<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/NCT04401150</url>
  </required_header>
  <id_info>
    <org_study_id>MP-31-2021-3741</org_study_id>
    <nct_id>NCT04401150</nct_id>
  </id_info>
  <brief_title>Lessening Organ Dysfunction With VITamin C - COVID-19</brief_title>
  <acronym>LOVIT-COVID</acronym>
  <official_title>Lessening Organ Dysfunction With VITamin C - COVID</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Université de Sherbrooke</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Lotte &amp; John Hecht Memorial Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Université de Sherbrooke</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>
      LOVIT-COVID is a multicentre concealed-allocation parallel-group blinded randomized&#xD;
      controlled trial to ascertain the effect of high-dose intravenous vitamin C compared to&#xD;
      placebo on mortality or persistent organ dysfunction at 28 days in hospitalized COVID-19&#xD;
      patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background. Research suggests that vitamin C is potentially lifesaving in the intense&#xD;
      inflammatory cascade such as that associated with COVID-19. Inflammation and oxidative stress&#xD;
      are among the main mechanisms underlying COVID-19-associated acute hypoxemic respiratory&#xD;
      failure. Previous evidence had also already established that a dysregulated inflammatory&#xD;
      cascade may distinguish patients who transition from a relatively mild viral pneumonitis to&#xD;
      acute respiratory distress syndrome and multiorgan failure. As such, adjunct immune&#xD;
      modulation therapies may improve outcomes of COVID-19 patients who are hospitalized. Numerous&#xD;
      preclinical studies have shown that, in addition to direct scavenging of oxygen radicals,&#xD;
      vitamin C limits their production and restores endothelial function.&#xD;
&#xD;
      As the majority of hospitalized patients with COVID-19 are not critically ill, avoiding&#xD;
      clinical deterioration and subsequent intensive care unit admission is a high priority.&#xD;
      Participation in research should be offered before patients become critically ill, at which&#xD;
      time many perceive that treatment may be too late. It is important to ensure that as many&#xD;
      COVID-19 patients as possible are offered the opportunity to participate to research since&#xD;
      that is generally the only means to access investigational therapies. The proposed trial will&#xD;
      address this gap, by evaluating the efficacy of intravenous vitamin C in hospitalized&#xD;
      patients with confirmed COVID-19.&#xD;
&#xD;
      Objectives. The overarching objective, which is identical to the objective of the parent&#xD;
      LOVIT trial (NCT 03680274), is to determine whether intravenous vitamin C, compared to&#xD;
      placebo, reduces morbidity and mortality in patients hospitalized with COVID-19. To ascertain&#xD;
      the volume of distribution, clearance, and plasma concentration over a course of 96 hours of&#xD;
      intravenous vitamin C 50 mg/kg of weight every 6 hours or matching placebo (pharmacokinetic&#xD;
      (PK) substudy).&#xD;
&#xD;
      Methods. Patients will be randomly assigned to vitamin C (intravenous, 50 mg/kg every 6h) or&#xD;
      placebo (0.9% NaCl or dextrose 5% in water) for 96 hours. Study personnel at the clinical&#xD;
      sites will document the composite of death or persistent organ dysfunction at day 28. Daily&#xD;
      assessments will occur for organ function, on days 1, 3, 7 for inflammation, infection, and&#xD;
      endothelial injury biomarkers, at baseline for vitamin C level, and at 6 months for mortality&#xD;
      and HRQoL. The LOVIT-COVID Trial will be conducted in Canadian and possibly international&#xD;
      sites. For the PK substudy: Blood samples will be drawn around the 8th dose at time 0 and&#xD;
      then after administration at times 1h, 2h, 4h and 6h (the 6h level will be immediately prior&#xD;
      to the next dose). The PK substudy will be conducted with 100 participants in some of the&#xD;
      participating centers.&#xD;
&#xD;
      Relevance. A growing body of evidence suggests that vitamin C, an inexpensive and readily&#xD;
      available intervention, is potentially lifesaving in sepsis and may also be beneficial in&#xD;
      COVID-19. LOVIT-COVID will constitute rigorous assessments of the effect of vitamin C&#xD;
      monotherapy on patient-important outcomes. If proven effective, vitamin C could be used&#xD;
      worldwide and drastically change outcomes in high- and low-income settings alike.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 14, 2020</start_date>
  <completion_date type="Actual">December 6, 2022</completion_date>
  <primary_completion_date type="Actual">July 15, 2022</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>
    <intervention_model_description>Randomized controlled trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Only the pharmacist of the participating site will be unblinded for the preparation of the study drug to be administered.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Death or persistent organ dysfunction</measure>
    <time_frame>Both assessed at 28 days</time_frame>
    <description>Number of deceased participants or with persistant organ dysfunction (dependency on mechanical ventilation, new renal replacement therapy, or vasopressors).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of intensive care unit-free days</measure>
    <time_frame>Assessed at 21 days</time_frame>
    <description>Number of whole and part study days for which the patient is alive and not admitted to an intensive care unit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Persistent organ dysfunction-free days in ICU</measure>
    <time_frame>Assessed at 28 days</time_frame>
    <description>Number of study days in ICU without persistant organ dysfunction</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients deceased at 6 months</measure>
    <time_frame>6 months</time_frame>
    <description>Mortality at 6 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health related quality of life in 6-month survivors</measure>
    <time_frame>6 months</time_frame>
    <description>Assessed by the EQ-5D-5L EuroQol questionnaire (EQ-5D-5L). The EQ-5D-5L essentially consists of 2 pages: the EQ-5D descriptive system and the EQ-5D visual analog scale (EQ VAS). The descriptive system comprises 5 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 her/his health state by ticking the box next to the most appropriate statement in each of the 5 dimension. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the 5 dimensions can be combined into a 5-digit number that describes the patient's health state.&#xD;
The EQ-VAS records the patient's self-rated health on a vertical visual analog scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Organ function</measure>
    <time_frame>Days 1, 2, 3, 4, 7, 10, 14, 28</time_frame>
    <description>Assessed by the Sequential Organ Failure Assessment (SOFA) score. Used to track a person's status during the stay in an intensive care unit to determine the extent of a person's organ function or rate of failure. The score is based on six different sub-scores, one each for the respiratory (PaO2/fraction of inspired oxygen FiO2) mmHg), cardiovascular (mean arterial pressure OR administration of vasopressors required), hepatic (liver bilirubin mg/dl [µmol/L]), coagulation (platelets x 103/µl), renal (kidneys creatinine (mg/dl) [µmol/L] (or urine output)), and neurological (Glasgow coma scale). The sub-score of each system ranges from 0 (best) to +4 (worst).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global tissue dysoxia</measure>
    <time_frame>Days 1, 3, 7</time_frame>
    <description>Assessed by serum lactate concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of inflammation</measure>
    <time_frame>Days 1, 3, 7</time_frame>
    <description>Assessed by interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of infection</measure>
    <time_frame>Days 1, 3, 7</time_frame>
    <description>Assessed by procalcitonin (PCT).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of endothelial injury</measure>
    <time_frame>Days 1, 3, 7</time_frame>
    <description>Assessed by thrombomodulin (TM) and angiopoietin-2 (ANG-2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of stage 3 acute kidney injury</measure>
    <time_frame>Up to day 28</time_frame>
    <description>Assessed by Kidney Disease: Improving Global Outcomes (KDIGO) criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute hemolysis</measure>
    <time_frame>Up to day 28</time_frame>
    <description>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;
lactate dehydrogenase (LDH) &gt;2 times upper limit of normal at clinical site lab.&#xD;
Severe hemolysis:&#xD;
o 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>Core lab-validated glucose level &lt;3.8 mmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vitamin C volume of distribution</measure>
    <time_frame>8th dose of vitamin C at time 0 (immediately prior to the dose) and then after administration at times 1 hour, 2 hours, 4 hours and 6 hours (Pharmacokynetic substudy).</time_frame>
    <description>Assessed by chromatography-tandem mass spectrometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vitamin C clearance</measure>
    <time_frame>8th dose of vitamin C at time 0 (immediately prior to the dose) and then after administration at times 1 hour, 2 hours, 4 hours and 6 hours (Pharmacokynetic substudy).</time_frame>
    <description>Assessed by chromatography-tandem mass spectrometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vitamin C plasma concentration</measure>
    <time_frame>8th dose of vitamin C at time 0 (immediately prior to the dose) and then after administration at times 1 hour, 2 hours, 4 hours and 6 hours (Pharmacokynetic substudy).</time_frame>
    <description>Assessed by chromatography-tandem mass spectrometry</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">392</enrollment>
  <condition>Vitamin C</condition>
  <condition>COVID-19</condition>
  <condition>Hospitalized Patients</condition>
  <arm_group>
    <arm_group_label>Vitamin C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vitamin C: 50 mg/kg of weight administered intravenously every 6 hours for 96 hours (16 doses).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Normal saline (0.9% NaCl) or dextrose 5% in water (D5W) in a volume to match the vitamin C.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin C</intervention_name>
    <description>Intravenous vitamin C administered in bolus doses of 50 mg/kg mixed in a 50-ml solution of either normal saline (0.9% NaCl) or dextrose 5% in water (D5W) during 30 to 60 minutes, every 6 hours for 96 hours (i.e. 200 mg/kg/day and 16 doses in total).</description>
    <arm_group_label>Vitamin C</arm_group_label>
    <other_name>Ascorbic acid</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Control</intervention_name>
    <description>Dextrose 5% in water of normal saline (0.9% NaCL) in a volume to match vitamin C.</description>
    <arm_group_label>Control</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed diagnosis of COVID-19;&#xD;
&#xD;
          -  Admitted to hospital (ward or intensive care unit).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Receiving or has received vasopressors during the current hospitalization;&#xD;
&#xD;
          -  More than 24 hours has elapsed since receipt of non-invasive ventilatory support&#xD;
             (high-flow nasal cannula or continuous positive airway pressure or non-invasive&#xD;
             ventilation) or invasive mechanical ventilation;&#xD;
&#xD;
          -  Patient is expected to be discharged from the hospital in the next 24 hours;&#xD;
&#xD;
          -  More than 14 days have elapsed since the commencement of hospital admission with&#xD;
             respiratory illness;&#xD;
&#xD;
          -  Known glucose-6-phosphate dehydrogenase (G6PD) deficiency;&#xD;
&#xD;
          -  Known sickle cell anemia&#xD;
&#xD;
          -  Pregnancy or breastfeeding;&#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;
&#xD;
        The trial has broad eligibility criteria and includes all COVID-19 patients admitted to the&#xD;
        hospital (e.g. hospital ward or the intensive care unit) who are not receiving&#xD;
        vasopressors.&#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>François Lamontagne, MD, FRCPC, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Université de Sherbrooke and CIUSSS de l'Estrie - CHUS</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Neill K Adhikari, MDCM, FRCPC, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sunnybrook Health Sciences Centre, University of Toronto</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Center of the CHUS</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <zip>J1H 5N4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Centre of the CHUS</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <zip>J1H 5N4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>May 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <last_update_submitted>April 20, 2023</last_update_submitted>
  <last_update_submitted_qc>April 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Université de Sherbrooke</investigator_affiliation>
    <investigator_full_name>François Lamontagne</investigator_full_name>
    <investigator_title>Co-Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Vitamin C</keyword>
  <keyword>COVID-19</keyword>
  <keyword>Hospitalized patients</keyword>
  <keyword>Pandemic</keyword>
  <keyword>Coronavirus</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</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>Undecided</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/NCT04401150
org study id: MP-31-2021-3741
nct id: NCT04401150
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
LOVIT-COVID is 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 hospitalized COVID-19
      patients.
Background. Research suggests that vitamin C is potentially lifesaving in the intense
      inflammatory cascade such as that associated with COVID-19. Inflammation and oxidative stress
      are among the main mechanisms underlying COVID-19-associated acute hypoxemic respiratory
      failure. Previous evidence had also already established that a dysregulated inflammatory
      cascade may distinguish patients who transition from a relatively mild viral pneumonitis to
      acute respiratory distress syndrome and multiorgan failure. As such, adjunct immune
      modulation therapies may improve outcomes of COVID-19 patients who are hospitalized. Numerous
      preclinical studies have shown that, in addition to direct scavenging of oxygen radicals,
      vitamin C limits their production and restores endothelial function.

      As the majority of hospitalized patients with COVID-19 are not critically ill, avoiding
      clinical deterioration and subsequent intensive care unit admission is a high priority.
      Participation in research should be offered before patients become critically ill, at which
      time many perceive that treatment may be too late. It is important to ensure that as many
      COVID-19 patients as possible are offered the opportunity to participate to research since
      that is generally the only means to access investigational therapies. The proposed trial will
      address this gap, by evaluating the efficacy of intravenous vitamin C in hospitalized
      patients with confirmed COVID-19.

      Objectives. The overarching objective, which is identical to the objective of the parent
      LOVIT trial (NCT 03680274), is to determine whether intravenous vitamin C, compared to
      placebo, reduces morbidity and mortality in patients hospitalized with COVID-19. To ascertain
      the volume of distribution, clearance, and plasma concentration over a course of 96 hours of
      intravenous vitamin C 50 mg/kg of weight every 6 hours or matching placebo (pharmacokinetic
      (PK) substudy).

      Methods. Patients will be randomly assigned to vitamin C (intravenous, 50 mg/kg every 6h) or
      placebo (0.9% NaCl or dextrose 5% in water) for 96 hours. Study personnel at the clinical
      sites will document the composite of death or persistent organ dysfunction at day 28. Daily
      assessments will occur for organ function, on days 1, 3, 7 for inflammation, infection, and
      endothelial injury biomarkers, at baseline for vitamin C level, and at 6 months for mortality
      and HRQoL. The LOVIT-COVID Trial will be conducted in Canadian and possibly international
      sites. For the PK substudy: Blood samples will be drawn around the 8th dose at time 0 and
      then after administration at times 1h, 2h, 4h and 6h (the 6h level will be immediately prior
      to the next dose). The PK substudy will be conducted with 100 participants in some of the
      participating centers.

      Relevance. A growing body of evidence suggests that vitamin C, an inexpensive and readily
      available intervention, is potentially lifesaving in sepsis and may also be beneficial in
      COVID-19. LOVIT-COVID will constitute rigorous assessments of the effect of vitamin C
      monotherapy on patient-important outcomes. If proven effective, vitamin C could be used
      worldwide and drastically change outcomes in high- and low-income settings alike.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized controlled trial
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Only the pharmacist of the participating site will be unblinded for the preparation of the study drug to be administered.
measure: Death or persistent organ dysfunction
time frame: Both assessed at 28 days
description: Number of deceased participants or with persistant organ dysfunction (dependency on mechanical ventilation, new renal replacement therapy, or vasopressors).
measure: Number of intensive care unit-free days
time frame: Assessed at 21 days
description: Number of whole and part study days for which the patient is alive and not admitted to an intensive care unit
measure: Persistent organ dysfunction-free days in ICU
time frame: Assessed at 28 days
description: Number of study days in ICU without persistant organ dysfunction
measure: Number of patients deceased at 6 months
time frame: 6 months
description: Mortality at 6 months
measure: Health related quality of life in 6-month survivors
time frame: 6 months
description: Assessed by the EQ-5D-5L EuroQol questionnaire (EQ-5D-5L). The EQ-5D-5L essentially consists of 2 pages: the EQ-5D descriptive system and the EQ-5D visual analog scale (EQ VAS). The descriptive system comprises 5 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 her/his health state by ticking the box next to the most appropriate statement in each of the 5 dimension. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the 5 dimensions can be combined into a 5-digit number that describes the patient's health state.
The EQ-VAS records the patient's self-rated health on a vertical visual analog scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'.
measure: Organ function
time frame: Days 1, 2, 3, 4, 7, 10, 14, 28
description: Assessed by the Sequential Organ Failure Assessment (SOFA) score. Used to track a person's status during the stay in an intensive care unit to determine the extent of a person's organ function or rate of failure. The score is based on six different sub-scores, one each for the respiratory (PaO2/fraction of inspired oxygen FiO2) mmHg), cardiovascular (mean arterial pressure OR administration of vasopressors required), hepatic (liver bilirubin mg/dl [µmol/L]), coagulation (platelets x 103/µl), renal (kidneys creatinine (mg/dl) [µmol/L] (or urine output)), and neurological (Glasgow coma scale). The sub-score of each system ranges from 0 (best) to +4 (worst).
measure: Global tissue dysoxia
time frame: Days 1, 3, 7
description: Assessed by serum lactate concentration
measure: Rate of inflammation
time frame: Days 1, 3, 7
description: Assessed by interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP).
measure: Rate of infection
time frame: Days 1, 3, 7
description: Assessed by procalcitonin (PCT).
measure: Rate of endothelial injury
time frame: Days 1, 3, 7
description: Assessed by thrombomodulin (TM) and angiopoietin-2 (ANG-2).
measure: Occurrence of stage 3 acute kidney injury
time frame: Up to day 28
description: Assessed by Kidney Disease: Improving Global Outcomes (KDIGO) criteria
measure: Acute hemolysis
time frame: Up to day 28
description: 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:
o 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: Core lab-validated glucose level <3.8 mmol/L
measure: Vitamin C volume of distribution
time frame: 8th dose of vitamin C at time 0 (immediately prior to the dose) and then after administration at times 1 hour, 2 hours, 4 hours and 6 hours (Pharmacokynetic substudy).
description: Assessed by chromatography-tandem mass spectrometry
measure: Vitamin C clearance
time frame: 8th dose of vitamin C at time 0 (immediately prior to the dose) and then after administration at times 1 hour, 2 hours, 4 hours and 6 hours (Pharmacokynetic substudy).
description: Assessed by chromatography-tandem mass spectrometry
measure: Vitamin C plasma concentration
time frame: 8th dose of vitamin C at time 0 (immediately prior to the dose) and then after administration at times 1 hour, 2 hours, 4 hours and 6 hours (Pharmacokynetic substudy).
description: Assessed by chromatography-tandem mass spectrometry
arm group label: Vitamin C
arm group type: Experimental
description: Vitamin C: 50 mg/kg of weight administered intravenously every 6 hours for 96 hours (16 doses).
arm group label: Control
arm group type: Placebo Comparator
description: Normal saline (0.9% NaCl) or dextrose 5% in water (D5W) in a volume to match the vitamin C.
intervention type: Drug
intervention name: Vitamin C
description: Intravenous vitamin C administered in bolus doses of 50 mg/kg mixed in a 50-ml solution of either normal saline (0.9% NaCl) or dextrose 5% in water (D5W) during 30 to 60 minutes, every 6 hours for 96 hours (i.e. 200 mg/kg/day and 16 doses in total).
arm group label: Vitamin C
other name: Ascorbic acid
intervention type: Drug
intervention name: Control
description: Dextrose 5% in water of normal saline (0.9% NaCL) in a volume to match vitamin C.
arm group label: Control
other name: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: François Lamontagne, MD, FRCPC, MSc
role: Principal Investigator
affiliation: Université de Sherbrooke and CIUSSS de l'Estrie - CHUS
last name: Neill K Adhikari, MDCM, FRCPC, MSc
role: Principal Investigator
affiliation: Sunnybrook Health Sciences Centre, University of Toronto
facility: 
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Université de Sherbrooke
investigator full name: François Lamontagne
investigator title: Co-Principal Investigator
mesh term: COVID-19
mesh term: Ascorbic Acid
sharing ipd: Undecided