<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/NCT04404387</url>
  </required_header>
  <id_info>
    <org_study_id>APHP200019</org_study_id>
    <secondary_id>2019-003350-80</secondary_id>
    <secondary_id>2020-003923-40</secondary_id>
    <nct_id>NCT04404387</nct_id>
  </id_info>
  <brief_title>Lessening Organ Dysfunction With VITamin C in Septic ARDS</brief_title>
  <acronym>LOVIT ARDS</acronym>
  <official_title>A Multicentre Concealed-Allocation Parallel-Group Blinded Randomized Controlled Trial to Ascertain the Effect of High-Dose Intravenous Vitamin C Compared to Placebo on Mortality or Persistent Organ Dysfunction at 28 Days in Septic Intensive Care Unit Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</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>
      The primary objective of the study aims to compare the effect of high-dose intravenous&#xD;
      vitamin C vs. placebo on a composite of death or persistent organ dysfunction - defined as&#xD;
      continued dependency on mechanical ventilation, new renal replacement therapy, or&#xD;
      vasopressors - assessed at 28 days on intensive care unit (ICU) patients.&#xD;
&#xD;
      As secondary objectives, the study aims:&#xD;
&#xD;
        -  To compare the effect of high-dose intravenous vitamin C vs. placebo on:&#xD;
&#xD;
             1. 6-month mortality;&#xD;
&#xD;
             2. 6-month HRQoL;&#xD;
&#xD;
             3. organ function (days 1, 2, 3, 4, 7, 10, 14, and 28 if in ICU);&#xD;
&#xD;
             4. global tissue dysoxia (at baseline);&#xD;
&#xD;
             5. oxygenation Index (FiO2 x Mean Airway Pressure/PaO2) (days 1, 2, 3, 4, 7, 10, 14,&#xD;
                and 28 if in ICU, and if still intubated);&#xD;
&#xD;
             6. occurrence of stage 3 acute kidney injury as defined by KDIGO (Kidney Disease:&#xD;
                Improving Global Outcomes) criteria20;&#xD;
&#xD;
             7. acute hemolysis as defined by:&#xD;
&#xD;
                  -  clinician judgment of hemolysis, as recorded in the chart, or&#xD;
&#xD;
                  -  hemoglobin drop of at least 25 g/L within 24 hours of a dose of&#xD;
                     investigational product PLUS 2 of the following:&#xD;
&#xD;
                       -  reticulocyte count &gt;2 times upper limit of normal at clinical site lab;&#xD;
&#xD;
                       -  haptoglobin &lt; lower limit of normal at clinical site lab;&#xD;
&#xD;
                       -  indirect (unconjugated) bilirubin &gt;2 times upper limit of normal at&#xD;
                          clinical site lab;&#xD;
&#xD;
                       -  lactate dehydrogenase (LDH) &gt;2 times upper limit of normal at clinical&#xD;
                          site lab.&#xD;
&#xD;
                Severe hemolysis:&#xD;
&#xD;
                - hemoglobin &lt; 75 g/L AND at least 2 of the above criteria AND requires 2 units of&#xD;
                packed red blood cells;&#xD;
&#xD;
             8. hypoglycemia as defined as core lab-validated glucose levels of less than &lt; 3.8&#xD;
                mmol/L.&#xD;
&#xD;
        -  To assess baseline vitamin C levels in study participants (before the first dose of&#xD;
           investigational product).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Treatment options for sepsis complicated by ARDS are limited to antimicrobials and supportive&#xD;
      care (intravenous fluids, vasopressors, mechanical ventilation and renal replacement&#xD;
      therapy). Recent preliminary evidence suggests that intravenous vitamin C may be the first&#xD;
      therapy to mitigate the dysregulated cascade of events transforming an infection into sepsis.&#xD;
      However, definitive practice changing evidence requires a large trial powered to detect a&#xD;
      plausible, modest, and clinically important difference in mortality.&#xD;
&#xD;
      The study LOVIT will be conducted simultaneously in Canada (country of coordination), France,&#xD;
      the United States of America, the United Kingdom and Australia/New Zealand.The data from each&#xD;
      country will be merged with the aim of reaching 4,000 patients globally (roughly 800 patients&#xD;
      per country). Thus, in the context of increasing off-label use of vitamin C for sepsis and&#xD;
      ongoing trials of vitamin C bundled with other pharmacological interventions, this study will&#xD;
      constitute a rigorous assessment of the effect of vitamin C monotherapy on patient-important&#xD;
      outcomes. Moreover, the French LOVIT-ARDS, part of LOVIT, will provide additional information&#xD;
      on the specific subgroup of patients with sepsis and ARDS.&#xD;
&#xD;
      This is a prospective multicentric randomized controlled trial. Web-based randomization&#xD;
      system available 24/7. Eligible patients will be randomized in a 1:1 ratio to vitamin C or&#xD;
      matching placebo. The study will use permuted blocks of undisclosed and variable size and&#xD;
      stratify randomization by site.&#xD;
&#xD;
      The study will enroll a total of at least 770 patients. Sites are expected to enroll at least&#xD;
      1or 2 patients per month. By enrolling 385 evaluable patients per arm, the study will have&#xD;
      80% power to detect a 10% absolute risk reduction (from 50% to 40%, which corresponds to a&#xD;
      20% relative risk reduction).&#xD;
&#xD;
      Follow-up in the study for each patient: daily during ICU stay and telephone follow-up at 6&#xD;
      months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 22, 2022</start_date>
  <completion_date type="Anticipated">July 2024</completion_date>
  <primary_completion_date type="Anticipated">July 2024</primary_completion_date>
  <phase>Phase 3</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of deceased participants or with persistent organ dysfunction</measure>
    <time_frame>Both assessed at 28 days</time_frame>
    <description>Defined as death or persistent organ dysfunction: continued dependency on mechanical ventilation, renal replacement therapy, or vasopressors.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Vital statue at 6 months</measure>
    <time_frame>at 6 months</time_frame>
    <description>Mortality at 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life assessement: EQ-5D-5L</measure>
    <time_frame>at 6 months</time_frame>
    <description>Quality of life of patients will be assessed by the questionnaire EQ-5D-5L.&#xD;
The questionnaire EQ-5D-5L essentially consists of 2 pages:&#xD;
- page1: the EQ-5D-5L descriptive system:&#xD;
The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box (1-digit number) next to the most appropriate statement in each of the five dimensions.&#xD;
- page 2: the EQ visual analogue scale (VAS): the EQ VAS records the patient's self-rated health on a vertical visual analogue scale.&#xD;
The 2 parts of the questionnaire can not be assessed seperately.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Daily organ function</measure>
    <time_frame>Days 1, 2, 3, 4, 7, 10, 14, 28</time_frame>
    <description>Daily organ function (SOFA score days 1, 2, 3, 4, 7, 10, 14, and 28);</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global tissue dysoxia</measure>
    <time_frame>At baseline and days 1, 3, 7</time_frame>
    <description>Global tissue dysoxia: assessed by serum lactate concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of stage 3 acute kidney injury</measure>
    <time_frame>Up to day 28</time_frame>
    <description>Occurrence of stage 3 acute kidney injury as defined by KDIGO criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute hemolysis</measure>
    <time_frame>Up to day 28</time_frame>
    <description>Acute hemolysis as defined by:&#xD;
clinician judgment of hemolysis, as recorded in the chart, OR&#xD;
hemoglobin drop of at least 25 g/L within 24 hours of a dose of investigational product PLUS 2 of the following:&#xD;
reticulocyte count &gt;2 times upper limit of normal at clinical site lab;&#xD;
haptoglobin &lt; lower limit of normal at clinical site lab;&#xD;
indirect (unconjugated) bilirubin &gt;2 times upper limit of normal at clinical site lab;&#xD;
LDH &gt;2 times upper limit of normal at clinical site lab.&#xD;
Severe hemolysis:&#xD;
- hemoglobin &lt; 75 g/L AND at least 2 of the above criteria AND requires 2 units of packed red blood cells.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hypoglycemia</measure>
    <time_frame>During the time participants receive the 16 doses of the investigational product and the 7 days following the last dose</time_frame>
    <description>Hypoglycemia as defined by core lab-validated glucose levels of less than &lt; 3.8 mmol/L.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">800</enrollment>
  <condition>Septic</condition>
  <condition>Acute Respiratory Distress Syndrome</condition>
  <arm_group>
    <arm_group_label>Experimental arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>vitamin C 50 mg/kg every 6 hours for 96 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo administration</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Administration of vitamin C</intervention_name>
    <description>The intervention is intravenous vitamin C administered in bolus doses of 50 mg/kg mixed in a 50-mL solution of either dextrose 5% in water (D5W) or normal saline (0.9% NaCl), during 30 to 60 minutes or more for participants over 120 kg not to exceed 100 mg/minute, every 6 hours for 96 hours (i.e. 200 mg/kg/day and 16 doses in total).&#xD;
The other name of the drug: Ascorbic acid.</description>
    <arm_group_label>Experimental arm</arm_group_label>
    <other_name>Administration of Ascorbic acid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Administration of placebo</intervention_name>
    <description>Administration of placebo. Patients (in the control arm) will receive dextrose 5% in water (D5W) or normal saline (0.9% NaCl) in a volume to match the vitamin C. Placebo will be infused over 30 to 60 minutes or more for participants over 120 kg not to exceed 100 mg/minute as per the infusion instructions of vitamin C.</description>
    <arm_group_label>Control arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients ≥18 years;&#xD;
&#xD;
          -  Admitted to ICU with proven or suspected infection as the main diagnosis;&#xD;
&#xD;
          -  Currently treated with a continuous intravenous infusion of vasopressors&#xD;
             (norepinephrine, epinephrine, vasopressin, dopamine, phenylephrine);&#xD;
&#xD;
          -  Presenting with Acute Respiratory Distress Syndrome&#xD;
&#xD;
          -  Patient who has signed an informed and written consent, whenever he/she is capable of&#xD;
             consent, if not ascent from his/her representant whenever he/she is present at time of&#xD;
             screening for inclusion&#xD;
&#xD;
          -  Affiliation to a social security system or to an universal health coverage (Couverture&#xD;
             Maladie Universelle, CMU).&#xD;
&#xD;
          -  Patients under guardianship or curatorship will be included.&#xD;
&#xD;
          -  Patients in case of simple emergency (legal definition) will be included.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  &gt; 24 hours of intensive care unit (ICU) admission;&#xD;
&#xD;
          -  Known Glucose-6-phosphate dehydrogenase (G6PD) deficiency;&#xD;
&#xD;
          -  Pregnancy;&#xD;
&#xD;
          -  Known allergy to vitamin C;&#xD;
&#xD;
          -  Known kidney stones within the past 1 year;&#xD;
&#xD;
          -  Received any intravenous vitamin C during this hospitalization unless incorporated in&#xD;
             parenteral nutrition;&#xD;
&#xD;
          -  Expected death or withdrawal of life-sustaining treatments within 48 hours;&#xD;
&#xD;
          -  Previously enrolled in this study;&#xD;
&#xD;
          -  Previously enrolled in a trial for which co-enrolment is not allowed (co-enrolment to&#xD;
             be determined case by case).&#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>Djillali ANNANE, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department Intensive Care Unit, Hospital Raymond Poincaré - APHP</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Djillali ANNANE, MD, PhD</last_name>
    <phone>+33 1 47 10 77 87</phone>
    <email>djillali.annane@aphp.fr</email>
  </overall_contact>
  <location>
    <facility>
      <name>Department Intensive Care Unit, Hospital Raymond Poincaré - APHP</name>
      <address>
        <city>Garches</city>
        <zip>92100</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>May 19, 2020</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>October 10, 2022</last_update_submitted>
  <last_update_submitted_qc>October 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Septic</keyword>
  <keyword>Acute respiratory distress syndrome</keyword>
  <keyword>Vitamin C</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ascorbic Acid</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/NCT04404387
org study id: APHP200019
secondary id: 2019-003350-80
secondary id: 2020-003923-40
nct id: NCT04404387
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The primary objective of the study aims to compare the effect of high-dose intravenous
      vitamin C vs. placebo on a composite of death or persistent organ dysfunction - defined as
      continued dependency on mechanical ventilation, new renal replacement therapy, or
      vasopressors - assessed at 28 days on intensive care unit (ICU) patients.

      As secondary objectives, the study aims:

        -  To compare the effect of high-dose intravenous vitamin C vs. placebo on:

             1. 6-month mortality;

             2. 6-month HRQoL;

             3. organ function (days 1, 2, 3, 4, 7, 10, 14, and 28 if in ICU);

             4. global tissue dysoxia (at baseline);

             5. oxygenation Index (FiO2 x Mean Airway Pressure/PaO2) (days 1, 2, 3, 4, 7, 10, 14,
                and 28 if in ICU, and if still intubated);

             6. occurrence of stage 3 acute kidney injury as defined by KDIGO (Kidney Disease:
                Improving Global Outcomes) criteria20;

             7. acute hemolysis as defined by:

                  -  clinician judgment of hemolysis, as recorded in the chart, or

                  -  hemoglobin drop of at least 25 g/L within 24 hours of a dose of
                     investigational product PLUS 2 of the following:

                       -  reticulocyte count >2 times upper limit of normal at clinical site lab;

                       -  haptoglobin < lower limit of normal at clinical site lab;

                       -  indirect (unconjugated) bilirubin >2 times upper limit of normal at
                          clinical site lab;

                       -  lactate dehydrogenase (LDH) >2 times upper limit of normal at clinical
                          site lab.

                Severe hemolysis:

                - hemoglobin < 75 g/L AND at least 2 of the above criteria AND requires 2 units of
                packed red blood cells;

             8. hypoglycemia as defined as core lab-validated glucose levels of less than < 3.8
                mmol/L.

        -  To assess baseline vitamin C levels in study participants (before the first dose of
           investigational product).
Treatment options for sepsis complicated by ARDS are limited to antimicrobials and supportive
      care (intravenous fluids, vasopressors, mechanical ventilation and renal replacement
      therapy). Recent preliminary evidence suggests that intravenous vitamin C may be the first
      therapy to mitigate the dysregulated cascade of events transforming an infection into sepsis.
      However, definitive practice changing evidence requires a large trial powered to detect a
      plausible, modest, and clinically important difference in mortality.

      The study LOVIT will be conducted simultaneously in Canada (country of coordination), France,
      the United States of America, the United Kingdom and Australia/New Zealand.The data from each
      country will be merged with the aim of reaching 4,000 patients globally (roughly 800 patients
      per country). Thus, in the context of increasing off-label use of vitamin C for sepsis and
      ongoing trials of vitamin C bundled with other pharmacological interventions, this study will
      constitute a rigorous assessment of the effect of vitamin C monotherapy on patient-important
      outcomes. Moreover, the French LOVIT-ARDS, part of LOVIT, will provide additional information
      on the specific subgroup of patients with sepsis and ARDS.

      This is a prospective multicentric randomized controlled trial. Web-based randomization
      system available 24/7. Eligible patients will be randomized in a 1:1 ratio to vitamin C or
      matching placebo. The study will use permuted blocks of undisclosed and variable size and
      stratify randomization by site.

      The study will enroll a total of at least 770 patients. Sites are expected to enroll at least
      1or 2 patients per month. By enrolling 385 evaluable patients per arm, the study will have
      80% power to detect a 10% absolute risk reduction (from 50% to 40%, which corresponds to a
      20% relative risk reduction).

      Follow-up in the study for each patient: daily during ICU stay and telephone follow-up at 6
      months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of deceased participants or with persistent organ dysfunction
time frame: Both assessed at 28 days
description: Defined as death or persistent organ dysfunction: continued dependency on mechanical ventilation, renal replacement therapy, or vasopressors.
measure: Vital statue at 6 months
time frame: at 6 months
description: Mortality at 6 months
measure: Quality of life assessement: EQ-5D-5L
time frame: at 6 months
description: Quality of life of patients will be assessed by the questionnaire EQ-5D-5L.
The questionnaire EQ-5D-5L essentially consists of 2 pages:
- page1: the EQ-5D-5L descriptive system:
The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box (1-digit number) next to the most appropriate statement in each of the five dimensions.
- page 2: the EQ visual analogue scale (VAS): the EQ VAS records the patient's self-rated health on a vertical visual analogue scale.
The 2 parts of the questionnaire can not be assessed seperately.
measure: Daily organ function
time frame: Days 1, 2, 3, 4, 7, 10, 14, 28
description: Daily organ function (SOFA score days 1, 2, 3, 4, 7, 10, 14, and 28);
measure: Global tissue dysoxia
time frame: At baseline and days 1, 3, 7
description: Global tissue dysoxia: assessed by serum lactate concentration
measure: Occurrence of stage 3 acute kidney injury
time frame: Up to day 28
description: Occurrence of stage 3 acute kidney injury as defined by KDIGO criteria
measure: Acute hemolysis
time frame: Up to day 28
description: Acute hemolysis as defined by:
clinician judgment of hemolysis, as recorded in the chart, OR
hemoglobin drop of at least 25 g/L within 24 hours of a dose of investigational product PLUS 2 of the following:
reticulocyte count >2 times upper limit of normal at clinical site lab;
haptoglobin < lower limit of normal at clinical site lab;
indirect (unconjugated) bilirubin >2 times upper limit of normal at clinical site lab;
LDH >2 times upper limit of normal at clinical site lab.
Severe hemolysis:
- hemoglobin < 75 g/L AND at least 2 of the above criteria AND requires 2 units of packed red blood cells.
measure: Hypoglycemia
time frame: During the time participants receive the 16 doses of the investigational product and the 7 days following the last dose
description: Hypoglycemia as defined by core lab-validated glucose levels of less than < 3.8 mmol/L.
arm group label: Experimental arm
arm group type: Experimental
description: vitamin C 50 mg/kg every 6 hours for 96 hours.
arm group label: Control arm
arm group type: Placebo Comparator
description: Placebo administration
intervention type: Drug
intervention name: Administration of vitamin C
description: The intervention is intravenous vitamin C administered in bolus doses of 50 mg/kg mixed in a 50-mL solution of either dextrose 5% in water (D5W) or normal saline (0.9% NaCl), during 30 to 60 minutes or more for participants over 120 kg not to exceed 100 mg/minute, every 6 hours for 96 hours (i.e. 200 mg/kg/day and 16 doses in total).
The other name of the drug: Ascorbic acid.
arm group label: Experimental arm
other name: Administration of Ascorbic acid
intervention type: Drug
intervention name: Administration of placebo
description: Administration of placebo. Patients (in the control arm) will receive dextrose 5% in water (D5W) or normal saline (0.9% NaCl) in a volume to match the vitamin C. Placebo will be infused over 30 to 60 minutes or more for participants over 120 kg not to exceed 100 mg/minute as per the infusion instructions of vitamin C.
arm group label: Control arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Djillali ANNANE, MD, PhD
role: Principal Investigator
affiliation: Department Intensive Care Unit, Hospital Raymond Poincaré - APHP
last name: Djillali ANNANE, MD, PhD
phone: +33 1 47 10 77 87
email: djillali.annane@aphp.fr
facility: 
status: Recruiting
country: France
responsible party type: Sponsor
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury
mesh term: Ascorbic Acid
sharing ipd: No