xml: <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/NCT06002841</url>
    </required_header>
    <id_info>
      <org_study_id>EVs_2023</org_study_id>
      <nct_id>NCT06002841</nct_id>
    </id_info>
    <brief_title>Extracellular Vesicles From Mesenchymal Cells in the Treatment of Acute Respiratory Failure</brief_title>
    <official_title>Extracellular Vesicles From Mesenchymal Cells in the Treatment of Acute Respiratory Failure Associated With SARS-CoV-2 and Other Etiologies: a Clinical Trial, Randomized, Double-blind.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>D'Or Institute for Research and Education</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Hospital Sao Rafael</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Rio de Janeiro State Research Supporting Foundation (FAPERJ)</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Oswaldo Cruz Foundation</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>D'Or Institute for Research and Education</source>
    <oversight_info>
      <has_dmc>Yes</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 is a phase I/II, randomized, double-blind, placebo-controlled clinical trial that will&#xD;
        evaluate the safety and potential efficacy of therapy with extracellular vesicles (EVs)&#xD;
        obtained from mesenchymal stromal cells (MSCs), patients with moderate to severe acute&#xD;
        respiratory distress syndrome due to COVID-19 or other etiology. Participants will be&#xD;
        allocated to receive EVs obtained from MSCs or placebo (equal volume of Plasma-Lyte A).&#xD;
        Blinding will cover the participants, the multidisciplinary intensive care team and the&#xD;
        investigators.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The studied population will consist of 15 patients diagnosed with acute respiratory failure&#xD;
        syndrome admitted to the intensive care unit of Hospital São Rafael. This research aims to&#xD;
        assess the safety and potential effectiveness of intravenous therapy using extracellular&#xD;
        vesicles derived from mesenchymal cells in patients with moderate to severe acute respiratory&#xD;
        distress syndrome. The treatment group will receive intravenous administration of&#xD;
        extracellular vesicles obtained from mesenchymal cells, while the control group will receive&#xD;
        a placebo.&#xD;
  &#xD;
        EV group: will consist of 10 participants who will receive two infusions of 25 mL of the&#xD;
        investigational product (Plasma-Lyte A solution containing EVs obtained from MSCs),&#xD;
        intravenously, at intervals of 48 h.&#xD;
  &#xD;
        Placebo group: will consist of 5 participants who will receive an equal volume of Plasma-Lyte&#xD;
        A, intravenously, following the same schedule as the IV group: two infusions with an interval&#xD;
        of 48 hours.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">February 1, 2024</start_date>
    <completion_date type="Anticipated">June 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">June 1, 2025</primary_completion_date>
    <phase>Phase 1/Phase 2</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>
      <intervention_model_description>Parallel Assignment</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
      <masking_description>The treatment and placebo solutions will be indistinguishable in terms of their appearance. Stringent protocols will be established to guarantee that the physicians responsible for assessing patient safety, evaluating efficacy outcomes, and conducting laboratory analyses will be blinded to the randomization codes.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Measure administration of extracellular vesicles (EVs) up to 28 days</measure>
      <time_frame>28 days</time_frame>
      <description>Measure as reported adverse events up to 28 days after treatment or placebo administration to evaluate safety of treatment</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>All-cause mortality</measure>
      <time_frame>Day 14 and day 28</time_frame>
      <description>at days 14 and 28 after randomization;</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Variation in the Ratio PaO2/FiO2</measure>
      <time_frame>Baseline, day 01, day 02 and day 07</time_frame>
      <description>PaO2 (arterial partial pressure of oxygen)/FiO2 (fraction of inspired oxygen) on the day of randomization and at 24 hours, 48 hours and 7 days after the first infusion;</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Variation in the SOFA index</measure>
      <time_frame>day 01, day 02, day 07, day 09, day 14 and day 29</time_frame>
      <description>Variation in the SOFA index (Assessment of Sequential Organ Failure) at the time of randomization and during follow-up until discharge from the intensive care unit;</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Exploratory laboratory analysis</measure>
      <time_frame>30 days</time_frame>
      <description>variation in total and differential laboratory analysis.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of the period of hospitalization</measure>
      <time_frame>30 days</time_frame>
      <description>from hospital time in the intensive care unit (ICU)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of the period of ICU ventilation</measure>
      <time_frame>30 days</time_frame>
      <description>If applicable,will be measured the time of mechanical ventilation.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">15</enrollment>
    <condition>Severe Acute Respiratory Syndrome (SARS)</condition>
    <condition>Acute Respiratory Distress Syndrome (ARDS)</condition>
    <condition>Pneumonia</condition>
    <arm_group>
      <arm_group_label>EV group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>will consist of 10 participants who will receive two infusions of 25 mL of the investigational product (Plasma-Lyte A solution containing EVs obtained from MSCs), intravenously, at intervals of 48 h.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo group</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>will consist of 5 participants who will receive an equal volume of Plasma-Lyte A, intravenously, following the same schedule as the IV group: two infusions with an interval of 48 hours.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>intravenous treatment with EVs</intervention_name>
      <description>intravenous treatment with extracellular vesicles</description>
      <arm_group_label>EV group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>intravenous treatment with placebo solution</intervention_name>
      <description>intravenous treatment with placebo solution (without extracellular vesicles)</description>
      <arm_group_label>Placebo group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age &gt;= 18 years old;&#xD;
  &#xD;
            -  Chest CT radiological image with ground-glass opacities or chest X-ray with -&#xD;
               bilateral infiltrates characteristic of pulmonary edema;&#xD;
  &#xD;
            -  In invasive mechanical ventilation with PEEP 5 cm H2O and PaO2/FiO2&lt;250mmHg;&#xD;
  &#xD;
            -  Respiratory failure not explained by cardiac causes or fluid overload.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Unable to provide informed consent;&#xD;
  &#xD;
            -  Pregnancy or breastfeeding;&#xD;
  &#xD;
            -  Patients with active malignancy who have received chemotherapy in the last 2 years;&#xD;
  &#xD;
            -  Life expectancy of less than 6 months or in exclusive palliative care;&#xD;
  &#xD;
            -  Severe liver failure, with a Child-Pugh score &gt; 12;&#xD;
  &#xD;
            -  Previous renal failure: patients already undergoing dialysis or patients with GFR &lt;&#xD;
               30ml/min/1.73 m2&#xD;
  &#xD;
            -  Clinical or radiological suspicion of tuberculosis;&#xD;
  &#xD;
            -  Chronic respiratory failure;&#xD;
  &#xD;
            -  Use of ECMO;&#xD;
  &#xD;
            -  Moribund (high probability of death within the next 48 hours).&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Bruno Souza, M.D</last_name>
      <role>Principal Investigator</role>
      <affiliation>Instituto D'Or de Pesquisa e Ensino (IDOR), Salvador, Brazil</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Patrícia Rocco, M.D</last_name>
      <role>Principal Investigator</role>
      <affiliation>Universidade Federal do Rio de Janeiro (UFRJ)</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Carolina Nonaka, phD</last_name>
      <phone>+55 (71) 3281-6970</phone>
      <email>carolina.nonaka@hsr.com.br</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Ingrid Barbosa, B.Sc</last_name>
      <phone>+551121098855</phone>
      <email>nape@idor.org</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Hospital São Rafael</name>
        <address>
          <city>Salvador</city>
          <state>Bahia</state>
          <zip>41253-190</zip>
          <country>Brazil</country>
        </address>
      </facility>
      <contact>
        <last_name>Carolina Nonaka, phD</last_name>
        <phone>+55 (71) 3281-6970</phone>
        <email>carolina.nonaka@hsr.com.br</email>
      </contact>
      <contact_backup>
        <last_name>Tânia Aravena, B.Sc</last_name>
        <phone>+55 (71) 98748-6532</phone>
        <email>tania.mariela@hsr.com.br</email>
      </contact_backup>
      <investigator>
        <last_name>Bruno Souza, M.D</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Patricia Rocco, M.D</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Brazil</country>
    </location_countries>
    <reference>
      <citation>Abels ER, Breakefield XO. Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake. Cell Mol Neurobiol. 2016 Apr;36(3):301-12. doi: 10.1007/s10571-016-0366-z. Epub 2016 Apr 6.</citation>
      <PMID>27053351</PMID>
    </reference>
    <reference>
      <citation>Alipoor SD, Mortaz E, Garssen J, Movassaghi M, Mirsaeidi M, Adcock IM. Exosomes and Exosomal miRNA in Respiratory Diseases. Mediators Inflamm. 2016;2016:5628404. doi: 10.1155/2016/5628404. Epub 2016 Sep 25.</citation>
      <PMID>27738390</PMID>
    </reference>
    <reference>
      <citation>Antunes MA, Braga CL, Oliveira TB, Kitoko JZ, Castro LL, Xisto DG, Coelho MS, Rocha N, Silva-Aguiar RP, Caruso-Neves C, Martins EG, Carvalho CF, Galina A, Weiss DJ, Lapa E Silva JR, Lopes-Pacheco M, Cruz FF, Rocco PRM. Mesenchymal Stromal Cells From Emphysematous Donors and Their Extracellular Vesicles Are Unable to Reverse Cardiorespiratory Dysfunction in Experimental Severe Emphysema. Front Cell Dev Biol. 2021 May 31;9:661385. doi: 10.3389/fcell.2021.661385. eCollection 2021.</citation>
      <PMID>34136481</PMID>
    </reference>
    <reference>
      <citation>de Castro LL, Xisto DG, Kitoko JZ, Cruz FF, Olsen PC, Redondo PAG, Ferreira TPT, Weiss DJ, Martins MA, Morales MM, Rocco PRM. Human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthma. Stem Cell Res Ther. 2017 Jun 24;8(1):151. doi: 10.1186/s13287-017-0600-8.</citation>
      <PMID>28646903</PMID>
    </reference>
    <reference>
      <citation>Cruz FF, Borg ZD, Goodwin M, Sokocevic D, Wagner DE, Coffey A, Antunes M, Robinson KL, Mitsialis SA, Kourembanas S, Thane K, Hoffman AM, McKenna DH, Rocco PR, Weiss DJ. Systemic Administration of Human Bone Marrow-Derived Mesenchymal Stromal Cell Extracellular Vesicles Ameliorates Aspergillus Hyphal Extract-Induced Allergic Airway Inflammation in Immunocompetent Mice. Stem Cells Transl Med. 2015 Nov;4(11):1302-16. doi: 10.5966/sctm.2014-0280. Epub 2015 Sep 16.</citation>
      <PMID>26378259</PMID>
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    <reference>
      <citation>De Jong OG, Van Balkom BW, Schiffelers RM, Bouten CV, Verhaar MC. Extracellular vesicles: potential roles in regenerative medicine. Front Immunol. 2014 Dec 3;5:608. doi: 10.3389/fimmu.2014.00608. eCollection 2014.</citation>
      <PMID>25520717</PMID>
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      <citation>Kordelas L, Rebmann V, Ludwig AK, Radtke S, Ruesing J, Doeppner TR, Epple M, Horn PA, Beelen DW, Giebel B. MSC-derived exosomes: a novel tool to treat therapy-refractory graft-versus-host disease. Leukemia. 2014 Apr;28(4):970-3. doi: 10.1038/leu.2014.41. No abstract available.</citation>
      <PMID>24445866</PMID>
    </reference>
    <reference>
      <citation>Lanyu Z, Feilong H. Emerging role of extracellular vesicles in lung injury and inflammation. Biomed Pharmacother. 2019 May;113:108748. doi: 10.1016/j.biopha.2019.108748. Epub 2019 Mar 14.</citation>
      <PMID>30877881</PMID>
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    <reference>
      <citation>Lasser C, Jang SC, Lotvall J. Subpopulations of extracellular vesicles and their therapeutic potential. Mol Aspects Med. 2018 Apr;60:1-14. doi: 10.1016/j.mam.2018.02.002. Epub 2018 Feb 16.</citation>
      <PMID>29432782</PMID>
    </reference>
    <reference>
      <citation>Naji A, Eitoku M, Favier B, Deschaseaux F, Rouas-Freiss N, Suganuma N. Biological functions of mesenchymal stem cells and clinical implications. Cell Mol Life Sci. 2019 Sep;76(17):3323-3348. doi: 10.1007/s00018-019-03125-1. Epub 2019 May 4.</citation>
      <PMID>31055643</PMID>
    </reference>
    <reference>
      <citation>Raposo G, Stoorvogel W. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 2013 Feb 18;200(4):373-83. doi: 10.1083/jcb.201211138.</citation>
      <PMID>23420871</PMID>
    </reference>
    <reference>
      <citation>Sengupta V, Sengupta S, Lazo A, Woods P, Nolan A, Bremer N. Exosomes Derived from Bone Marrow Mesenchymal Stem Cells as Treatment for Severe COVID-19. Stem Cells Dev. 2020 Jun 15;29(12):747-754. doi: 10.1089/scd.2020.0080. Epub 2020 May 12.</citation>
      <PMID>32380908</PMID>
    </reference>
    <reference>
      <citation>Silva JD, de Castro LL, Braga CL, Oliveira GP, Trivelin SA, Barbosa-Junior CM, Morales MM, Dos Santos CC, Weiss DJ, Lopes-Pacheco M, Cruz FF, Rocco PRM. Mesenchymal Stromal Cells Are More Effective Than Their Extracellular Vesicles at Reducing Lung Injury Regardless of Acute Respiratory Distress Syndrome Etiology. Stem Cells Int. 2019 Aug 21;2019:8262849. doi: 10.1155/2019/8262849. eCollection 2019.</citation>
      <PMID>31531026</PMID>
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      <citation>Shi MM, Yang QY, Monsel A, Yan JY, Dai CX, Zhao JY, Shi GC, Zhou M, Zhu XM, Li SK, Li P, Wang J, Li M, Lei JG, Xu D, Zhu YG, Qu JM. Preclinical efficacy and clinical safety of clinical-grade nebulized allogenic adipose mesenchymal stromal cells-derived extracellular vesicles. J Extracell Vesicles. 2021 Aug;10(10):e12134. doi: 10.1002/jev2.12134. Epub 2021 Aug 14.</citation>
      <PMID>34429860</PMID>
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      <citation>D'Souza-Schorey C, Schorey JS. Regulation and mechanisms of extracellular vesicle biogenesis and secretion. Essays Biochem. 2018 May 15;62(2):125-133. doi: 10.1042/EBC20170078. Print 2018 May 15.</citation>
      <PMID>29666210</PMID>
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      <citation>Tieu A, Lalu MM, Slobodian M, Gnyra C, Fergusson DA, Montroy J, Burger D, Stewart DJ, Allan DS. An Analysis of Mesenchymal Stem Cell-Derived Extracellular Vesicles for Preclinical Use. ACS Nano. 2020 Aug 25;14(8):9728-9743. doi: 10.1021/acsnano.0c01363. Epub 2020 Aug 4.</citation>
      <PMID>32697573</PMID>
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      <citation>Wiklander OP, Nordin JZ, O'Loughlin A, Gustafsson Y, Corso G, Mager I, Vader P, Lee Y, Sork H, Seow Y, Heldring N, Alvarez-Erviti L, Smith CI, Le Blanc K, Macchiarini P, Jungebluth P, Wood MJ, Andaloussi SE. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. J Extracell Vesicles. 2015 Apr 20;4:26316. doi: 10.3402/jev.v4.26316. eCollection 2015.</citation>
      <PMID>25899407</PMID>
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      <citation>Zhou T, He C, Lai P, Yang Z, Liu Y, Xu H, Lin X, Ni B, Ju R, Yi W, Liang L, Pei D, Egwuagu CE, Liu X. miR-204-containing exosomes ameliorate GVHD-associated dry eye disease. Sci Adv. 2022 Jan 14;8(2):eabj9617. doi: 10.1126/sciadv.abj9617. Epub 2022 Jan 12.</citation>
      <PMID>35020440</PMID>
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      <citation>Zhu YG, Feng XM, Abbott J, Fang XH, Hao Q, Monsel A, Qu JM, Matthay MA, Lee JW. Human mesenchymal stem cell microvesicles for treatment of Escherichia coli endotoxin-induced acute lung injury in mice. Stem Cells. 2014 Jan;32(1):116-25. doi: 10.1002/stem.1504.</citation>
      <PMID>23939814</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 27, 2023</study_first_submitted>
    <study_first_submitted_qc>August 18, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 18, 2023</last_update_submitted>
    <last_update_submitted_qc>August 18, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>SARS-CoV-2</keyword>
    <keyword>intravenous therapy</keyword>
    <keyword>extracellular vesicles</keyword>
    <keyword>ARDS</keyword>
    <keyword>mesenchymal cells</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Severe Acute Respiratory Syndrome</mesh_term>
      <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>
      <mesh_term>Syndrome</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06002841
  org study id: EVs_2023
  nct id: NCT06002841
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This is a phase I/II, randomized, double-blind, placebo-controlled clinical trial that will
        evaluate the safety and potential efficacy of therapy with extracellular vesicles (EVs)
        obtained from mesenchymal stromal cells (MSCs), patients with moderate to severe acute
        respiratory distress syndrome due to COVID-19 or other etiology. Participants will be
        allocated to receive EVs obtained from MSCs or placebo (equal volume of Plasma-Lyte A).
        Blinding will cover the participants, the multidisciplinary intensive care team and the
        investigators.
  The studied population will consist of 15 patients diagnosed with acute respiratory failure
        syndrome admitted to the intensive care unit of Hospital São Rafael. This research aims to
        assess the safety and potential effectiveness of intravenous therapy using extracellular
        vesicles derived from mesenchymal cells in patients with moderate to severe acute respiratory
        distress syndrome. The treatment group will receive intravenous administration of
        extracellular vesicles obtained from mesenchymal cells, while the control group will receive
        a placebo.
  
        EV group: will consist of 10 participants who will receive two infusions of 25 mL of the
        investigational product (Plasma-Lyte A solution containing EVs obtained from MSCs),
        intravenously, at intervals of 48 h.
  
        Placebo group: will consist of 5 participants who will receive an equal volume of Plasma-Lyte
        A, intravenously, following the same schedule as the IV group: two infusions with an interval
        of 48 hours.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Parallel Assignment
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  masking description: The treatment and placebo solutions will be indistinguishable in terms of their appearance. Stringent protocols will be established to guarantee that the physicians responsible for assessing patient safety, evaluating efficacy outcomes, and conducting laboratory analyses will be blinded to the randomization codes.
  measure: Measure administration of extracellular vesicles (EVs) up to 28 days
  time frame: 28 days
  description: Measure as reported adverse events up to 28 days after treatment or placebo administration to evaluate safety of treatment
  measure: All-cause mortality
  time frame: Day 14 and day 28
  description: at days 14 and 28 after randomization;
  measure: Variation in the Ratio PaO2/FiO2
  time frame: Baseline, day 01, day 02 and day 07
  description: PaO2 (arterial partial pressure of oxygen)/FiO2 (fraction of inspired oxygen) on the day of randomization and at 24 hours, 48 hours and 7 days after the first infusion;
  measure: Variation in the SOFA index
  time frame: day 01, day 02, day 07, day 09, day 14 and day 29
  description: Variation in the SOFA index (Assessment of Sequential Organ Failure) at the time of randomization and during follow-up until discharge from the intensive care unit;
  measure: Exploratory laboratory analysis
  time frame: 30 days
  description: variation in total and differential laboratory analysis.
  measure: Duration of the period of hospitalization
  time frame: 30 days
  description: from hospital time in the intensive care unit (ICU)
  measure: Duration of the period of ICU ventilation
  time frame: 30 days
  description: If applicable,will be measured the time of mechanical ventilation.
  arm group label: EV group
  arm group type: Experimental
  description: will consist of 10 participants who will receive two infusions of 25 mL of the investigational product (Plasma-Lyte A solution containing EVs obtained from MSCs), intravenously, at intervals of 48 h.
  arm group label: Placebo group
  arm group type: Placebo Comparator
  description: will consist of 5 participants who will receive an equal volume of Plasma-Lyte A, intravenously, following the same schedule as the IV group: two infusions with an interval of 48 hours.
  intervention type: Biological
  intervention name: intravenous treatment with EVs
  description: intravenous treatment with extracellular vesicles
  arm group label: EV group
  intervention type: Biological
  intervention name: intravenous treatment with placebo solution
  description: intravenous treatment with placebo solution (without extracellular vesicles)
  arm group label: Placebo group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Bruno Souza, M.D
  role: Principal Investigator
  affiliation: Instituto D'Or de Pesquisa e Ensino (IDOR), Salvador, Brazil
  last name: Patrícia Rocco, M.D
  role: Principal Investigator
  affiliation: Universidade Federal do Rio de Janeiro (UFRJ)
  last name: Carolina Nonaka, phD
  phone: +55 (71) 3281-6970
  email: carolina.nonaka@hsr.com.br
  last name: Ingrid Barbosa, B.Sc
  phone: +551121098855
  email: nape@idor.org
  facility: 
  contact: 
  contact backup: 
  investigator: 
  investigator: 
  country: Brazil
  citation: Abels ER, Breakefield XO. Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake. Cell Mol Neurobiol. 2016 Apr;36(3):301-12. doi: 10.1007/s10571-016-0366-z. Epub 2016 Apr 6.
  PMID: 27053351
  citation: Alipoor SD, Mortaz E, Garssen J, Movassaghi M, Mirsaeidi M, Adcock IM. Exosomes and Exosomal miRNA in Respiratory Diseases. Mediators Inflamm. 2016;2016:5628404. doi: 10.1155/2016/5628404. Epub 2016 Sep 25.
  PMID: 27738390
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  responsible party type: Sponsor
  mesh term: Severe Acute Respiratory Syndrome
  mesh term: Respiratory Distress Syndrome
  mesh term: Respiratory Distress Syndrome, Newborn
  mesh term: Respiratory Insufficiency
  mesh term: Acute Lung Injury
  mesh term: Syndrome
  sharing ipd: No