<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/NCT04494451</url>
  </required_header>
  <id_info>
    <org_study_id>ILBS-Cirrhosis-35</org_study_id>
    <nct_id>NCT04494451</nct_id>
  </id_info>
  <brief_title>Efficacy of Vitamin C on AKI Outcomes in Critically Ill Cirrhotics With Multidrug-resistant Bacterial Infections.</brief_title>
  <official_title>Efficacy of Vitamin C on AKI Outcomes in Critically Ill Cirrhotics With Multidrug-resistant Bacterial Infections- A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Institute of Liver and Biliary Sciences, India</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Institute of Liver and Biliary Sciences, India</source>
  <oversight_info>
    <has_dmc>No</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>
      In this prospective randomized controlled trial we aim to evaluate the impact of vitamin C on&#xD;
      AKI outcomes in patients with cirrhosis and MDR infections. We also aim to evaluate the&#xD;
      effects of iv vitamin c on systemic hemodynamics (cardiac output and systemic vascular&#xD;
      resistive index, extravascular lung water and lung permeability index), endothelial function&#xD;
      and coagulation, microcirculation (as assessed by lactate clearance and central venous oxygen&#xD;
      saturation), mitochondrial function, 28-day mortality and vasopressor, ventilator and RRT&#xD;
      free days in the ICU. The safety and side-effects of vitamin c would also be evaluated.&#xD;
&#xD;
      Patients with suspected (nosocomial acquisition) or proven MDR infections would be screened&#xD;
      and randomized to two groups who meet the inclusion and exclusion criteria.&#xD;
&#xD;
      Group 1: Will receive iv vitamin C (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5&#xD;
      days along with iv antibiotics as per institutional protocol Group 2: iv antibiotics alone&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Aim &amp; Objectives Primary To evaluate the impact of vitamin C on AKI outcomes in patients with&#xD;
      cirrhosis and MDR infections&#xD;
&#xD;
      Secondary Objectives To assess the effects on systemic hemodynamics (cardiac output and&#xD;
      systemic vascular resistive index, extravascular lung water and lung permeability index)&#xD;
      Impact of Vitamin C on endothelial function and coagulation Improvement in microcirculation&#xD;
      as assessed by lactate clearance and central venous oxygen saturation To assess the effects&#xD;
      on 28-day mortality. Improvement in SOFA scores in both groups Vasopressor, ventilator and&#xD;
      RRT free days in the ICU Incidence of adverse effects in both groups Prevalence of vitamin C&#xD;
      deficiency in cirrhotics with sepsis and impact of exogenous vitamin C in improving&#xD;
      endogenous levels of ascorbate and norepinephrine levels Impact of vitamin C on oxidative&#xD;
      stress by evaluation of mitochondrial bioenergetics&#xD;
&#xD;
      (B) Methodology Patients with suspected (nosocomial acquisition) or proven MDR infections&#xD;
      would be screened and randomized to two groups as under Group 1: Will receive iv vitamin C&#xD;
      (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5 days along with iv antibiotics as&#xD;
      per institutional protocol Group 2: iv antibiotics alone All patients with nosocomial&#xD;
      bacterial infections or septic shock would be screened for randomization would be considered&#xD;
      for enrolment in the trial. Nosocomial infection would be defined as infections developing&#xD;
      after 48 hours of hospitalization. Following this, patients meeting the inclusion and&#xD;
      exclusion criteria will be screened and randomized to the two treatment groups. Standard of&#xD;
      care for management of antibiotics, fluids and vasopressors would be as per institutional&#xD;
      guidelines. At baseline, blood and urine sample would be stored for all patients for&#xD;
      performing mitochondrial bioenergetics, endotoxin, proinflammatory cytokines (IL-6, IL-IB,&#xD;
      TNF-alpha, MCP-1, IL-1O) and urine biomarkers (urine NGAL and cystatin C) and markers of&#xD;
      endothelial dysfunction(von willebrand factor and ADAMTS). Following randomization patients&#xD;
      would be allocated to receive intravenous vitamin C (1.5 g every 6 h or 25 mg/kg for 5 days)&#xD;
      along with intravenous antibiotics&#xD;
&#xD;
      Study Population:&#xD;
&#xD;
      Patients with cirrhosis with MDR infections (nosocomial acquisition) or culture-proven&#xD;
&#xD;
      Study Design:&#xD;
&#xD;
        -  A randomized controlled study.&#xD;
&#xD;
        -  The study will be conducted on patients admitted to Department of Hepatology from June&#xD;
           2020 to December 2020 at ILBS, New Delhi&#xD;
&#xD;
        -  Study group will comprise of patients critically ill cirrhotics with suspected or proven&#xD;
           MDR infections&#xD;
&#xD;
      Study period&#xD;
&#xD;
        -  The study will be conducted on patients admitted to Department of Hepatology from June&#xD;
           2020 to December 2020 at ILBS, New Delhi&#xD;
&#xD;
        -  Study group will comprise of patients critically ill cirrhotics with MDR infections.&#xD;
&#xD;
      Sample Size calculation: Currently there are lack of studies investigating the incidence and&#xD;
      outcomes of AKI in this context. The study will be designed as a pilot RCT with an aim to&#xD;
      enrol 50 patients in each group.&#xD;
&#xD;
      The detailed cytokine profile, endotoxin assay, markers of endothelial dysfunction and&#xD;
      bioenergetics would be performed in a subset of 15 patients in each group.&#xD;
&#xD;
      Intervention: IV Vitamin C&#xD;
&#xD;
      Monitoring and Assessment: Hourly till the patient is in the intensive care unit then every 7&#xD;
      days for 1 month&#xD;
&#xD;
      Statistical analysis&#xD;
&#xD;
        -  All variables shall be expressed in mean (sd) or median (range)&#xD;
&#xD;
        -  Variables will be compared by Mann- Whitney U test&#xD;
&#xD;
        -  For Categorical variables we will use Chi-Square or Fisher's test&#xD;
&#xD;
        -  Survival analysis will be done using Cox-proportional regression analysis&#xD;
&#xD;
      Actuarial probability of survival shall be calculated by Kaplan- Meier graph and compared by&#xD;
      log- rank test.&#xD;
&#xD;
      Adverse Effects: Any allergic reactions, drop in hemoglobin or development of kidney stones&#xD;
&#xD;
      Stopping rule of the study: Any untoward adverse effects of the intervention.&#xD;
&#xD;
      Ethical issues in the study and plans to address these issue The study is designed to&#xD;
      demonstrate the efficacy of intravenous vitamin C in improving AKI outcomes in cirrhotics&#xD;
      with MDR infections. Vitamin C is been routinely used in this indication with no major&#xD;
      adverse effects. However, head-to-head comparison is needed to identify the evidence and&#xD;
      benefits of using this drug in this indication. Only minor side effects like nausea,&#xD;
      diarrhea, abdominal bloating, cramps and precipitation of kidney stones have been observed&#xD;
      with the drug.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 25, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AKI progression at day 5</measure>
    <time_frame>Day 5</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mortality in both groups</measure>
    <time_frame>Day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to reversal of AKI in both groups</measure>
    <time_frame>Day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lactate clearance in both groups</measure>
    <time_frame>12 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lactate clearance in both groups</measure>
    <time_frame>24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vasopressor, ventilator and days free of dialysis during ICU stay</measure>
    <time_frame>Day 28</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Liver Cirrhosis</condition>
  <arm_group>
    <arm_group_label>Vitamin C + Standard Medical Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>vitamin C (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5 days along with iv antibiotics as per institutional protocol along with iv antibiotics</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard Medical Treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>iv antibiotics alone</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vit C</intervention_name>
    <description>vitamin C (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5 day</description>
    <arm_group_label>Vitamin C + Standard Medical Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard medical Treatment</intervention_name>
    <description>iv antibiotics alone</description>
    <arm_group_label>Standard Medical Treatment</arm_group_label>
    <arm_group_label>Vitamin C + Standard Medical Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Critically ill cirrhotics with MDR infections&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with age less than 18 years&#xD;
&#xD;
          -  Known severe cardiopulmonary disease (structural or valvular heart disease, coronary&#xD;
             artery disease, COPD)&#xD;
&#xD;
          -  Patients in DIC with platelets &lt; 20,000 and INR &gt; 4 or active bleeding&#xD;
&#xD;
          -  Limitations of care (defined as refusal of cardiovascular and respiratory support&#xD;
             modes) including &quot;do not intubate&quot; (DNI) status&#xD;
&#xD;
          -  Current hospitalization &gt; 15 days for patients with nosocomial acquisition of MDR at&#xD;
             time of randomization&#xD;
&#xD;
          -  Known allergy or contraindication to vitamin C (including previously or currently&#xD;
             diagnosed primary hyperoxaluria and/or oxalate nephropathy, or known/suspected&#xD;
             ethylene glycol ingestion,&#xD;
&#xD;
          -  Known glucose-6-phosphate dehydrogenase (G6PD) deficiency)&#xD;
&#xD;
          -  Use of vitamin C at a dose of &gt; 1 gram daily within the 24 hours preceding first&#xD;
             episode of qualifying organ dysfunction during a given ED or ICU admission&#xD;
&#xD;
          -  Patients with HCC (beyond Milan) or extrahepatic malignancies&#xD;
&#xD;
          -  Patients with HVOTO or EHPVO&#xD;
&#xD;
          -  Pregnancy or active breastfeeding&#xD;
&#xD;
          -  Current participation in another interventional research study&#xD;
&#xD;
          -  Active or history of kidney stone&#xD;
&#xD;
          -  History of chronic kidney disease or intrinsic kidney disease&#xD;
&#xD;
          -  Patients already on maintenance hemodialysis prior to presentation&#xD;
&#xD;
          -  Patients with refractory septic shock or hypoxemia (Pa02/Fio2 ratio &lt;100)&#xD;
&#xD;
          -  Extremely moribund patients with an expected life expectancy of less than 24 hours&#xD;
&#xD;
          -  Failure to provide informed consent&#xD;
&#xD;
          -  Patients with retroviral infection&#xD;
&#xD;
          -  Patients with acute on chronic liver failure (APASL definition)&#xD;
&#xD;
          -  Patients with urinary tract infection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Dr Rakhi Maiwall, DM</last_name>
    <phone>01146300000</phone>
    <email>rakhi_2011@yahoo.co.in</email>
  </overall_contact>
  <location>
    <facility>
      <name>Institute of Liver &amp; Biliary Sciences</name>
      <address>
        <city>New Delhi</city>
        <state>Delhi</state>
        <zip>110070</zip>
        <country>India</country>
      </address>
    </facility>
    <contact>
      <last_name>Dr Rakhi Maiwall, DM</last_name>
      <phone>01146300000</phone>
      <email>rakhi_2011@yahoo.co.in</email>
    </contact>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 28, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2020</study_first_posted>
  <last_update_submitted>July 28, 2020</last_update_submitted>
  <last_update_submitted_qc>July 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 31, 2020</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>Bacterial Infections</mesh_term>
    <mesh_term>Liver Cirrhosis</mesh_term>
  </condition_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/NCT04494451
org study id: ILBS-Cirrhosis-35
nct id: NCT04494451
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
In this prospective randomized controlled trial we aim to evaluate the impact of vitamin C on
      AKI outcomes in patients with cirrhosis and MDR infections. We also aim to evaluate the
      effects of iv vitamin c on systemic hemodynamics (cardiac output and systemic vascular
      resistive index, extravascular lung water and lung permeability index), endothelial function
      and coagulation, microcirculation (as assessed by lactate clearance and central venous oxygen
      saturation), mitochondrial function, 28-day mortality and vasopressor, ventilator and RRT
      free days in the ICU. The safety and side-effects of vitamin c would also be evaluated.

      Patients with suspected (nosocomial acquisition) or proven MDR infections would be screened
      and randomized to two groups who meet the inclusion and exclusion criteria.

      Group 1: Will receive iv vitamin C (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5
      days along with iv antibiotics as per institutional protocol Group 2: iv antibiotics alone
Aim & Objectives Primary To evaluate the impact of vitamin C on AKI outcomes in patients with
      cirrhosis and MDR infections

      Secondary Objectives To assess the effects on systemic hemodynamics (cardiac output and
      systemic vascular resistive index, extravascular lung water and lung permeability index)
      Impact of Vitamin C on endothelial function and coagulation Improvement in microcirculation
      as assessed by lactate clearance and central venous oxygen saturation To assess the effects
      on 28-day mortality. Improvement in SOFA scores in both groups Vasopressor, ventilator and
      RRT free days in the ICU Incidence of adverse effects in both groups Prevalence of vitamin C
      deficiency in cirrhotics with sepsis and impact of exogenous vitamin C in improving
      endogenous levels of ascorbate and norepinephrine levels Impact of vitamin C on oxidative
      stress by evaluation of mitochondrial bioenergetics

      (B) Methodology Patients with suspected (nosocomial acquisition) or proven MDR infections
      would be screened and randomized to two groups as under Group 1: Will receive iv vitamin C
      (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5 days along with iv antibiotics as
      per institutional protocol Group 2: iv antibiotics alone All patients with nosocomial
      bacterial infections or septic shock would be screened for randomization would be considered
      for enrolment in the trial. Nosocomial infection would be defined as infections developing
      after 48 hours of hospitalization. Following this, patients meeting the inclusion and
      exclusion criteria will be screened and randomized to the two treatment groups. Standard of
      care for management of antibiotics, fluids and vasopressors would be as per institutional
      guidelines. At baseline, blood and urine sample would be stored for all patients for
      performing mitochondrial bioenergetics, endotoxin, proinflammatory cytokines (IL-6, IL-IB,
      TNF-alpha, MCP-1, IL-1O) and urine biomarkers (urine NGAL and cystatin C) and markers of
      endothelial dysfunction(von willebrand factor and ADAMTS). Following randomization patients
      would be allocated to receive intravenous vitamin C (1.5 g every 6 h or 25 mg/kg for 5 days)
      along with intravenous antibiotics

      Study Population:

      Patients with cirrhosis with MDR infections (nosocomial acquisition) or culture-proven

      Study Design:

        -  A randomized controlled study.

        -  The study will be conducted on patients admitted to Department of Hepatology from June
           2020 to December 2020 at ILBS, New Delhi

        -  Study group will comprise of patients critically ill cirrhotics with suspected or proven
           MDR infections

      Study period

        -  The study will be conducted on patients admitted to Department of Hepatology from June
           2020 to December 2020 at ILBS, New Delhi

        -  Study group will comprise of patients critically ill cirrhotics with MDR infections.

      Sample Size calculation: Currently there are lack of studies investigating the incidence and
      outcomes of AKI in this context. The study will be designed as a pilot RCT with an aim to
      enrol 50 patients in each group.

      The detailed cytokine profile, endotoxin assay, markers of endothelial dysfunction and
      bioenergetics would be performed in a subset of 15 patients in each group.

      Intervention: IV Vitamin C

      Monitoring and Assessment: Hourly till the patient is in the intensive care unit then every 7
      days for 1 month

      Statistical analysis

        -  All variables shall be expressed in mean (sd) or median (range)

        -  Variables will be compared by Mann- Whitney U test

        -  For Categorical variables we will use Chi-Square or Fisher's test

        -  Survival analysis will be done using Cox-proportional regression analysis

      Actuarial probability of survival shall be calculated by Kaplan- Meier graph and compared by
      log- rank test.

      Adverse Effects: Any allergic reactions, drop in hemoglobin or development of kidney stones

      Stopping rule of the study: Any untoward adverse effects of the intervention.

      Ethical issues in the study and plans to address these issue The study is designed to
      demonstrate the efficacy of intravenous vitamin C in improving AKI outcomes in cirrhotics
      with MDR infections. Vitamin C is been routinely used in this indication with no major
      adverse effects. However, head-to-head comparison is needed to identify the evidence and
      benefits of using this drug in this indication. Only minor side effects like nausea,
      diarrhea, abdominal bloating, cramps and precipitation of kidney stones have been observed
      with the drug.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AKI progression at day 5
time frame: Day 5
measure: Mortality in both groups
time frame: Day 28
measure: Time to reversal of AKI in both groups
time frame: Day 14
measure: Lactate clearance in both groups
time frame: 12 hours
measure: Lactate clearance in both groups
time frame: 24 hours
measure: Vasopressor, ventilator and days free of dialysis during ICU stay
time frame: Day 28
arm group label: Vitamin C + Standard Medical Treatment
arm group type: Experimental
description: vitamin C (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5 days along with iv antibiotics as per institutional protocol along with iv antibiotics
arm group label: Standard Medical Treatment
arm group type: Active Comparator
description: iv antibiotics alone
intervention type: Drug
intervention name: Vit C
description: vitamin C (25 mg/kg or max. 1.5 gram every 6 hourly) for maximum 5 day
arm group label: Vitamin C + Standard Medical Treatment
intervention type: Drug
intervention name: Standard medical Treatment
description: iv antibiotics alone
arm group label: Standard Medical Treatment
arm group label: Vitamin C + Standard Medical Treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Dr Rakhi Maiwall, DM
phone: 01146300000
email: rakhi_2011@yahoo.co.in
facility: 
contact: 
country: India
responsible party type: Sponsor
mesh term: Bacterial Infections
mesh term: Liver Cirrhosis
sharing ipd: Undecided