<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/NCT03829683</url>
  </required_header>
  <id_info>
    <org_study_id>HM20014364</org_study_id>
    <secondary_id>U01AA026966</secondary_id>
    <nct_id>NCT03829683</nct_id>
  </id_info>
  <brief_title>Vitamin C Infusion for TReatment in Sepsis and Alcoholic Hepatitis</brief_title>
  <acronym>CITRIS-AH</acronym>
  <official_title>Vitamin C Infusion for TReatment in Sepsis and Alcoholic Hepatitis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Virginia Commonwealth University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Virginia Commonwealth University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research study is to test the safety, tolerability, and effectiveness of&#xD;
      Vitamin C (ascorbic acid) intravenous infusion when used to treat alcoholic hepatitis&#xD;
      (inflammation of the liver from heavy alcohol use) and sepsis (life-threatening complication&#xD;
      of an infection).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Alcoholic hepatitis is inflammation of the liver due to alcohol consumption. It can cause one&#xD;
      or more of the following symptoms such as jaundice (yellow discoloration of the eyes and&#xD;
      skin), pain on the right side of the abdomen, and is accompanied by an enlarged liver. Sepsis&#xD;
      is a life-threatening complication of an infection. As the body tries to fight an infection&#xD;
      it sends chemicals into the bloodstream. These chemicals that are trying to fight the&#xD;
      infection can cause inflammation. This inflammation can cause damage to many body systems and&#xD;
      make them fail. Patients with alcoholic hepatitis and sepsis have low levels of Vitamin C in&#xD;
      the bloodstream. Vitamin C has been shown to reduce inflammation and organ dysfunction in&#xD;
      patients with severe infections.&#xD;
&#xD;
      The investigators do not yet know if Vitamin C will be effective in alcoholic hepatitis.&#xD;
      Taking Vitamin C by mouth is not effective as a treatment in people with this condition so&#xD;
      participants will receive the Vitamin C intravenously (IV). Participants will be randomly&#xD;
      assigned to receive either Vitamin C or a placebo given through an IV every six hours for&#xD;
      four days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 16, 2019</start_date>
  <completion_date type="Actual">June 23, 2022</completion_date>
  <primary_completion_date type="Actual">March 31, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Study drug will be double-blind with matching placebo. Vitamin C 200mg/kg/24hours or placebo (Dextrose 5% in water) will be given intravenously every 6 hours for up to 96 hours of treatment.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Model for End Stage Liver Disease (MELD) Score</measure>
    <time_frame>Baseline and 96 hours</time_frame>
    <description>Change in MELD score from Day 0 to Day 4. MELD score ranges from 6 (least sick) to 40 (most sick) based on blood tests which ranks the degree of sickness from liver disease. The lab tests used to determine the MELD score are creatinine, bilirubin, and international normalized ratio (INR).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) Score</measure>
    <time_frame>Baseline and 96 hours</time_frame>
    <description>A number that ranges from 0 (least sick) to 24 (most sick) and ranks the degree of sickness from liver failure and several other organ systems in a critically ill person. The score is determined by evaluating a person's liver function, kidney function, nervous system (brain), coagulation (blood clotting), circulation (blood pressure), and respiratory status (breathing)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Aspartate Aminotransferase (AST) Level</measure>
    <time_frame>Baseline and 96 hours</time_frame>
    <description>Standard blood test used to determine the severity and nature of liver problems.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Alanine Aminotransferase (ALT) Level</measure>
    <time_frame>Baseline and 96 hours</time_frame>
    <description>Standard blood test used to determine the severity and nature of liver problems.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Total Bilirubin</measure>
    <time_frame>Baseline and 96 hours</time_frame>
    <description>Standard blood test used to determine the severity and nature of liver problems.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Alkaline Phosphatase</measure>
    <time_frame>Baseline and 96 hours</time_frame>
    <description>Standard blood test used to determine the severity and nature of liver problems.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Albumin</measure>
    <time_frame>Baseline and 96 hours</time_frame>
    <description>Standard blood test used to determine the severity and nature of liver problems.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Treatment-related Adverse Events as Assessed by CTCAE v5.0</measure>
    <time_frame>up to 96 hours</time_frame>
    <description>Observation about the need to change the dose of study medication and symptoms such as headache, dizziness, dry mouth, nausea, vomiting, flushing, rash, or hypotension (low blood pressure)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes to Corrected QT Interval (QTc)</measure>
    <time_frame>Baseline and 96 hours</time_frame>
    <description>An electrocardiogram (ECG or test of the electrical activity of the heart) is performed to determine if there are changes to the heart rhythm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes to Urine pH</measure>
    <time_frame>Baseline and 96 hours</time_frame>
    <description>Urine samples are collected to determine changes in pH (acidity) that could indicate a risk for kidney stones. The pH scale ranges from 0 to 14, with smaller numbers meaning more acidic and higher numbers meaning more basic. A pH of 7 is considered to be neutral. Normal levels of urine pH range from 4.6 - 8 on the pH scale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes to Urine Microscopy</measure>
    <time_frame>Baseline and 96 hours</time_frame>
    <description>Urine samples are collected to check for the presence of crystalluria (microscopic crystals) that could indicate a risk for kidney stones.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes to Level of Medical Care</measure>
    <time_frame>up to 168 hours</time_frame>
    <description>Documentation of the need for more intensive medical care such as ventilator (breathing machine) or vasopressors (intravenous medications use increase blood pressure) when not needed at baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU-free Days</measure>
    <time_frame>Day 28</time_frame>
    <description>The number of days not spent in an intensive care unit (ICU)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Deaths Due to Any Cause</measure>
    <time_frame>Day 28</time_frame>
    <description>Any cause of death that is anticipated or unanticipated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Deaths Due to Any Cause</measure>
    <time_frame>Day 90</time_frame>
    <description>Any cause of death that is anticipated or unanticipated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital-free Days</measure>
    <time_frame>Day 90</time_frame>
    <description>The number of days spent outside of the hospital</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Alcoholic Hepatitis</condition>
  <condition>Sepsis</condition>
  <arm_group>
    <arm_group_label>Vitamin C infusion (ascorbic acid)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin C</intervention_name>
    <description>200mg/kg/24hours</description>
    <arm_group_label>Vitamin C infusion (ascorbic acid)</arm_group_label>
    <other_name>ascorbic acid</other_name>
    <other_name>AscA</other_name>
    <other_name>Ascor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dextrose 5% in water</intervention_name>
    <description>50mL intravenously every 6 hours</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Vitamin C infusion (ascorbic acid)</arm_group_label>
    <other_name>D5W</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Alcoholic Hepatitis diagnosed by one of the following methods:&#xD;
&#xD;
               1. liver biopsy&#xD;
&#xD;
               2. clinical diagnosis based on history of alcohol use, presence of jaundice&#xD;
                  (yellowing of skin), blood tests indicating liver injury, and absence of other&#xD;
                  causes of liver injury (autoimmune disease, viral hepatitis, drug toxicity)&#xD;
&#xD;
          2. Suspected or proven infection&#xD;
&#xD;
          3. Presence of systemic inflammatory response to infection (fever, hypothermia (low&#xD;
             temperature), tachycardia (fast heart rate), leukocytosis (high white blood cell&#xD;
             count), leukopenia (low white blood cell count), high respiratory (breathing) rate, or&#xD;
             need for mechanical ventilation (a machine to assist in breathing).&#xD;
&#xD;
          4. Presence of organ failure due to the body's response to infection indicated by any of&#xD;
             the following:&#xD;
&#xD;
               1. Hypotension (low blood pressure) or need for medications to raise blood pressure&#xD;
&#xD;
               2. Arterial hypoxemia (low blood oxygen) or need for high flow of oxygen&#xD;
&#xD;
               3. High lactate level (blood test indicating active response to infection)&#xD;
&#xD;
               4. Low urine output despite administration of intravenous fluids&#xD;
&#xD;
               5. Low platelet count (blood test)&#xD;
&#xD;
               6. Coagulopathy (decreased blood clotting ability based on a blood test)&#xD;
&#xD;
               7. High bilirubin (blood test)&#xD;
&#xD;
               8. Mental status changes (confusion or delirium)&#xD;
&#xD;
          5. Absence of drugs present on urine or blood tests that indicate the possibility of&#xD;
             liver damage or mental status changes from other causes&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Allergy to Vitamin C&#xD;
&#xD;
          2. Unable to provide consent&#xD;
&#xD;
          3. Age less than 18 years&#xD;
&#xD;
          4. No intravenous access (IV line) in a patient needing glucose (blood sugar) checks more&#xD;
             than twice daily&#xD;
&#xD;
          5. Presence of diabetic ketoacidosis (a serious complication of diabetes)&#xD;
&#xD;
          6. Inability of patient, legally authorized representative and/or physician to commit to&#xD;
             full medical support&#xD;
&#xD;
          7. Pregnancy or breast feeding&#xD;
&#xD;
          8. Life expectancy less than 24 hours&#xD;
&#xD;
          9. Active or history of kidney stone&#xD;
&#xD;
         10. History of chronic kidney disease&#xD;
&#xD;
         11. History of glucose-6-phosphate deficiency (a low blood protein that can cause red&#xD;
             blood cells to break down)&#xD;
&#xD;
         12. Active cancer (except non-melanoma skin cancer)&#xD;
&#xD;
         13. Uncontrolled gastrointestinal bleeding&#xD;
&#xD;
         14. Other causes of liver injury such as viruses, autoimmune disease, drug toxicity&#xD;
&#xD;
         15. History of severe liver cirrhosis complications including variceal bleeding within the&#xD;
             last 3 months, large ascites (fluid accumulation in the abdomen) or hepatocellular&#xD;
             carcinoma (liver cancer)&#xD;
&#xD;
         16. History of organ transplantation&#xD;
&#xD;
         17. Initial AST or ALT (blood test indicating a liver problem)&#xD;
&#xD;
         18. Presence of acetaminophen or other drugs on urine or blood toxicology test&#xD;
&#xD;
         19. Non-English speaking&#xD;
&#xD;
         20. Prisoner or other ward of the state&#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>Arun J Sanyal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Virginia Commonwealth University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Virginia Commonwealth University</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>January 17, 2019</study_first_submitted>
  <study_first_submitted_qc>February 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <results_first_submitted>February 9, 2023</results_first_submitted>
  <results_first_submitted_qc>March 14, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">March 21, 2023</results_first_posted>
  <last_update_submitted>August 25, 2023</last_update_submitted>
  <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Toxemia</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Hepatitis, Alcoholic</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>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 21, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT03829683/Prot_SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 20, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT03829683/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Vitamin C Infusion (Ascorbic Acid)</title>
          <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)&#xD;
Vitamin C: 200mg/kg/24hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Discharge from hospital</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Vitamin C Infusion (Ascorbic Acid)</title>
          <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)&#xD;
Vitamin C: 200mg/kg/24hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</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="10"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="20"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40.1" spread="9.5"/>
                    <measurement group_id="B2" value="48.4" spread="14.9"/>
                    <measurement group_id="B3" value="46.9" spread="12.5"/>
                  </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="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</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>Asian</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>Native Hawaiian or Other Pacific Islander</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>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Model for End Stage Liver Disease (MELD) Score</title>
        <description>Change in MELD score from Day 0 to Day 4. MELD score ranges from 6 (least sick) to 40 (most sick) based on blood tests which ranks the degree of sickness from liver disease. The lab tests used to determine the MELD score are creatinine, bilirubin, and international normalized ratio (INR).</description>
        <time_frame>Baseline and 96 hours</time_frame>
        <population>Labs were not collected from 4 participants on day 4 so change in MELD score could not be calculated for those participants and they are omitted from the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Vitamin C Infusion (Ascorbic Acid)</title>
            <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)&#xD;
Vitamin C: 200mg/kg/24hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Model for End Stage Liver Disease (MELD) Score</title>
          <description>Change in MELD score from Day 0 to Day 4. MELD score ranges from 6 (least sick) to 40 (most sick) based on blood tests which ranks the degree of sickness from liver disease. The lab tests used to determine the MELD score are creatinine, bilirubin, and international normalized ratio (INR).</description>
          <population>Labs were not collected from 4 participants on day 4 so change in MELD score could not be calculated for those participants and they are omitted from the analysis.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>All patients</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.13" spread="7.0"/>
                    <measurement group_id="O2" value="-2.9" spread="3.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Patients alive at 4 weeks</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.3" spread="5.2"/>
                    <measurement group_id="O2" value="-2.4" spread="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) Score</title>
        <description>A number that ranges from 0 (least sick) to 24 (most sick) and ranks the degree of sickness from liver failure and several other organ systems in a critically ill person. The score is determined by evaluating a person's liver function, kidney function, nervous system (brain), coagulation (blood clotting), circulation (blood pressure), and respiratory status (breathing)</description>
        <time_frame>Baseline and 96 hours</time_frame>
        <population>Data not recorded for all participants</population>
        <group_list>
          <group group_id="O1">
            <title>Vitamin C Infusion (Ascorbic Acid)</title>
            <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)&#xD;
Vitamin C: 200mg/kg/24hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) Score</title>
          <description>A number that ranges from 0 (least sick) to 24 (most sick) and ranks the degree of sickness from liver failure and several other organ systems in a critically ill person. The score is determined by evaluating a person's liver function, kidney function, nervous system (brain), coagulation (blood clotting), circulation (blood pressure), and respiratory status (breathing)</description>
          <population>Data not recorded for all participants</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14" spread="NA">Only 1 participant in this arm</measurement>
                    <measurement group_id="O2" value="15.33" spread="0.577"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="12.75" spread="1.708"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Aspartate Aminotransferase (AST) Level</title>
        <description>Standard blood test used to determine the severity and nature of liver problems.</description>
        <time_frame>Baseline and 96 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vitamin C Infusion (Ascorbic Acid)</title>
            <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)&#xD;
Vitamin C: 200mg/kg/24hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Aspartate Aminotransferase (AST) Level</title>
          <description>Standard blood test used to determine the severity and nature of liver problems.</description>
          <units>IU/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="176.0" spread="466.28"/>
                    <measurement group_id="O2" value="-16.5" spread="53.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Alanine Aminotransferase (ALT) Level</title>
        <description>Standard blood test used to determine the severity and nature of liver problems.</description>
        <time_frame>Baseline and 96 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vitamin C Infusion (Ascorbic Acid)</title>
            <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)&#xD;
Vitamin C: 200mg/kg/24hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Alanine Aminotransferase (ALT) Level</title>
          <description>Standard blood test used to determine the severity and nature of liver problems.</description>
          <units>IU/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.71" spread="155.26"/>
                    <measurement group_id="O2" value="1.00" spread="14.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Total Bilirubin</title>
        <description>Standard blood test used to determine the severity and nature of liver problems.</description>
        <time_frame>Baseline and 96 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vitamin C Infusion (Ascorbic Acid)</title>
            <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)&#xD;
Vitamin C: 200mg/kg/24hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Total Bilirubin</title>
          <description>Standard blood test used to determine the severity and nature of liver problems.</description>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.30" spread="5.69"/>
                    <measurement group_id="O2" value="0.45" spread="5.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Alkaline Phosphatase</title>
        <description>Standard blood test used to determine the severity and nature of liver problems.</description>
        <time_frame>Baseline and 96 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vitamin C Infusion (Ascorbic Acid)</title>
            <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)&#xD;
Vitamin C: 200mg/kg/24hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Alkaline Phosphatase</title>
          <description>Standard blood test used to determine the severity and nature of liver problems.</description>
          <units>U/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.71" spread="67.90"/>
                    <measurement group_id="O2" value="-7.50" spread="52.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Albumin</title>
        <description>Standard blood test used to determine the severity and nature of liver problems.</description>
        <time_frame>Baseline and 96 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vitamin C Infusion (Ascorbic Acid)</title>
            <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)&#xD;
Vitamin C: 200mg/kg/24hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Albumin</title>
          <description>Standard blood test used to determine the severity and nature of liver problems.</description>
          <units>g/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.10" spread="0.71"/>
                    <measurement group_id="O2" value="0.06" spread="0.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Treatment-related Adverse Events as Assessed by CTCAE v5.0</title>
        <description>Observation about the need to change the dose of study medication and symptoms such as headache, dizziness, dry mouth, nausea, vomiting, flushing, rash, or hypotension (low blood pressure)</description>
        <time_frame>up to 96 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vitamin C Infusion (Ascorbic Acid)</title>
            <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)&#xD;
Vitamin C: 200mg/kg/24hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Treatment-related Adverse Events as Assessed by CTCAE v5.0</title>
          <description>Observation about the need to change the dose of study medication and symptoms such as headache, dizziness, dry mouth, nausea, vomiting, flushing, rash, or hypotension (low blood pressure)</description>
          <units>Adverse Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes to Corrected QT Interval (QTc)</title>
        <description>An electrocardiogram (ECG or test of the electrical activity of the heart) is performed to determine if there are changes to the heart rhythm.</description>
        <time_frame>Baseline and 96 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vitamin C Infusion (Ascorbic Acid)</title>
            <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)&#xD;
Vitamin C: 200mg/kg/24hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Changes to Corrected QT Interval (QTc)</title>
          <description>An electrocardiogram (ECG or test of the electrical activity of the heart) is performed to determine if there are changes to the heart rhythm.</description>
          <units>milliseconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.00" spread="29.47"/>
                    <measurement group_id="O2" value="-58.17" spread="88.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes to Urine pH</title>
        <description>Urine samples are collected to determine changes in pH (acidity) that could indicate a risk for kidney stones. The pH scale ranges from 0 to 14, with smaller numbers meaning more acidic and higher numbers meaning more basic. A pH of 7 is considered to be neutral. Normal levels of urine pH range from 4.6 - 8 on the pH scale.</description>
        <time_frame>Baseline and 96 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vitamin C Infusion (Ascorbic Acid)</title>
            <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)&#xD;
Vitamin C: 200mg/kg/24hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Changes to Urine pH</title>
          <description>Urine samples are collected to determine changes in pH (acidity) that could indicate a risk for kidney stones. The pH scale ranges from 0 to 14, with smaller numbers meaning more acidic and higher numbers meaning more basic. A pH of 7 is considered to be neutral. Normal levels of urine pH range from 4.6 - 8 on the pH scale.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.31" spread="2.01"/>
                    <measurement group_id="O2" value="5.17" spread="0.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes to Urine Microscopy</title>
        <description>Urine samples are collected to check for the presence of crystalluria (microscopic crystals) that could indicate a risk for kidney stones.</description>
        <time_frame>Baseline and 96 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vitamin C Infusion (Ascorbic Acid)</title>
            <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)&#xD;
Vitamin C: 200mg/kg/24hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Changes to Urine Microscopy</title>
          <description>Urine samples are collected to check for the presence of crystalluria (microscopic crystals) that could indicate a risk for kidney stones.</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="8"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Number of participants with crystalluria at baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of patients with crystalluria at Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes to Level of Medical Care</title>
        <description>Documentation of the need for more intensive medical care such as ventilator (breathing machine) or vasopressors (intravenous medications use increase blood pressure) when not needed at baseline</description>
        <time_frame>up to 168 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vitamin C Infusion (Ascorbic Acid)</title>
            <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)&#xD;
Vitamin C: 200mg/kg/24hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Changes to Level of Medical Care</title>
          <description>Documentation of the need for more intensive medical care such as ventilator (breathing machine) or vasopressors (intravenous medications use increase blood pressure) when not needed at baseline</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="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ICU-free Days</title>
        <description>The number of days not spent in an intensive care unit (ICU)</description>
        <time_frame>Day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vitamin C Infusion (Ascorbic Acid)</title>
            <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)&#xD;
Vitamin C: 200mg/kg/24hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
        </group_list>
        <measure>
          <title>ICU-free Days</title>
          <description>The number of days not spent in an intensive care unit (ICU)</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.40" spread="14.17"/>
                    <measurement group_id="O2" value="13.20" spread="13.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Deaths Due to Any Cause</title>
        <description>Any cause of death that is anticipated or unanticipated</description>
        <time_frame>Day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vitamin C Infusion (Ascorbic Acid)</title>
            <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)&#xD;
Vitamin C: 200mg/kg/24hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Deaths Due to Any Cause</title>
          <description>Any cause of death that is anticipated or unanticipated</description>
          <units>Deaths</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Deaths Due to Any Cause</title>
        <description>Any cause of death that is anticipated or unanticipated</description>
        <time_frame>Day 90</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vitamin C Infusion (Ascorbic Acid)</title>
            <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)&#xD;
Vitamin C: 200mg/kg/24hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Deaths Due to Any Cause</title>
          <description>Any cause of death that is anticipated or unanticipated</description>
          <units>Deaths</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hospital-free Days</title>
        <description>The number of days spent outside of the hospital</description>
        <time_frame>Day 90</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vitamin C Infusion (Ascorbic Acid)</title>
            <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)&#xD;
Vitamin C: 200mg/kg/24hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
          </group>
        </group_list>
        <measure>
          <title>Hospital-free Days</title>
          <description>The number of days spent outside of the hospital</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58.40" spread="32.91"/>
                    <measurement group_id="O2" value="48.88" spread="33.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 90 days after drug infusion</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Vitamin C Infusion (Ascorbic Acid)</title>
          <description>Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)&#xD;
Vitamin C: 200mg/kg/24hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours&#xD;
Dextrose 5% in water: 50mL intravenously every 6 hours</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Weakness, hospitalization</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Electrocardiogram QT corrected interval</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>QT interval prolonged</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hypophospahtemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Bladder spasm</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </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>Arun J Sanyal, MD</name_or_title>
      <organization>Virginia Commonwealth University</organization>
      <phone>804-828-4060</phone>
      <email>arun.sanyal@vcuhealth.org</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/NCT03829683
org study id: HM20014364
secondary id: U01AA026966
nct id: NCT03829683
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this research study is to test the safety, tolerability, and effectiveness of
      Vitamin C (ascorbic acid) intravenous infusion when used to treat alcoholic hepatitis
      (inflammation of the liver from heavy alcohol use) and sepsis (life-threatening complication
      of an infection).
Alcoholic hepatitis is inflammation of the liver due to alcohol consumption. It can cause one
      or more of the following symptoms such as jaundice (yellow discoloration of the eyes and
      skin), pain on the right side of the abdomen, and is accompanied by an enlarged liver. Sepsis
      is a life-threatening complication of an infection. As the body tries to fight an infection
      it sends chemicals into the bloodstream. These chemicals that are trying to fight the
      infection can cause inflammation. This inflammation can cause damage to many body systems and
      make them fail. Patients with alcoholic hepatitis and sepsis have low levels of Vitamin C in
      the bloodstream. Vitamin C has been shown to reduce inflammation and organ dysfunction in
      patients with severe infections.

      The investigators do not yet know if Vitamin C will be effective in alcoholic hepatitis.
      Taking Vitamin C by mouth is not effective as a treatment in people with this condition so
      participants will receive the Vitamin C intravenously (IV). Participants will be randomly
      assigned to receive either Vitamin C or a placebo given through an IV every six hours for
      four days.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Study drug will be double-blind with matching placebo. Vitamin C 200mg/kg/24hours or placebo (Dextrose 5% in water) will be given intravenously every 6 hours for up to 96 hours of treatment.
measure: Change in Model for End Stage Liver Disease (MELD) Score
time frame: Baseline and 96 hours
description: Change in MELD score from Day 0 to Day 4. MELD score ranges from 6 (least sick) to 40 (most sick) based on blood tests which ranks the degree of sickness from liver disease. The lab tests used to determine the MELD score are creatinine, bilirubin, and international normalized ratio (INR).
measure: Change in Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) Score
time frame: Baseline and 96 hours
description: A number that ranges from 0 (least sick) to 24 (most sick) and ranks the degree of sickness from liver failure and several other organ systems in a critically ill person. The score is determined by evaluating a person's liver function, kidney function, nervous system (brain), coagulation (blood clotting), circulation (blood pressure), and respiratory status (breathing)
measure: Change in Aspartate Aminotransferase (AST) Level
time frame: Baseline and 96 hours
description: Standard blood test used to determine the severity and nature of liver problems.
measure: Change in Alanine Aminotransferase (ALT) Level
time frame: Baseline and 96 hours
description: Standard blood test used to determine the severity and nature of liver problems.
measure: Change in Total Bilirubin
time frame: Baseline and 96 hours
description: Standard blood test used to determine the severity and nature of liver problems.
measure: Change in Alkaline Phosphatase
time frame: Baseline and 96 hours
description: Standard blood test used to determine the severity and nature of liver problems.
measure: Change in Albumin
time frame: Baseline and 96 hours
description: Standard blood test used to determine the severity and nature of liver problems.
measure: Number of Treatment-related Adverse Events as Assessed by CTCAE v5.0
time frame: up to 96 hours
description: Observation about the need to change the dose of study medication and symptoms such as headache, dizziness, dry mouth, nausea, vomiting, flushing, rash, or hypotension (low blood pressure)
measure: Changes to Corrected QT Interval (QTc)
time frame: Baseline and 96 hours
description: An electrocardiogram (ECG or test of the electrical activity of the heart) is performed to determine if there are changes to the heart rhythm.
measure: Changes to Urine pH
time frame: Baseline and 96 hours
description: Urine samples are collected to determine changes in pH (acidity) that could indicate a risk for kidney stones. The pH scale ranges from 0 to 14, with smaller numbers meaning more acidic and higher numbers meaning more basic. A pH of 7 is considered to be neutral. Normal levels of urine pH range from 4.6 - 8 on the pH scale.
measure: Changes to Urine Microscopy
time frame: Baseline and 96 hours
description: Urine samples are collected to check for the presence of crystalluria (microscopic crystals) that could indicate a risk for kidney stones.
measure: Changes to Level of Medical Care
time frame: up to 168 hours
description: Documentation of the need for more intensive medical care such as ventilator (breathing machine) or vasopressors (intravenous medications use increase blood pressure) when not needed at baseline
measure: ICU-free Days
time frame: Day 28
description: The number of days not spent in an intensive care unit (ICU)
measure: Number of Deaths Due to Any Cause
time frame: Day 28
description: Any cause of death that is anticipated or unanticipated
measure: Number of Deaths Due to Any Cause
time frame: Day 90
description: Any cause of death that is anticipated or unanticipated
measure: Hospital-free Days
time frame: Day 90
description: The number of days spent outside of the hospital
arm group label: Vitamin C infusion (ascorbic acid)
arm group type: Active Comparator
description: Vitamin C 200mg/kg/24hours administered in four doses per day (given every 6 hours)
arm group label: Placebo
arm group type: Placebo Comparator
description: Dextrose 5% in water 50 milliliters (mL) administered intravenously every 6 hours
intervention type: Drug
intervention name: Vitamin C
description: 200mg/kg/24hours
arm group label: Vitamin C infusion (ascorbic acid)
other name: ascorbic acid
other name: AscA
other name: Ascor
intervention type: Drug
intervention name: Dextrose 5% in water
description: 50mL intravenously every 6 hours
arm group label: Placebo
arm group label: Vitamin C infusion (ascorbic acid)
other name: D5W
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Arun J Sanyal, MD
role: Principal Investigator
affiliation: Virginia Commonwealth University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hepatitis A
mesh term: Sepsis
mesh term: Toxemia
mesh term: Hepatitis
mesh term: Hepatitis, Alcoholic
mesh term: Ascorbic Acid
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 