or high flow oxygen therapy after extubation, first day of&#xD;
           spontaneous breathing, need for reintubation and date&#xD;
&#xD;
        -  Radiology: first available CT, last CT before ICU admission and intubation, last ICU&#xD;
           follow-up CT. First available chest X ray, last chest X ray before ICU admission and&#xD;
           intubation, last ICU- follow up chest X ray. 30 days follow-up CT (if available).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2020</start_date>
  <completion_date type="Actual">October 16, 2020</completion_date>
  <primary_completion_date type="Actual">June 30, 2020</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>Duration of mechanical ventilation and 28 days ventilator free days</measure>
    <time_frame>28 days</time_frame>
    <description>Ventilator free days (VFDs) will be calculated in a time frame of 28 days, the beginning of observation will coincide with the day of intubation and observation will end after successful disconnection from mechanical ventilation.&#xD;
For intubated patients, post extubation non invasive ventilation (NIV) will not be accounted as a ventilation period, in case of interval reintubation within 28 days, VFDs will be counted from the last successful extubation.&#xD;
For tracheostomized patients, ventilator free days will be counted after successful disconnection from mechanical ventilation and interval reconnections will be considered in the ventilation interval as for intubated patients.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ICU Mortality</measure>
    <time_frame>60 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>30 days survival after ICU discharge</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>90 days survival after ICU discharge</measure>
    <time_frame>90 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life at 90 days after ICU discharge measured with 15D instrument</measure>
    <time_frame>90 days</time_frame>
    <description>15D instrument (http://www.15d-instrument.net/15d/) will be administered via telephonic interview&#xD;
Areas assessed: MOBILITY, VISION, HEARING, BREATHING, SLEEPING, EATING, SPEECH, EXCRETION, USUAL ACTIVITIES, MENTAL FUNCTION, DISCOMFORT AND SYMPTOMS, DEPRESSION, DISTRESS, VITALITY, SEXUAL ACTIVITY</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiologic aspects - structured description of CT and RX data</measure>
    <time_frame>90 days</time_frame>
    <description>First available CT, last CT before ICU admission and intubation, last ICU follow-up CT. First available chest X ray, last chest X ray before ICU admission and intubation, last ICU- follow up chest X ray and 30 days follow-up CT (if available) will be evaluated, if available.&#xD;
Structured description&#xD;
CT scan&#xD;
Date: yyyy/mm/dd Parenchymal alterations: ground glass, crazy paving, parenchymal consolidation Extension: monolateral, bilateral Number of lobes involved: (1-5) Percentage of parenchymal involvement: 0-100% Distribution: subpleural, random, diffuse&#xD;
X-ray scan&#xD;
Date: yyyy/mm/dd Main aspects: normal, focal lesions, monolateral multifocal lesions (right/left), diffuse multifocal lesions Lesion aspects: interstitial, interstitial/alveolar, alveolar, consolidations Pleural effusion presence and entity&#xD;
Pulmonary involvement score:&#xD;
0 = no involvement&#xD;
=&lt; 25%&#xD;
= 25-50% 3= 50-75%&#xD;
4 =&gt; 75% Total score (0-6): score of the right lung + score of the left lung</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life at 1 year after ICU discharge and persistent symptoms</measure>
    <time_frame>1 year</time_frame>
    <description>15D instrument (http://www.15d-instrument.net/15d/) will be administered via telephonic interview&#xD;
Areas assessed: MOBILITY, VISION, HEARING, BREATHING, SLEEPING, EATING, SPEECH, EXCRETION, USUAL ACTIVITIES, MENTAL FUNCTION, DISCOMFORT AND SYMPTOMS, DEPRESSION, DISTRESS, VITALITY, SEXUAL ACTIVITY&#xD;
Persistent symptoms explored: Dyspnea measured with mMRC scale, palpitations, cough, arthromyalgia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiologic aspects at 1 year CT scan</measure>
    <time_frame>1 year</time_frame>
    <description>Presence and extension of pulmonary fibrosing and non fibrosing signs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary function tests at 1 year - FEV1%</measure>
    <time_frame>1 year</time_frame>
    <description>FEV1% - Forced expiratory volume 1 second, % of predicted value referred to normative population</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary function tests at 1 year - FVC%</measure>
    <time_frame>1 year</time_frame>
    <description>FVC% - Forced vital capacity, % of predicted value referred to normative population</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary function tests at 1 year - FEV1/FVC%</measure>
    <time_frame>1 year</time_frame>
    <description>FEV1/FVC% - Forced expiratory volume 1 second/Forced Vital capacity, % of predicted value referred to normative population</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary function tests at 1 year -</measure>
    <time_frame>1 year</time_frame>
    <description>DLCO% - Diffusing capacity for carbon monoxide, % of predicted value referred to normative population</description>
  </secondary_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">470</enrollment>
  <condition>COVID-19</condition>
  <condition>Mechanical Ventilation</condition>
  <condition>Quality of Life</condition>
  <condition>Radiologic Increased Density of Lung</condition>
  <condition>Sedation</condition>
  <condition>Complication of Treatment</condition>
  <arm_group>
    <arm_group_label>COVID-19 pneumonia patients</arm_group_label>
    <description>Patients needing intubation and mechanical ventilation for COVID-19 related pneumonia without other primary causes of ICU admission</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Invasive mechanical ventilation</intervention_name>
    <description>Invasive mechanical ventilation for respiratory failure associated to COVID-19 pneumonia</description>
    <arm_group_label>COVID-19 pneumonia patients</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        This study enrolls patients admitted to ICU needing intubation and mechanical ventilation&#xD;
        bacause of respiratory failure for COVID-19 pneumonia without other primary causes for ICU&#xD;
        admission&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  ICU admission because of the need of mechanical ventilation in the context of COVID-19&#xD;
             related pneumonia (swab proven)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  COVID-19 related pneumonia complicating the clinical course of patients admitted to&#xD;
             the ICU for another reason (e.g. trauma, stroke)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Ospedale Santa Maria Annunziata - Anestesia e Rianimazione</name>
      <address>
        <city>Bagno A Ripoli</city>
        <state>FI</state>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. SS. Antonio, Biagio e Cesare Arrigo - Anestesia e Rianimazione</name>
      <address>
        <city>Alessandria</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anestesia e Rianimazione - Ospedale Civile di Baggiovara</name>
      <address>
        <city>Baggiovara</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anestesia e Rianimazione - Ospedale di Bentivoglio</name>
      <address>
        <city>Bentivoglio</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Unità Sanitaria Locale</name>
      <address>
        <city>Bologna</city>
        <zip>40100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anestesia e Rianimazione - Ospedale Bellaria</name>
      <address>
        <city>Bologna</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anestesia e Rianimazione - Policlinico Universitario S.Orsola - Malpighi</name>
      <address>
        <city>Bologna</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anestesia e Terapia intensiva dei trapianti addominali e chirurgia epatobiliare - Policlinico Universitario S.Orsola - Malpighi</name>
      <address>
        <city>Bologna</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anestesia e Terapia Intensiva Polivalente - Policlinico Universitario S.Orsola - Malpighi</name>
      <address>
        <city>Bologna</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale SS. Trinità - Anestesia e Rianimazione</name>
      <address>
        <city>Borgomanero</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anestesia e Rianimazione - Ospedale M. Bufalini</name>
      <address>
        <city>Cesena</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anestesia e Rianimazione - Ospedale degli Infermi</name>
      <address>
        <city>Faenza</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anestesia e Rianimazione Universitaria - Arcispedale Sant'Anna Ferrara</name>
      <address>
        <city>Ferrara</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anestesia e Rianimazione - Ospedale Morgagni - Pierantoni</name>
      <address>
        <city>Forlì</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anestesia e Rianimazione - Ospedale di Imola S.Maria della Scaletta</name>
      <address>
        <city>Imola</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Santo Stefano - Anestesia e Rianimazione</name>
      <address>
        <city>Prato</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anestesia e Rianimazione - Ospedale S. Maria delle Croci</name>
      <address>
        <city>Ravenna</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anestesia e Rianimazione - Arcispedale Santa Maria Nuova</name>
      <address>
        <city>Reggio Emilia</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anestesia e Rianimazione - Ospedale di Riccione</name>
      <address>
        <city>Riccione</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anestesia e Rianimazione - Ospedale Infermi</name>
      <address>
        <city>Rimini</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Yehya N, Harhay MO, Curley MAQ, Schoenfeld DA, Reeder RW. Reappraisal of Ventilator-Free Days in Critical Care Research. Am J Respir Crit Care Med. 2019 Oct 1;200(7):828-836. doi: 10.1164/rccm.201810-2050CP.</citation>
    <PMID>31034248</PMID>
  </reference>
  <reference>
    <citation>Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, Camporota L. COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med. 2020 Jun;46(6):1099-1102. doi: 10.1007/s00134-020-06033-2. Epub 2020 Apr 14. No abstract available.</citation>
    <PMID>32291463</PMID>
  </reference>
  <results_reference>
    <citation>Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L, Castelli A, Cereda D, Coluccello A, Foti G, Fumagalli R, Iotti G, Latronico N, Lorini L, Merler S, Natalini G, Piatti A, Ranieri MV, Scandroglio AM, Storti E, Cecconi M, Pesenti A; COVID-19 Lombardy ICU Network. Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020 Apr 28;323(16):1574-1581. doi: 10.1001/jama.2020.5394. Erratum In: JAMA. 2021 May 25;325(20):2120.</citation>
    <PMID>32250385</PMID>
  </results_reference>
  <results_reference>
    <citation>Bhatraju PK, Ghassemieh BJ, Nichols M, Kim R, Jerome KR, Nalla AK, Greninger AL, Pipavath S, Wurfel MM, Evans L, Kritek PA, West TE, Luks A, Gerbino A, Dale CR, Goldman JD, O'Mahony S, Mikacenic C. Covid-19 in Critically Ill Patients in the Seattle Region - Case Series. N Engl J Med. 2020 May 21;382(21):2012-2022. doi: 10.1056/NEJMoa2004500. Epub 2020 Mar 30.</citation>
    <PMID>32227758</PMID>
  </results_reference>
  <results_reference>
    <citation>Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW; the Northwell COVID-19 Research Consortium; Barnaby DP, Becker LB, Chelico JD, Cohen SL, Cookingham J, Coppa K, Diefenbach MA, Dominello AJ, Duer-Hefele J, Falzon L, Gitlin J, Hajizadeh N, Harvin TG, Hirschwerk DA, Kim EJ, Kozel ZM, Marrast LM, Mogavero JN, Osorio GA, Qiu M, Zanos TP. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 May 26;323(20):2052-2059. doi: 10.1001/jama.2020.6775. Erratum In: JAMA. 2020 May 26;323(20):2098.</citation>
    <PMID>32320003</PMID>
  </results_reference>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>May 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>August 27, 2021</last_update_submitted>
  <last_update_submitted_qc>August 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>Mechanical Ventilation</keyword>
  <keyword>Quality of life</keyword>
  <keyword>Complications during ICU stay</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
  </condition_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/NCT04411459
org study id: 273/2020/OSS/AUSLBO
nct id: NCT04411459
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This multicentric prospective clinical practice study aims at evaluating clinical factors
      associated with a prolonged invasive mechanical ventilation and other outcomes such as
      mortality and ICU length of stay in patients affected from COVID-19 related pneumonia and
      ARDS.
Background

      On February 21th 2020, SARS-CoV-2 outbreak erupted in Italy and, in the immediately
      subsequent period, all the Italian regional Health Systems had to face with an overwhelming
      increase of COVID-19 admissions requiring isolation, oxygen, ventilation and ICU beds.

      The COVID-19 related pneumonia presented as a particular entity in terms of clinical
      management and different ICUs adopt different clinical strategies, sometimes this is due to
      the local resources' availability. Mortality rate of the patients admitted to ICU is up to
      26%.

      To date, it is not clear which clinical, pharmacological and radiologic factors relate to a
      prolonged duration of mechanical ventilation, mortality and ICU length of stay and it's
      urgent to understand these aspects in order to develop optimal strategies to allow faster but
      safe paths for these patients.

      Hypothesis and significance

      SARS-CoV-2 related pneumonia ICU management is still undefined, in fact this entity seems to
      have clinical aspects rather different from other forms of interstitial pulmonary syndromes
      evolving in diffuse alveolar damage and many aspects related to ventilation such pulmonary
      compliance, driving pressure and response to pronation are very different from what
      traditionally observed from other forms of ARDS, moreover an abnormal trend towards
      hypercoagulability has been described in these patients.

      Different treatments have been proposed and are under evaluation such as Tocilizumab,
      corticosteroids, hydroxychloroquine, antivirals, anticoagulants and antiplatelet therapies.

      These treatments, together with common ICU practice aspects such as early/late tracheostomy,
      ventilatory parameters believed adequate in order to start a weaning procedure, fluidic
      balance, choice of analgesia and sedation regimens, are not standardized in this particular
      syndrome due to the lack of evidence available and there is need for information about which
      factors correlate to a lower duration of mechanical ventilation and mortality.

      Collected data:

        -  Demographics and anamnesis: age, sex, weight, height, previous pathologies
           (Hypertension, Chronic ischemic heart disease, Chronic kidney disease, COPD, Diabetes,
           Chronic liver disease, active cancer, immunosuppressive therapy), smoker status, therapy
           with ACE-inhibitors, statins and Angiotensin II Receptor Blockers.

        -  Conditions at ICU admission: date of symptoms onset (fever and or cough), date of
           hospital admission, date of ICU admission, SOFA and SAPS II score, high flow nasal
           oxygen therapy before intubation, NIV/CPAP trial before intubation, duration of the
           NIV/CPAP trial, PaO2/FiO2 value before intubation, initial tidal volume set, initial
           PEEP set, Initial pplateau observed.

        -  Ventilation during the first 5 days: lowest PaO2/FiO2 value, ventilatory strategy
           (pressure control ventilation vs volume control ventilation and volumes), lowest static
           respiratory system compliance, highest driving pressure, highest PEEP, highest arterial
           pCO2 observed, number and duration of pronation cycles, response in terms of oxygenation
           to the first pronation, need for decapneization, use of nitric oxide, tracheostomy date,
           need for extracorporeal membrane oxygenation treatment.

        -  Pharmacologic strategies during the first 5 days: sedative regimen and maximum doses,
           neuromuscular blocking agents (type of NMBA and duration of continuous infusion).

        -  COVID specific therapies: antivirals (type, start and end date), chloroquine,
           tocilizumab (start date and route of administration), intravenous corticosteroids, other
           specific therapies.

        -  Other supportive therapies: first line antibacterial regimen, amines (maximum dose),
           renal replacement therapy, fluidic balance during the first 3 days after ICU admission,
           anticoagulation, antiaggregation.

        -  Complications during ICU stay:

             -  Cardiovascular (myocardial infarction, new onset supraventricular or ventricular
                arrhythmia, pulmonary embolism, pulmonary edema, haemorragic shock, cardiogenic
                shock, acute peripheral ischemia, pneumothorax)

             -  Neurologic (new onset ischemic stroke or cerebral haemorrage, critical illness
                polyneuropathy / myopathy, new onset seizures)

             -  Gastroenteric (gastrointestinal bleeding, severe diarrhea, intestinal occlusion,
                gastrointestinal perforation/ischemia)

             -  Extrapulmonary infections (documented blood steam, urinary tract, central nervous
                system, abdominal infection)

             -  Pulmonary infections after intubation (early onset VAP - < 7 days of mechanical
                ventilation, late onset VAP - ≥ 7 days of mechanical ventilation)

        -  Weaning from mechanical ventilation: last day of highest PEEP, first attempt of pressure
           support ventilation (PSV), P/F at the first attempt of PSV, entity of pressure support
           at the first attempt of PSV, PEEP at the first attempt of PSV, day of extubation,
           non-invasive ventilation or high flow oxygen therapy after extubation, first day of
           spontaneous breathing, need for reintubation and date

        -  Radiology: first available CT, last CT before ICU admission and intubation, last ICU
           follow-up CT. First available chest X ray, last chest X ray before ICU admission and
           intubation, last ICU- follow up chest X ray. 30 days follow-up CT (if available).
observational model: Cohort
time perspective: Prospective
measure: Duration of mechanical ventilation and 28 days ventilator free days
time frame: 28 days
description: Ventilator free days (VFDs) will be calculated in a time frame of 28 days, the beginning of observation will coincide with the day of intubation and observation will end after successful disconnection from mechanical ventilation.
For intubated patients, post extubation non invasive ventilation (NIV) will not be accounted as a ventilation period, in case of interval reintubation within 28 days, VFDs will be counted from the last successful extubation.
For tracheostomized patients, ventilator free days will be counted after successful disconnection from mechanical ventilation and interval reconnections will be considered in the ventilation interval as for intubated patients.
measure: ICU Mortality
time frame: 60 days
measure: 30 days survival after ICU discharge
time frame: 30 days
measure: 90 days survival after ICU discharge
time frame: 90 days
measure: Quality of life at 90 days after ICU discharge measured with 15D instrument
time frame: 90 days
description: 15D instrument (http://www.15d-instrument.net/15d/) will be administered via telephonic interview
Areas assessed: MOBILITY, VISION, HEARING, BREATHING, SLEEPING, EATING, SPEECH, EXCRETION, USUAL ACTIVITIES, MENTAL FUNCTION, DISCOMFORT AND SYMPTOMS, DEPRESSION, DISTRESS, VITALITY, SEXUAL ACTIVITY
measure: Radiologic aspects - structured description of CT and RX data
time frame: 90 days
description: First available CT, last CT before ICU admission and intubation, last ICU follow-up CT. First available chest X ray, last chest X ray before ICU admission and intubation, last ICU- follow up chest X ray and 30 days follow-up CT (if available) will be evaluated, if available.
Structured description
CT scan
Date: yyyy/mm/dd Parenchymal alterations: ground glass, crazy paving, parenchymal consolidation Extension: monolateral, bilateral Number of lobes involved: (1-5) Percentage of parenchymal involvement: 0-100% Distribution: subpleural, random, diffuse
X-ray scan
Date: yyyy/mm/dd Main aspects: normal, focal lesions, monolateral multifocal lesions (right/left), diffuse multifocal lesions Lesion aspects: interstitial, interstitial/alveolar, alveolar, consolidations Pleural effusion presence and entity
Pulmonary involvement score:
0 = no involvement
=< 25%
= 25-50% 3= 50-75%
4 => 75% Total score (0-6): score of the right lung + score of the left lung
measure: Quality of life at 1 year after ICU discharge and persistent symptoms
time frame: 1 year
description: 15D instrument (http://www.15d-instrument.net/15d/) will be administered via telephonic interview
Areas assessed: MOBILITY, VISION, HEARING, BREATHING, SLEEPING, EATING, SPEECH, EXCRETION, USUAL ACTIVITIES, MENTAL FUNCTION, DISCOMFORT AND SYMPTOMS, DEPRESSION, DISTRESS, VITALITY, SEXUAL ACTIVITY
Persistent symptoms explored: Dyspnea measured with mMRC scale, palpitations, cough, arthromyalgia
measure: Radiologic aspects at 1 year CT scan
time frame: 1 year
description: Presence and extension of pulmonary fibrosing and non fibrosing signs
measure: Pulmonary function tests at 1 year - FEV1%
time frame: 1 year
description: FEV1% - Forced expiratory volume 1 second, % of predicted value referred to normative population
measure: Pulmonary function tests at 1 year - FVC%
time frame: 1 year
description: FVC% - Forced vital capacity, % of predicted value referred to normative population
measure: Pulmonary function tests at 1 year - FEV1/FVC%
time frame: 1 year
description: FEV1/FVC% - Forced expiratory volume 1 second/Forced Vital capacity, % of predicted value referred to normative population
measure: Pulmonary function tests at 1 year -
time frame: 1 year
description: DLCO% - Diffusing capacity for carbon monoxide, % of predicted value referred to normative population
arm group label: COVID-19 pneumonia patients
description: Patients needing intubation and mechanical ventilation for COVID-19 related pneumonia without other primary causes of ICU admission
intervention type: Other
intervention name: Invasive mechanical ventilation
description: Invasive mechanical ventilation for respiratory failure associated to COVID-19 pneumonia
arm group label: COVID-19 pneumonia patients
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: Italy
citation: Yehya N, Harhay MO, Curley MAQ, Schoenfeld DA, Reeder RW. Reappraisal of Ventilator-Free Days in Critical Care Research. Am J Respir Crit Care Med. 2019 Oct 1;200(7):828-836. doi: 10.1164/rccm.201810-2050CP.
PMID: 31034248
citation: Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, Camporota L. COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med. 2020 Jun;46(6):1099-1102. doi: 10.1007/s00134-020-06033-2. Epub 2020 Apr 14. No abstract available.
PMID: 32291463
citation: Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L, Castelli A, Cereda D, Coluccello A, Foti G, Fumagalli R, Iotti G, Latronico N, Lorini L, Merler S, Natalini G, Piatti A, Ranieri MV, Scandroglio AM, Storti E, Cecconi M, Pesenti A; COVID-19 Lombardy ICU Network. Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020 Apr 28;323(16):1574-1581. doi: 10.1001/jama.2020.5394. Erratum In: JAMA. 2021 May 25;325(20):2120.
PMID: 32250385
citation: Bhatraju PK, Ghassemieh BJ, Nichols M, Kim R, Jerome KR, Nalla AK, Greninger AL, Pipavath S, Wurfel MM, Evans L, Kritek PA, West TE, Luks A, Gerbino A, Dale CR, Goldman JD, O'Mahony S, Mikacenic C. Covid-19 in Critically Ill Patients in the Seattle Region - Case Series. N Engl J Med. 2020 May 21;382(21):2012-2022. doi: 10.1056/NEJMoa2004500. Epub 2020 Mar 30.
PMID: 32227758
citation: Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW; the Northwell COVID-19 Research Consortium; Barnaby DP, Becker LB, Chelico JD, Cohen SL, Cookingham J, Coppa K, Diefenbach MA, Dominello AJ, Duer-Hefele J, Falzon L, Gitlin J, Hajizadeh N, Harvin TG, Hirschwerk DA, Kim EJ, Kozel ZM, Marrast LM, Mogavero JN, Osorio GA, Qiu M, Zanos TP. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 May 26;323(20):2052-2059. doi: 10.1001/jama.2020.6775. Erratum In: JAMA. 2020 May 26;323(20):2098.
PMID: 32320003
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury
sharing ipd: No