<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/NCT02977572</url>
  </required_header>
  <id_info>
    <org_study_id>HGU Castellon-002</org_study_id>
    <nct_id>NCT02977572</nct_id>
  </id_info>
  <brief_title>Non-invasive Ventilation Versus Continuous Positive Airway Pressure in Cardiogenic Pulmonary Edema</brief_title>
  <official_title>Non-Invasive Mechanical Ventilation Versus Continuous Positive Airway Pressure Relating to Cardiogenic Pulmonary Edema in an Intensive Care Unit</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital General Universitario de Castellón</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital General Universitario de Castellón</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the present study was to demonstrate that an Non-Invasive Ventilation (NIV)&#xD;
      performs better than a Continuous Positive Airway Pressure (CPAP) in the management of&#xD;
      Cardiogenic Pulmonary Edema (CPE) within an Intensive Care Unit (ICU) setting.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Continuous Positive Airway Pressure (CPAP) and Non-Invasive Ventilation (NIV), has played a&#xD;
      decisive role in the treatment of Acute Respiratory Failure (ARF) secondary to Cardiogenic&#xD;
      Pulmonary Edema (CPE). The use of either CPAP or NIV has resulted in greater clinical&#xD;
      improvements than the ones that have been previously obtained by using a standard medical&#xD;
      therapy. Although there is a strong indication for NIV in hypercapnic patients, the situation&#xD;
      whether NIV is superior to CPAP remains unclear, and hence, both have been recommended.&#xD;
&#xD;
      NIV and CPAP have both been successfully used in patients admitted to an Intensive Care Unit&#xD;
      (ICU) suffering from CPE. However, few trials have been published on the ICU scenario. In&#xD;
      addition, Acute Coronary Syndrome (ACS) has been considered to be an exclusion criterion in&#xD;
      several trials.&#xD;
&#xD;
      At the time of the onset of CPE, either in the Emergency Department (ED) or in the ward, all&#xD;
      participants received a standard medical therapy (oxygen through a Venturi mask, morphine,&#xD;
      intravenous nitroglycerin if their systolic blood pressure &gt;160 mmHg, together with loop&#xD;
      diuretics), all at the discretion of the attending physician. In the absence of a clinical&#xD;
      improvement [dyspnea, respiratory rate &gt;25rpm, transcutaneous arterial oxygen saturation&#xD;
      (SaO2) &lt;90%], the participant was admitted to the ICU and assigned to the NIV group or the&#xD;
      CPAP group, regardless of the treatment that they had received in the ED. The participants&#xD;
      that were admitted to the ICU at the onset of CPE were randomised without a trial of medical&#xD;
      treatment. The assignment of each group was performed by opening a sealed envelope following&#xD;
      a prior randomisation by using a computerised system.&#xD;
&#xD;
      Statistical. A comparative analysis was conducted by using the Student's t-test or the&#xD;
      Mann-Whitney test for a comparison of the quantitative variables for the parametric and&#xD;
      non-parametric characteristics, respectively. For the qualitative variables, the&#xD;
      investigators used the Chi-Square statistic or Fisher's exact test. A statistical&#xD;
      significance was reached if P&lt;0.05. The cumulative probability of survival was compared by&#xD;
      using a Kaplan-Meier estimation of survival and a Log-Rank Test to compare both of the&#xD;
      groups.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2007</start_date>
  <completion_date type="Actual">January 2011</completion_date>
  <primary_completion_date type="Actual">December 2010</primary_completion_date>
  <phase>N/A</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>Need for an Endotracheal Intubation Within Seven Days After Onset of Cardiopulmonary Edema at the Intensive Care Unit</measure>
    <time_frame>Whitin seven days after onset of cardiopulmonary edema at the Intensive Care Unit</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of the Ventilation</measure>
    <time_frame>Time (hours) from start of ventilation until the removal of both devices because of improve or failure</time_frame>
    <description>Period of ventilation (either noninvasive ventilation or continouos positive airway pressure) while the patient suffers from acute respiratory failure secondary to cardiopulmonary edema</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilator Acquired Pneumonia</measure>
    <time_frame>Pulmonary infection at intensive care unit diagnosed until 72 hours after removal of ventilation</time_frame>
    <description>Pulmonary infections (%) during stay at intensive care unit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute Renal Failure</measure>
    <time_frame>Acute Renal Failure during intensive care unit stay (at discharge from intensive care unit)</time_frame>
    <description>Development of acute renal failure measured as increase of level of creatinine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Stay at Intensive Care Unit</measure>
    <time_frame>Length of stay (days) at Intensive Care Unit at discharge from intensive care unit.</time_frame>
    <description>Length of stay of the patient at Intensive Care Unit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Hospital Stay</measure>
    <time_frame>Length of stay (days) at hospital at discharge from hospital</time_frame>
    <description>All the time (days) the patient stays at the hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intensive Care Unit Mortality</measure>
    <time_frame>Mortality (%) at Intensive Care Unit at discharge from intensive care unit</time_frame>
    <description>Mortality (%) at Intensive Care Unit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>28th Day Mortality</measure>
    <time_frame>Mortality within 28 days of randomization</time_frame>
    <description>Mortility of patients within of the first 28 days after randomization (either at intensive car unit or at hospital)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital Mortality</measure>
    <time_frame>Mortality (%) at Hospital at discharge from hospital</time_frame>
    <description>Mortality during hospital stay (including at Intensive care mortality)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">114</enrollment>
  <condition>Cardiogenic Pulmonary Oedema</condition>
  <arm_group>
    <arm_group_label>Non-Invasive ventilation (NIV group)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>For the NIV group, a BiPAP Vision was used, by setting the Inspiratory Positive Airway Pressure (IPAP) at a level that was required to achieve a tidal volume of approximately 8-10 ml/kg. Also an Expiratory Positive Airway Pressure (EPAP) was set at a minimum of 5 cmH20 during the first hour, gradually increasing until there was a clinical improvement. Fraction inspiratory of oxygen (FiO2) was applied to maintain a transcutaneous arterial oxygen saturation (SaO2) of 92%-94%. NIV was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Continuous Positive AirwayPressure CPAP</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The CPAP was applied by using a flow generator with adjustable fractional inspired oxygen (FiO2). This was connected to the Positive End-Expiratory Pressure (PEEP) valve that was placed in the face mask. In the second instance, the CPAP system that was used was a Boussignac CPAP System Flow Jet. The Boussignac valve takes gas from a single source and splits it in order to create four high flow jets. These jets converge in the chamber creating a virtual valve. A initial level of 5cmH20 of PEEP was recommended for the first hour of ventilation, with subsequent increments (up to 15cmH20) until a clinical improvement was obtained. CPAP was continuously applied until there was a clinical and/or a gasometrical improvement, at which time it was replaced by a Venturi mask.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Non-Invasive Ventilation</intervention_name>
    <description>In arm description</description>
    <arm_group_label>Non-Invasive ventilation (NIV group)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Continuous Positive AirwayPressure CPAP</intervention_name>
    <description>In arm description</description>
    <arm_group_label>Continuous Positive AirwayPressure CPAP</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants suffering from CPE, defined as having the presence of dyspnea,&#xD;
             respiratory rate &gt;25 breaths/minute, the use of accessory respiratory muscles,&#xD;
             cyanosis, cold sweats, bilateral crackles and/or wheezing on pulmonary auscultation,&#xD;
             hypoxaemia, hypertension, and a predominance of bilateral pulmonary infiltrates upon a&#xD;
             chest radiography (if available).&#xD;
&#xD;
          -  The potential causes of CPE have been understood to be Acute Coronary Syndrome (ACS)&#xD;
             with or without a persistent ST-segment elevation, hypertensive emergency,&#xD;
             valvulopathy, acute arrhythmia, endocarditis, or decompensation due to a chronic heart&#xD;
             failure.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The exclusion criteria were: a refused consent, the patient's inability to cooperate,&#xD;
             severe encephalopathy (Glasgow Coma Score &lt;10)&#xD;
&#xD;
          -  Anatomical difficulty when adjusting the face mask, non-cardiogenic Acute Respiratory&#xD;
             Failure (pneumonia, blunt chest trauma, or chronic obstructive pulmonary disease)&#xD;
&#xD;
          -  Respiratory or cardiac arrest on admission, together with the need for an immediate&#xD;
             intubation.&#xD;
&#xD;
          -  Specific cardiac contraindications were also considered, including: cardiogenic shock&#xD;
             on admission established by systolic blood pressure (SBP) &lt;90 mmHg, or a dependence on&#xD;
             vasoactive drugs (norepinephrine &gt;0.5 µg/kg/min).&#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>ALBERTO BELENGUER-MUNCHARAZ, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>INTENSIVE CARE UNIT. HOSPITAL GENERAL CASTELLO</affiliation>
  </overall_official>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>November 25, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 30, 2016</study_first_posted>
  <results_first_submitted>December 9, 2016</results_first_submitted>
  <results_first_submitted_qc>June 22, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">July 21, 2017</results_first_posted>
  <last_update_submitted>June 22, 2017</last_update_submitted>
  <last_update_submitted_qc>June 22, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 21, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital General Universitario de Castellón</investigator_affiliation>
    <investigator_full_name>ALBERTO BELENGUER MUNCHARAZ</investigator_full_name>
    <investigator_title>MD, Phd, INTENSIVE CARE UNIT</investigator_title>
  </responsible_party>
  <keyword>Non-invasive ventilation,</keyword>
  <keyword>continuous positive airway pressure</keyword>
  <keyword>cardiogenic pulmonary oedema,</keyword>
  <keyword>acute respiratory failure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Edema</mesh_term>
    <mesh_term>Edema</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Non-Invasive Ventilation (NIV Group)</title>
          <description>For the Non-Invasive ventilation group, a BiPAP Vision was used, by setting the Inspiratory Positive Airway Pressure (IPAP) at a level that was required to achieve a tidal volume of approximately 8-10 ml/kg. Also an Expiratory Positive Airway Pressure (EPAP) was set at a minimum of 5 cmH20 during the first hour, gradually increasing until there was a clinical improvement. Fraction inspiratory of oxygen (FiO2) was applied to maintain a transcutaneous arterial oxygen saturation (SaO2) of 92%-94%. NIV was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Non-Invasive Ventilation: In arm description</description>
        </group>
        <group group_id="P2">
          <title>Continuous Positive Airway Pressure (CPAP) Group</title>
          <description>The Continuous Positive Airway Pressure was applied by using a flow generator that was capable of delivering a flow of 140 Liter/minute, with adjustable fractional inspired oxygen that ranged from 0.3 to 1.0. This was connected to the Positive End-Expiratory Pressure valve that was placed in the face mask. In the second instance, the CPAP system that was used was a Boussignac CPAP System. The Boussignac valve takes gas from a single source and splits it in order to create four high flow jets. These jets converge in the chamber creating a turbulence which creates a virtual valve. A minimal initial level of 5cmH20 of PEEP was recommended for the first hour of the CPAP, with subsequent increments (up to 15cmH20) until a clinical improvement was obtained. CPAP was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Continuous Positive Airway Pressure: In arm description</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="58"/>
                <participants group_id="P2" count="56"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="56"/>
                <participants group_id="P2" count="54"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Exclusion criterion</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Continuous Positive Airway Pressure (CPAP) Group</title>
          <description>The CPAP was applied by using a flow generator that was capable of delivering a flow of 140 Liter /minute, with adjustable fractional inspired oxygen (FiO2) that ranged from 0.3 to 1.0. This was connected to the Positive End-Expiratory Pressure (PEEP) valve that was placed in the face mask. In the second instance, the CPAP system that was used was a Boussignac CPAP System Flow Jet. The Boussignac valve takes gas from a single source and splits it in order to create four high flow jets. These jets converge in the chamber creating a turbulence which creates a virtual valve. A minimal initial level of 5cmH20 of PEEP was recommended for the first hour of the CPAP, with subsequent increments (up to 15cmH20) until a clinical improvement was obtained. CPAP was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Continuous Positive Airway Pressure: In arm description</description>
        </group>
        <group group_id="B2">
          <title>Non-Invasive Ventilation (NIV Group)</title>
          <description>For the NIV group, a BiPAP Vision was used, by setting the Inspiratory Positive Airway Pressure (IPAP) at a level that was required to achieve a tidal volume of approximately 8-10 ml/kg. Also an Expiratory Positive Airway Pressure (EPAP) was set at a minimum of 5 cmH20 during the first hour, gradually increasing until there was a clinical improvement. Fraction inspiratory of oxygen (FiO2) was applied to maintain a transcutaneous arterial oxygen saturation (SaO2) of 92%-94%. NIV was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Non-Invasive Ventilation: In arm description</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="54"/>
            <count group_id="B2" value="56"/>
            <count group_id="B3" value="110"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Need for an Endotracheal Intubation Within Seven Days After Onset of Cardiopulmonary Edema at the Intensive Care Unit</title>
        <time_frame>Whitin seven days after onset of cardiopulmonary edema at the Intensive Care Unit</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Non-Invasive Ventilation (NIV Group)</title>
            <description>For the NIV group, a BiPAP Vision was used, by setting the Inspiratory Positive Airway Pressure (IPAP) at a level that was required to achieve a tidal volume of approximately 8-10 ml/kg. Also an Expiratory Positive Airway Pressure (EPAP) was set at a minimum of 5 cmH20 during the first hour, gradually increasing until there was a clinical improvement. Fraction inspiratory of oxygen (FiO2) was applied to maintain a transcutaneous arterial oxygen saturation (SaO2) of 92%-94%. NIV was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Non-Invasive Ventilation: In arm description</description>
          </group>
          <group group_id="O2">
            <title>Continuous Positive Airway Pressure (CPAP) Group</title>
            <description>The CPAP was applied by using a flow generator that was capable of delivering a flow of 140 Liter /minute, with adjustable fractional inspired oxygen (FiO2) that ranged from 0.3 to 1.0. This was connected to the Positive End-Expiratory Pressure (PEEP) valve that was placed in the face mask. In the second instance, the CPAP system that was used was a Boussignac CPAP System Flow Jet. The Boussignac valve takes gas from a single source and splits it in order to create four high flow jets. These jets converge in the chamber creating a turbulence which creates a virtual valve. A minimal initial level of 5cmH20 of PEEP was recommended for the first hour of the CPAP, with subsequent increments (up to 15cmH20) until a clinical improvement was obtained. CPAP was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Continuous Positive Airway Pressure: In arm description</description>
          </group>
        </group_list>
        <measure>
          <title>Need for an Endotracheal Intubation Within Seven Days After Onset of Cardiopulmonary Edema at the Intensive Care Unit</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Based upon previous results, the investigators considered that the need for an intubation could be reduced by 15% [19% in the CPAP group (control) vs. 4% in the NIV group (study)]. The estimated sample size was 55 participants in each group (confidence interval [1-α] = 90% and power [1-β] = 85%).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>1.000</p_value>
            <method>Chi-squared</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of the Ventilation</title>
        <description>Period of ventilation (either noninvasive ventilation or continouos positive airway pressure) while the patient suffers from acute respiratory failure secondary to cardiopulmonary edema</description>
        <time_frame>Time (hours) from start of ventilation until the removal of both devices because of improve or failure</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Non-Invasive Ventilation (NIV Group)</title>
            <description>For the Non-Invasive ventilation group, a BiPAP Vision was used, by setting the Inspiratory Positive Airway Pressure (IPAP) at a level that was required to achieve a tidal volume of approximately 8-10 ml/kg. Also an Expiratory Positive Airway Pressure (EPAP) was set at a minimum of 5 cmH20 during the first hour, gradually increasing until there was a clinical improvement. Fraction inspiratory of oxygen (FiO2) was applied to maintain a transcutaneous arterial oxygen saturation (SaO2) of 92%-94%. NIV was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Non-Invasive Ventilation: In arm description</description>
          </group>
          <group group_id="O2">
            <title>Continuous Positive Airway Pressure (CPAP) Group</title>
            <description>The Continuous Positive Airway Pressure was applied by using a flow generator that was capable of delivering a flow of 140 Liter/minute, with adjustable fractional inspired oxygen that ranged from 0.3 to 1.0. This was connected to the Positive End-Expiratory Pressure valve that was placed in the face mask. In the second instance, the CPAP system that was used was a Boussignac CPAP System. The Boussignac valve takes gas from a single source and splits it in order to create four high flow jets. These jets converge in the chamber creating a turbulence which creates a virtual valve. A minimal initial level of 5cmH20 of PEEP was recommended for the first hour of the CPAP, with subsequent increments (up to 15cmH20) until a clinical improvement was obtained. CPAP was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Continuous Positive Airway Pressure: In arm description</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of the Ventilation</title>
          <description>Period of ventilation (either noninvasive ventilation or continouos positive airway pressure) while the patient suffers from acute respiratory failure secondary to cardiopulmonary edema</description>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16" lower_limit="6" upper_limit="34"/>
                    <measurement group_id="O2" value="10" lower_limit="2" upper_limit="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ventilator Acquired Pneumonia</title>
        <description>Pulmonary infections (%) during stay at intensive care unit</description>
        <time_frame>Pulmonary infection at intensive care unit diagnosed until 72 hours after removal of ventilation</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Continuous Positive Airway Pressure (CPAP) Group</title>
            <description>The CPAP was applied by using a flow generator that was capable of delivering a flow of 140 Liter /minute, with adjustable fractional inspired oxygen (FiO2) that ranged from 0.3 to 1.0. This was connected to the Positive End-Expiratory Pressure (PEEP) valve that was placed in the face mask. In the second instance, the CPAP system that was used was a Boussignac CPAP System Flow Jet. The Boussignac valve takes gas from a single source and splits it in order to create four high flow jets. These jets converge in the chamber creating a turbulence which creates a virtual valve. A minimal initial level of 5cmH20 of PEEP was recommended for the first hour of the CPAP, with subsequent increments (up to 15cmH20) until a clinical improvement was obtained. CPAP was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Continuous Positive Airway Pressure: In arm description</description>
          </group>
          <group group_id="O2">
            <title>Non-Invasive Ventilation (NIV Group)</title>
            <description>For the NIV group, a BiPAP Vision was used, by setting the Inspiratory Positive Airway Pressure (IPAP) at a level that was required to achieve a tidal volume of approximately 8-10 ml/kg. Also an Expiratory Positive Airway Pressure (EPAP) was set at a minimum of 5 cmH20 during the first hour, gradually increasing until there was a clinical improvement. Fraction inspiratory of oxygen (FiO2) was applied to maintain a transcutaneous arterial oxygen saturation (SaO2) of 92%-94%. NIV was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Non-Invasive Ventilation: In arm description</description>
          </group>
        </group_list>
        <measure>
          <title>Ventilator Acquired Pneumonia</title>
          <description>Pulmonary infections (%) during stay at intensive care unit</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Acute Renal Failure</title>
        <description>Development of acute renal failure measured as increase of level of creatinine</description>
        <time_frame>Acute Renal Failure during intensive care unit stay (at discharge from intensive care unit)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Non-Invasive Ventilation (NIV Group)</title>
            <description>For the Non-Invasive ventilation group, a BiPAP Vision was used, by setting the Inspiratory Positive Airway Pressure (IPAP) at a level that was required to achieve a tidal volume of approximately 8-10 ml/kg. Also an Expiratory Positive Airway Pressure (EPAP) was set at a minimum of 5 cmH20 during the first hour, gradually increasing until there was a clinical improvement. Fraction inspiratory of oxygen (FiO2) was applied to maintain a transcutaneous arterial oxygen saturation (SaO2) of 92%-94%. NIV was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Non-Invasive Ventilation: In arm description</description>
          </group>
          <group group_id="O2">
            <title>Continuous Positive Airway Pressure (CPAP) Group</title>
            <description>The Continuous Positive Airway Pressure was applied by using a flow generator that was capable of delivering a flow of 140 Liter/minute, with adjustable fractional inspired oxygen that ranged from 0.3 to 1.0. This was connected to the Positive End-Expiratory Pressure valve that was placed in the face mask. In the second instance, the CPAP system that was used was a Boussignac CPAP System. The Boussignac valve takes gas from a single source and splits it in order to create four high flow jets. These jets converge in the chamber creating a turbulence which creates a virtual valve. A minimal initial level of 5cmH20 of PEEP was recommended for the first hour of the CPAP, with subsequent increments (up to 15cmH20) until a clinical improvement was obtained. CPAP was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Continuous Positive Airway Pressure: In arm description</description>
          </group>
        </group_list>
        <measure>
          <title>Acute Renal Failure</title>
          <description>Development of acute renal failure measured as increase of level of creatinine</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Length of Stay at Intensive Care Unit</title>
        <description>Length of stay of the patient at Intensive Care Unit</description>
        <time_frame>Length of stay (days) at Intensive Care Unit at discharge from intensive care unit.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Non-Invasive Ventilation (NIV Group)</title>
            <description>For the Non-Invasive ventilation group, a BiPAP Vision was used, by setting the Inspiratory Positive Airway Pressure (IPAP) at a level that was required to achieve a tidal volume of approximately 8-10 ml/kg. Also an Expiratory Positive Airway Pressure (EPAP) was set at a minimum of 5 cmH20 during the first hour, gradually increasing until there was a clinical improvement. Fraction inspiratory of oxygen (FiO2) was applied to maintain a transcutaneous arterial oxygen saturation (SaO2) of 92%-94%. NIV was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Non-Invasive Ventilation: In arm description</description>
          </group>
          <group group_id="O2">
            <title>Continuous Positive Airway Pressure (CPAP) Group</title>
            <description>The Continuous Positive Airway Pressure was applied by using a flow generator that was capable of delivering a flow of 140 Liter/minute, with adjustable fractional inspired oxygen that ranged from 0.3 to 1.0. This was connected to the Positive End-Expiratory Pressure valve that was placed in the face mask. In the second instance, the CPAP system that was used was a Boussignac CPAP System. The Boussignac valve takes gas from a single source and splits it in order to create four high flow jets. These jets converge in the chamber creating a turbulence which creates a virtual valve. A minimal initial level of 5cmH20 of PEEP was recommended for the first hour of the CPAP, with subsequent increments (up to 15cmH20) until a clinical improvement was obtained. CPAP was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Continuous Positive Airway Pressure: In arm description</description>
          </group>
        </group_list>
        <measure>
          <title>Length of Stay at Intensive Care Unit</title>
          <description>Length of stay of the patient at Intensive Care Unit</description>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3" lower_limit="2" upper_limit="6"/>
                    <measurement group_id="O2" value="4" lower_limit="1" upper_limit="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Length of Hospital Stay</title>
        <description>All the time (days) the patient stays at the hospital</description>
        <time_frame>Length of stay (days) at hospital at discharge from hospital</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Non-Invasive Ventilation (NIV Group)</title>
            <description>For the Non-Invasive ventilation group, a BiPAP Vision was used, by setting the Inspiratory Positive Airway Pressure (IPAP) at a level that was required to achieve a tidal volume of approximately 8-10 ml/kg. Also an Expiratory Positive Airway Pressure (EPAP) was set at a minimum of 5 cmH20 during the first hour, gradually increasing until there was a clinical improvement. Fraction inspiratory of oxygen (FiO2) was applied to maintain a transcutaneous arterial oxygen saturation (SaO2) of 92%-94%. NIV was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Non-Invasive Ventilation: In arm description</description>
          </group>
          <group group_id="O2">
            <title>Continuous Positive Airway Pressure (CPAP) Group</title>
            <description>The Continuous Positive Airway Pressure was applied by using a flow generator that was capable of delivering a flow of 140 Liter/minute, with adjustable fractional inspired oxygen that ranged from 0.3 to 1.0. This was connected to the Positive End-Expiratory Pressure valve that was placed in the face mask. In the second instance, the CPAP system that was used was a Boussignac CPAP System. The Boussignac valve takes gas from a single source and splits it in order to create four high flow jets. These jets converge in the chamber creating a turbulence which creates a virtual valve. A minimal initial level of 5cmH20 of PEEP was recommended for the first hour of the CPAP, with subsequent increments (up to 15cmH20) until a clinical improvement was obtained. CPAP was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Continuous Positive Airway Pressure: In arm description</description>
          </group>
        </group_list>
        <measure>
          <title>Length of Hospital Stay</title>
          <description>All the time (days) the patient stays at the hospital</description>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12" lower_limit="7" upper_limit="17"/>
                    <measurement group_id="O2" value="14" lower_limit="6" upper_limit="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Intensive Care Unit Mortality</title>
        <description>Mortality (%) at Intensive Care Unit</description>
        <time_frame>Mortality (%) at Intensive Care Unit at discharge from intensive care unit</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Non-Invasive Ventilation (NIV Group)</title>
            <description>For the Non-Invasive ventilation group, a BiPAP Vision was used, by setting the Inspiratory Positive Airway Pressure (IPAP) at a level that was required to achieve a tidal volume of approximately 8-10 ml/kg. Also an Expiratory Positive Airway Pressure (EPAP) was set at a minimum of 5 cmH20 during the first hour, gradually increasing until there was a clinical improvement. Fraction inspiratory of oxygen (FiO2) was applied to maintain a transcutaneous arterial oxygen saturation (SaO2) of 92%-94%. NIV was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Non-Invasive Ventilation: In arm description</description>
          </group>
          <group group_id="O2">
            <title>Continuous Positive Airway Pressure (CPAP) Group</title>
            <description>The Continuous Positive Airway Pressure was applied by using a flow generator that was capable of delivering a flow of 140 Liter/minute, with adjustable fractional inspired oxygen that ranged from 0.3 to 1.0. This was connected to the Positive End-Expiratory Pressure valve that was placed in the face mask. In the second instance, the CPAP system that was used was a Boussignac CPAP System. The Boussignac valve takes gas from a single source and splits it in order to create four high flow jets. These jets converge in the chamber creating a turbulence which creates a virtual valve. A minimal initial level of 5cmH20 of PEEP was recommended for the first hour of the CPAP, with subsequent increments (up to 15cmH20) until a clinical improvement was obtained. CPAP was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Continuous Positive Airway Pressure: In arm description</description>
          </group>
        </group_list>
        <measure>
          <title>Intensive Care Unit Mortality</title>
          <description>Mortality (%) at Intensive Care Unit</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>28th Day Mortality</title>
        <description>Mortility of patients within of the first 28 days after randomization (either at intensive car unit or at hospital)</description>
        <time_frame>Mortality within 28 days of randomization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Non-Invasive Ventilation (NIV Group)</title>
            <description>For the Non-Invasive ventilation group, a BiPAP Vision was used, by setting the Inspiratory Positive Airway Pressure (IPAP) at a level that was required to achieve a tidal volume of approximately 8-10 ml/kg. Also an Expiratory Positive Airway Pressure (EPAP) was set at a minimum of 5 cmH20 during the first hour, gradually increasing until there was a clinical improvement. Fraction inspiratory of oxygen (FiO2) was applied to maintain a transcutaneous arterial oxygen saturation (SaO2) of 92%-94%. NIV was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Non-Invasive Ventilation: In arm description</description>
          </group>
          <group group_id="O2">
            <title>Continuous Positive Airway Pressure (CPAP) Group</title>
            <description>The Continuous Positive Airway Pressure was applied by using a flow generator that was capable of delivering a flow of 140 Liter/minute, with adjustable fractional inspired oxygen that ranged from 0.3 to 1.0. This was connected to the Positive End-Expiratory Pressure valve that was placed in the face mask. In the second instance, the CPAP system that was used was a Boussignac CPAP System. The Boussignac valve takes gas from a single source and splits it in order to create four high flow jets. These jets converge in the chamber creating a turbulence which creates a virtual valve. A minimal initial level of 5cmH20 of PEEP was recommended for the first hour of the CPAP, with subsequent increments (up to 15cmH20) until a clinical improvement was obtained. CPAP was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Continuous Positive Airway Pressure: In arm description</description>
          </group>
        </group_list>
        <measure>
          <title>28th Day Mortality</title>
          <description>Mortility of patients within of the first 28 days after randomization (either at intensive car unit or at hospital)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hospital Mortality</title>
        <description>Mortality during hospital stay (including at Intensive care mortality)</description>
        <time_frame>Mortality (%) at Hospital at discharge from hospital</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Non-Invasive Ventilation (NIV Group)</title>
            <description>For the Non-Invasive ventilation group, a BiPAP Vision was used, by setting the Inspiratory Positive Airway Pressure (IPAP) at a level that was required to achieve a tidal volume of approximately 8-10 ml/kg. Also an Expiratory Positive Airway Pressure (EPAP) was set at a minimum of 5 cmH20 during the first hour, gradually increasing until there was a clinical improvement. Fraction inspiratory of oxygen (FiO2) was applied to maintain a transcutaneous arterial oxygen saturation (SaO2) of 92%-94%. NIV was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Non-Invasive Ventilation: In arm description</description>
          </group>
          <group group_id="O2">
            <title>Continuous Positive Airway Pressure (CPAP) Group</title>
            <description>The Continuous Positive Airway Pressure was applied by using a flow generator that was capable of delivering a flow of 140 Liter/minute, with adjustable fractional inspired oxygen that ranged from 0.3 to 1.0. This was connected to the Positive End-Expiratory Pressure valve that was placed in the face mask. In the second instance, the CPAP system that was used was a Boussignac CPAP System. The Boussignac valve takes gas from a single source and splits it in order to create four high flow jets. These jets converge in the chamber creating a turbulence which creates a virtual valve. A minimal initial level of 5cmH20 of PEEP was recommended for the first hour of the CPAP, with subsequent increments (up to 15cmH20) until a clinical improvement was obtained. CPAP was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Continuous Positive Airway Pressure: In arm description</description>
          </group>
        </group_list>
        <measure>
          <title>Hospital Mortality</title>
          <description>Mortality during hospital stay (including at Intensive care mortality)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <desc>Serious and Other Adverse Events were not assessed.</desc>
      <group_list>
        <group group_id="E1">
          <title>Non-Invasive Ventilation (NIV Group)</title>
          <description>For the NIV group, a BiPAP Vision was used, by setting the Inspiratory Positive Airway Pressure (IPAP) at a level that was required to achieve a tidal volume of approximately 8-10 ml/kg. Also an Expiratory Positive Airway Pressure (EPAP) was set at a minimum of 5 cmH20 during the first hour, gradually increasing until there was a clinical improvement. Fraction inspiratory of oxygen (FiO2) was applied to maintain a transcutaneous arterial oxygen saturation (SaO2) of 92%-94%. NIV was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Non-Invasive Ventilation: In arm description</description>
        </group>
        <group group_id="E2">
          <title>Continuous Positive Airway Pressure (CPAP) Group</title>
          <description>The CPAP was applied by using a flow generator that was capable of delivering a flow of 140 Liter /minute, with adjustable fractional inspired oxygen (FiO2) that ranged from 0.3 to 1.0. This was connected to the Positive End-Expiratory Pressure (PEEP) valve that was placed in the face mask. In the second instance, the CPAP system that was used was a Boussignac CPAP System Flow Jet. The Boussignac valve takes gas from a single source and splits it in order to create four high flow jets. These jets converge in the chamber creating a turbulence which creates a virtual valve. A minimal initial level of 5cmH20 of PEEP was recommended for the first hour of the CPAP, with subsequent increments (up to 15cmH20) until a clinical improvement was obtained. CPAP was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.&#xD;
Continuous Positive Airway Pressure: In arm description</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="56"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Alberto Belenguer Muncharaz</name_or_title>
      <organization>INTENSIVE CARE UNIT. HOSPITAL GENERAL UNIVERSITARI CASTELLO</organization>
      <phone>0034-964-725000</phone>
      <email>belengueralberto8@gmail.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02977572
org study id: HGU Castellon-002
nct id: NCT02977572
lead sponsor: 
has dmc: No
The aim of the present study was to demonstrate that an Non-Invasive Ventilation (NIV)
      performs better than a Continuous Positive Airway Pressure (CPAP) in the management of
      Cardiogenic Pulmonary Edema (CPE) within an Intensive Care Unit (ICU) setting.
Continuous Positive Airway Pressure (CPAP) and Non-Invasive Ventilation (NIV), has played a
      decisive role in the treatment of Acute Respiratory Failure (ARF) secondary to Cardiogenic
      Pulmonary Edema (CPE). The use of either CPAP or NIV has resulted in greater clinical
      improvements than the ones that have been previously obtained by using a standard medical
      therapy. Although there is a strong indication for NIV in hypercapnic patients, the situation
      whether NIV is superior to CPAP remains unclear, and hence, both have been recommended.

      NIV and CPAP have both been successfully used in patients admitted to an Intensive Care Unit
      (ICU) suffering from CPE. However, few trials have been published on the ICU scenario. In
      addition, Acute Coronary Syndrome (ACS) has been considered to be an exclusion criterion in
      several trials.

      At the time of the onset of CPE, either in the Emergency Department (ED) or in the ward, all
      participants received a standard medical therapy (oxygen through a Venturi mask, morphine,
      intravenous nitroglycerin if their systolic blood pressure >160 mmHg, together with loop
      diuretics), all at the discretion of the attending physician. In the absence of a clinical
      improvement [dyspnea, respiratory rate >25rpm, transcutaneous arterial oxygen saturation
      (SaO2) <90%], the participant was admitted to the ICU and assigned to the NIV group or the
      CPAP group, regardless of the treatment that they had received in the ED. The participants
      that were admitted to the ICU at the onset of CPE were randomised without a trial of medical
      treatment. The assignment of each group was performed by opening a sealed envelope following
      a prior randomisation by using a computerised system.

      Statistical. A comparative analysis was conducted by using the Student's t-test or the
      Mann-Whitney test for a comparison of the quantitative variables for the parametric and
      non-parametric characteristics, respectively. For the qualitative variables, the
      investigators used the Chi-Square statistic or Fisher's exact test. A statistical
      significance was reached if P<0.05. The cumulative probability of survival was compared by
      using a Kaplan-Meier estimation of survival and a Log-Rank Test to compare both of the
      groups.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Need for an Endotracheal Intubation Within Seven Days After Onset of Cardiopulmonary Edema at the Intensive Care Unit
time frame: Whitin seven days after onset of cardiopulmonary edema at the Intensive Care Unit
measure: Duration of the Ventilation
time frame: Time (hours) from start of ventilation until the removal of both devices because of improve or failure
description: Period of ventilation (either noninvasive ventilation or continouos positive airway pressure) while the patient suffers from acute respiratory failure secondary to cardiopulmonary edema
measure: Ventilator Acquired Pneumonia
time frame: Pulmonary infection at intensive care unit diagnosed until 72 hours after removal of ventilation
description: Pulmonary infections (%) during stay at intensive care unit
measure: Acute Renal Failure
time frame: Acute Renal Failure during intensive care unit stay (at discharge from intensive care unit)
description: Development of acute renal failure measured as increase of level of creatinine
measure: Length of Stay at Intensive Care Unit
time frame: Length of stay (days) at Intensive Care Unit at discharge from intensive care unit.
description: Length of stay of the patient at Intensive Care Unit
measure: Length of Hospital Stay
time frame: Length of stay (days) at hospital at discharge from hospital
description: All the time (days) the patient stays at the hospital
measure: Intensive Care Unit Mortality
time frame: Mortality (%) at Intensive Care Unit at discharge from intensive care unit
description: Mortality (%) at Intensive Care Unit
measure: 28th Day Mortality
time frame: Mortality within 28 days of randomization
description: Mortility of patients within of the first 28 days after randomization (either at intensive car unit or at hospital)
measure: Hospital Mortality
time frame: Mortality (%) at Hospital at discharge from hospital
description: Mortality during hospital stay (including at Intensive care mortality)
arm group label: Non-Invasive ventilation (NIV group)
arm group type: Experimental
description: For the NIV group, a BiPAP Vision was used, by setting the Inspiratory Positive Airway Pressure (IPAP) at a level that was required to achieve a tidal volume of approximately 8-10 ml/kg. Also an Expiratory Positive Airway Pressure (EPAP) was set at a minimum of 5 cmH20 during the first hour, gradually increasing until there was a clinical improvement. Fraction inspiratory of oxygen (FiO2) was applied to maintain a transcutaneous arterial oxygen saturation (SaO2) of 92%-94%. NIV was continuously applied until there was a clinical and/or a gasometrical improvement, at which time they were replaced by a Venturi mask with FiO2 of 0.4.
arm group label: Continuous Positive AirwayPressure CPAP
arm group type: Placebo Comparator
description: The CPAP was applied by using a flow generator with adjustable fractional inspired oxygen (FiO2). This was connected to the Positive End-Expiratory Pressure (PEEP) valve that was placed in the face mask. In the second instance, the CPAP system that was used was a Boussignac CPAP System Flow Jet. The Boussignac valve takes gas from a single source and splits it in order to create four high flow jets. These jets converge in the chamber creating a virtual valve. A initial level of 5cmH20 of PEEP was recommended for the first hour of ventilation, with subsequent increments (up to 15cmH20) until a clinical improvement was obtained. CPAP was continuously applied until there was a clinical and/or a gasometrical improvement, at which time it was replaced by a Venturi mask.
intervention type: Device
intervention name: Non-Invasive Ventilation
description: In arm description
arm group label: Non-Invasive ventilation (NIV group)
intervention type: Device
intervention name: Continuous Positive AirwayPressure CPAP
description: In arm description
arm group label: Continuous Positive AirwayPressure CPAP
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: ALBERTO BELENGUER-MUNCHARAZ, MD
role: Principal Investigator
affiliation: INTENSIVE CARE UNIT. HOSPITAL GENERAL CASTELLO
responsible party type: Principal Investigator
investigator affiliation: Hospital General Universitario de Castellón
investigator full name: ALBERTO BELENGUER MUNCHARAZ
investigator title: MD, Phd, INTENSIVE CARE UNIT
mesh term: Pulmonary Edema
mesh term: Edema
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 