<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/NCT01731795</url>
  </required_header>
  <id_info>
    <org_study_id>2012-000775-17</org_study_id>
    <nct_id>NCT01731795</nct_id>
  </id_info>
  <brief_title>Efficacy Study of Dexamethasone to Treat the Acute Respiratory Distress Syndrome</brief_title>
  <acronym>DEXA-ARDS</acronym>
  <official_title>A Comparative, Randomised Controlled Trial for Evaluating the Efficacy of Dexamethasone in the Treatment of Patients With Acute Respiratory Distress Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dr. Negrin University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fundación Mutua Madrileña</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Asociación Científica Pulmón y Ventilación Mecánica</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Dr. Negrin University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      BACKGROUND: Currently, there is no proven pharmacologic treatment for patients with the acute&#xD;
      respiratory distress syndrome (ARDS). Great interest remains in the use of corticosteroids&#xD;
      for the salvage of patients with severe acute lung injury in the early phase of their disease&#xD;
      process, a situation that that has not been evaluated in most published trials. Dexamethasone&#xD;
      has never been evaluated in ARDS in a randomized controlled fashion.&#xD;
&#xD;
      HYPOTHESIS AND OBJECTIVES: The investigators hypothesize that adjunctive treatment with&#xD;
      intravenous dexamethasone of patients with established ARDS might change the pulmonary and&#xD;
      systemic inflammatory response and thereby will increase the number of ventilator-free days&#xD;
      and will decrease the extremely high overall mortality. Our goal is to examine the effects of&#xD;
      dexamethasone on length of duration of mechanical ventilation (assessed by number of&#xD;
      ventilator-free days) and on mortality, in patients admitted into a network of Spanish&#xD;
      intensive care units (ICUs) who still meet ARDS criteria at 24 hours after ARDS onset.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The acute respiratory distress syndrome (ARDS) is an inflammatory disease process of the&#xD;
      lungs as a response to both direct and indirect insults, characterized clinically by severe&#xD;
      hypoxemia, reduced lung compliance, and bilateral radiographic infiltrates. ARDS is caused by&#xD;
      an insult to the alveolar-capillary membrane that results in increased permeability and&#xD;
      subsequent interstitial and alveolar edema. The mechanisms by which a wide variety of insults&#xD;
      can lead to this syndrome are not clear. It is useful to think of the pathogenesis of ARDS as&#xD;
      a result of two different pathways: a direct insult on lung cells and an indirect insult as a&#xD;
      result of an acute systemic inflammatory response.&#xD;
&#xD;
      Like any form of inflammation, acute lung injury during ARDS represents a complex process in&#xD;
      which multiple cellular signalling pathways can propagate or inhibit lung injury. Death has&#xD;
      traditionally been attributed to the underlying disease, the presence of sepsis and the&#xD;
      failure of vital organ systems other than the lung. The association of ARDS with multiple&#xD;
      system organ dysfunctions is not inevitable, but it certainly is common. It is postulated&#xD;
      that local injury to the lungs (pneumonia, trauma, aspiration, gas inhalation) could set up a&#xD;
      secondary diffuse inflammatory response resulting in damage to other organs.&#xD;
&#xD;
      Although much has evolved in our understanding of its pathogenesis and factors affecting&#xD;
      patient outcome, still there is no specific pharmacologic treatment for ARDS. Despite&#xD;
      advances in supportive measures and antibiotics, ARDS has a mortality rate of about 40-50% in&#xD;
      most series and it is associated with significant health care costs. Patients with ARDS&#xD;
      invariably require endotracheal intubation and mechanical ventilation (MV) to decrease the&#xD;
      work of breathing and to improve oxygen transport. To date the only proven, widely accepted&#xD;
      method of MV for ARDS is what is called &quot;lung protective ventilation&quot; using a low tidal&#xD;
      volume strategy plus positive end-expiratory pressure (PEEP).&#xD;
&#xD;
      Corticoids seemed to be an ideal therapy for the acute lung injury in ARDS, given their&#xD;
      potent anti-inflammatory and antifibrotic properties. They switch off genes that encode&#xD;
      pro-inflammatory cytokines and switch on genes that encode anti-inflammatory cytokines. It&#xD;
      has been reported that low doses of corticosteroids prevent an extended cytokine response and&#xD;
      might accelerate the resolution of pulmonary and systemic inflammation in pneumonia.&#xD;
&#xD;
      Dexamethasone has never been evaluated in ARDS in a randomized controlled fashion. However,&#xD;
      dexametasone has potent anti-inflammatory effects and weak mineralocorticoid effects compared&#xD;
      with other corticosteroids. Dexamethasone has a long-lasting effect, allowing for a&#xD;
      once-a-day regimen. Whether addition of dexamethasone to conventional supportive treatment&#xD;
      benefits ARDS patients is unknown, it has been used in patients with sepsis, septic shock,&#xD;
      pneumonia, trauma, and meningitis, all of them causes of ARDS.&#xD;
&#xD;
      The investigators justify the need of our study based on the positive results of two recent&#xD;
      clinical trials: (i) Meijvis et al (Lancet 2011) showed that dexamethasone (5 mg/day) for 4&#xD;
      days was able to reduce length of hospital stay in 304 patients with bacterial pneumonia when&#xD;
      added to the conventional treatment; (ii) Azoulay et al (Eur Respir J 2011) showed that&#xD;
      dexamethasone (10 mg/6h), when added to chemotherapy and conventional ICU management, caused&#xD;
      less respiratory deterioration and lower ICU mortality in 40 patients with acute lung injury&#xD;
      resulting from leukaemia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 28, 2013</start_date>
  <completion_date type="Actual">February 12, 2019</completion_date>
  <primary_completion_date type="Actual">February 12, 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ventilator free-days</measure>
    <time_frame>28 days</time_frame>
    <description>Number of ventilator free-days (VFDs) at Day 28 (defined as days alive and free from mechanical ventilation at day 28 after intubation. For subjects ventilated ≥28 days and for subjects who die, VFD is 0.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>60 days</time_frame>
    <description>All-cause mortality at Day 60 after enrolment.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>organ failure</measure>
    <time_frame>ICU discharge</time_frame>
    <description>Number of extrapulmonary organ system failures</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">277</enrollment>
  <condition>Acute Respiratory Distress Syndrome</condition>
  <arm_group>
    <arm_group_label>No dexamethasone</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients will be treated with conventional treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dexamethasone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Conventional treatment plus dexamethasone</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Dexamethasone (20 mg/iv/daily/from Day 1 of randomization during 5 days, followed by 10 mg/iv/daily/ from Day 6 to 10 of randomization)</description>
    <arm_group_label>Dexamethasone</arm_group_label>
    <other_name>Dexamethasone Indukern</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥18 years old&#xD;
&#xD;
          -  Patients must have acute onset of ARDS, as defined by the American-European Consensus&#xD;
             Conference (AECC) criteria for ARDS: (i) having an initiating clinical condition&#xD;
             (pneumonia, aspiration, inhalation injury, sepsis, trauma, acute pancreatitis, etc.;&#xD;
             (ii) bilateral infiltrates on frontal chest radiograph; (iii) absence of left atrial&#xD;
             hypertension, a pulmonary capillary wedge pressure (PCWP) less than 18 mm Hg, or no&#xD;
             clinical signs of left heart failure; (iv) severe hypoxemia (a PaO2/FIO2 &lt;200 mm Hg,&#xD;
             regardless of FIO2 or positive end-expiratory pressure (PEEP)&#xD;
&#xD;
          -  Be intubated and mechanically ventilated&#xD;
&#xD;
          -  Have provided signed written informed consent from the patient or the patient's&#xD;
             personal legal representative&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Be a woman known to be pregnant or lactating&#xD;
&#xD;
          -  Take part in another experimental treatment protocol (simultaneously)&#xD;
&#xD;
          -  Brain death&#xD;
&#xD;
          -  Terminal-stage cancer or other terminal disease&#xD;
&#xD;
          -  Having do-not-resuscitate orders&#xD;
&#xD;
          -  Being immune-compromised&#xD;
&#xD;
          -  Receiving corticosteroids or immunosuppressive drugs&#xD;
&#xD;
          -  Patients in whom more than 24 hours had elapsed after initially meeting the AECC ARDS&#xD;
             criteria before consent and results of initial standard ventilator settings could be&#xD;
             obtained.&#xD;
&#xD;
          -  Have severe chronic obstructive pulmonary disease (COPD)&#xD;
&#xD;
          -  Have congestive heart failure&#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>Jesús Villar, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Research Unit, Hospital Universitario Dr. Negrín, Las Palmas, Spain</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Universitario Dr. Negrin</name>
      <address>
        <city>Las Palmas de Gran Canaria</city>
        <zip>35010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico de Valencia</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>November 18, 2012</study_first_submitted>
  <study_first_submitted_qc>November 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2012</study_first_posted>
  <last_update_submitted>February 14, 2019</last_update_submitted>
  <last_update_submitted_qc>February 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 18, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dr. Negrin University Hospital</investigator_affiliation>
    <investigator_full_name>Jesus Villar</investigator_full_name>
    <investigator_title>Director of Research</investigator_title>
  </responsible_party>
  <keyword>acute respiratory distress syndrome, mechanical ventilation</keyword>
  <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>Acute Lung Injury</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
    <mesh_term>Dexamethasone acetate</mesh_term>
    <mesh_term>BB 1101</mesh_term>
  </intervention_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/NCT01731795
org study id: 2012-000775-17
nct id: NCT01731795
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
BACKGROUND: Currently, there is no proven pharmacologic treatment for patients with the acute
      respiratory distress syndrome (ARDS). Great interest remains in the use of corticosteroids
      for the salvage of patients with severe acute lung injury in the early phase of their disease
      process, a situation that that has not been evaluated in most published trials. Dexamethasone
      has never been evaluated in ARDS in a randomized controlled fashion.

      HYPOTHESIS AND OBJECTIVES: The investigators hypothesize that adjunctive treatment with
      intravenous dexamethasone of patients with established ARDS might change the pulmonary and
      systemic inflammatory response and thereby will increase the number of ventilator-free days
      and will decrease the extremely high overall mortality. Our goal is to examine the effects of
      dexamethasone on length of duration of mechanical ventilation (assessed by number of
      ventilator-free days) and on mortality, in patients admitted into a network of Spanish
      intensive care units (ICUs) who still meet ARDS criteria at 24 hours after ARDS onset.
The acute respiratory distress syndrome (ARDS) is an inflammatory disease process of the
      lungs as a response to both direct and indirect insults, characterized clinically by severe
      hypoxemia, reduced lung compliance, and bilateral radiographic infiltrates. ARDS is caused by
      an insult to the alveolar-capillary membrane that results in increased permeability and
      subsequent interstitial and alveolar edema. The mechanisms by which a wide variety of insults
      can lead to this syndrome are not clear. It is useful to think of the pathogenesis of ARDS as
      a result of two different pathways: a direct insult on lung cells and an indirect insult as a
      result of an acute systemic inflammatory response.

      Like any form of inflammation, acute lung injury during ARDS represents a complex process in
      which multiple cellular signalling pathways can propagate or inhibit lung injury. Death has
      traditionally been attributed to the underlying disease, the presence of sepsis and the
      failure of vital organ systems other than the lung. The association of ARDS with multiple
      system organ dysfunctions is not inevitable, but it certainly is common. It is postulated
      that local injury to the lungs (pneumonia, trauma, aspiration, gas inhalation) could set up a
      secondary diffuse inflammatory response resulting in damage to other organs.

      Although much has evolved in our understanding of its pathogenesis and factors affecting
      patient outcome, still there is no specific pharmacologic treatment for ARDS. Despite
      advances in supportive measures and antibiotics, ARDS has a mortality rate of about 40-50% in
      most series and it is associated with significant health care costs. Patients with ARDS
      invariably require endotracheal intubation and mechanical ventilation (MV) to decrease the
      work of breathing and to improve oxygen transport. To date the only proven, widely accepted
      method of MV for ARDS is what is called "lung protective ventilation" using a low tidal
      volume strategy plus positive end-expiratory pressure (PEEP).

      Corticoids seemed to be an ideal therapy for the acute lung injury in ARDS, given their
      potent anti-inflammatory and antifibrotic properties. They switch off genes that encode
      pro-inflammatory cytokines and switch on genes that encode anti-inflammatory cytokines. It
      has been reported that low doses of corticosteroids prevent an extended cytokine response and
      might accelerate the resolution of pulmonary and systemic inflammation in pneumonia.

      Dexamethasone has never been evaluated in ARDS in a randomized controlled fashion. However,
      dexametasone has potent anti-inflammatory effects and weak mineralocorticoid effects compared
      with other corticosteroids. Dexamethasone has a long-lasting effect, allowing for a
      once-a-day regimen. Whether addition of dexamethasone to conventional supportive treatment
      benefits ARDS patients is unknown, it has been used in patients with sepsis, septic shock,
      pneumonia, trauma, and meningitis, all of them causes of ARDS.

      The investigators justify the need of our study based on the positive results of two recent
      clinical trials: (i) Meijvis et al (Lancet 2011) showed that dexamethasone (5 mg/day) for 4
      days was able to reduce length of hospital stay in 304 patients with bacterial pneumonia when
      added to the conventional treatment; (ii) Azoulay et al (Eur Respir J 2011) showed that
      dexamethasone (10 mg/6h), when added to chemotherapy and conventional ICU management, caused
      less respiratory deterioration and lower ICU mortality in 40 patients with acute lung injury
      resulting from leukaemia.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Ventilator free-days
time frame: 28 days
description: Number of ventilator free-days (VFDs) at Day 28 (defined as days alive and free from mechanical ventilation at day 28 after intubation. For subjects ventilated ≥28 days and for subjects who die, VFD is 0.
measure: Mortality
time frame: 60 days
description: All-cause mortality at Day 60 after enrolment.
measure: organ failure
time frame: ICU discharge
description: Number of extrapulmonary organ system failures
arm group label: No dexamethasone
arm group type: No Intervention
description: Patients will be treated with conventional treatment
arm group label: Dexamethasone
arm group type: Active Comparator
description: Conventional treatment plus dexamethasone
intervention type: Drug
intervention name: Dexamethasone
description: Dexamethasone (20 mg/iv/daily/from Day 1 of randomization during 5 days, followed by 10 mg/iv/daily/ from Day 6 to 10 of randomization)
arm group label: Dexamethasone
other name: Dexamethasone Indukern
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Jesús Villar, MD, PhD
role: Principal Investigator
affiliation: Research Unit, Hospital Universitario Dr. Negrín, Las Palmas, Spain
facility: 
facility: 
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Dr. Negrin University Hospital
investigator full name: Jesus Villar
investigator title: Director of Research
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury
mesh term: Syndrome
mesh term: Dexamethasone
mesh term: Dexamethasone acetate
mesh term: BB 1101
sharing ipd: No