<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/NCT04505878</url>
  </required_header>
  <id_info>
    <org_study_id>2020-0503</org_study_id>
    <secondary_id>A530900</secondary_id>
    <secondary_id>SMPH/ANESTHESIOLOGY</secondary_id>
    <secondary_id>Protocol Version 0.05</secondary_id>
    <nct_id>NCT04505878</nct_id>
  </id_info>
  <brief_title>Perioperative Vitamin C Lung Transplant</brief_title>
  <official_title>Vitamin C: Assessing Safety After Lung Transplant</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Wisconsin, Madison</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Wisconsin, Madison</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>
      This study is being done to determine if parenterally administered ascorbic acid (Vitamin C)&#xD;
      given at the time of lung transplant is safe. Vitamin C may be an effective intervention&#xD;
      towards primary graft dysfunction (PGD). The study will enroll 69 participants who consent to&#xD;
      the intervention. Participants who do not consent to the intervention will be treated&#xD;
      according to standard-of-care, but may choose to be consented to have their data&#xD;
      retrospectively reviewed. Based on our consent rate, this group may include 40-70&#xD;
      participants. Participants will be on study for up to 12 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PGD is a frequent and severe outcome that impacts both short- and long-term outcomes after&#xD;
      lung transplantation. Major pathophysiologic contributors include ischemia and reperfusion&#xD;
      injury, mitochondrial dysfunction and endothelial failure. No directed therapy exists.&#xD;
      Vitamin C is a first-line antioxidant that also acts at the endothelium and mitochondria to&#xD;
      decrease permeability and leak, inhibit mitochondrial dysfunction and improve ischemia and&#xD;
      reperfusion. When combined with steroids, part of standard care for lung transplant&#xD;
      recipients, these effects may be enhanced and synergistically inhibit instigators of patient&#xD;
      injury. A pilot trial will ensure safety of this potential intervention and guide future&#xD;
      research into this important outcome measure. It will be readily received in the literature.&#xD;
&#xD;
      For the present study, vitamin C will be administered parenterally at a dose of 1,500 mg&#xD;
      every 6 hours, a dose that is widely accepted and used in other clinical contexts where the&#xD;
      drug is studied, such as sepsis. This will predictably reconstitute levels and achieve&#xD;
      supratherapeutic benefit towards oxidant scavenging, while avoiding the potential pro-oxidant&#xD;
      effects seen at exceedingly high doses. To this end, the investigators will exclude patients&#xD;
      where the standard dosing of vitamin C will exceed 100 mg/kg/day (excluding patients &lt;60 kg).&#xD;
      Dosing will continue through post-operative day (POD) 3 to effectively assess for the impact&#xD;
      of vitamin C on PGD.&#xD;
&#xD;
      Primary Objectives&#xD;
&#xD;
        -  To assess whether parenterally administered ascorbic acid (vitamin C) is safe in the&#xD;
           lung transplant population&#xD;
&#xD;
        -  To estimate adherence to ascorbic acid administration protocol in this study population&#xD;
           and to identify obstacles to feasibility of future trials using this protocol&#xD;
&#xD;
      Secondary Objectives&#xD;
&#xD;
        -  To assess whether parenterally administered ascorbic acid (vitamin C) may decrease the&#xD;
           rate and severity of PGD after lung transplant&#xD;
&#xD;
        -  To establish the incidence of vitamin C and vitamin B1 (thiamine) deficiencies in the&#xD;
           lung transplant population, and the responsiveness of vitamin C levels to our selected&#xD;
           parenteral therapy&#xD;
&#xD;
        -  To identify interventions that will optimize the post-operative wellbeing of patients&#xD;
           receiving lung transplants by decreasing primary graft dysfunction (short and&#xD;
           intermediate-to-long term&#xD;
&#xD;
      Stop Criteria&#xD;
&#xD;
        -  Anuria x 3-hours&#xD;
&#xD;
        -  Moderate, Grade 2 AKI (doubling of baseline creatinine)&#xD;
&#xD;
        -  An acute, unexplained hemoglobin drop of &gt;2 mg/dL&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Decided not to proceed with study&#xD;
  </why_stopped>
  <start_date type="Anticipated">April 2023</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This is a pilot single-arm unblinded trial to assess whether parenterally administered ascorbic acid (vitamin C) is safe in the lung transplant population.The investigators will not randomize or control; a retrospective cohort of participants not treated with vitamin C will be reviewed from 2015-2020. Those participants who decline the intervention will have the choice to consent to having their data be considered as part of the (non-retrospective) controls and be considered in our statistical analysis for outcomes, including analysis between this group and the historical controls. All participants who consent will be administered the therapy and participants will be evaluated via an intention-to-treat analysis.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence and Severity of Kidney Injury Post Operative Day (POD) 1</measure>
    <time_frame>Post Operative Day 1</time_frame>
    <description>The primary endpoint is the safety of the vitamin C intervention. This will be measured by the incidence and severity of kidney injuries on POD 1, POD 2, POD 3, POD 4, and POD 7. Acute kidney injury (AKI) is defined as any creatinine (Cr) that is 1.5-times the participant's baseline / immediate preoperative creatinine. Severity escalates with increasing ratios: Mild, stage 1 AKI (Cr 1.5-1.99x baseline); Moderate, stage 2 AKI (Cr 2-2.9x baseline); and Severe, stage 3 AKI (Cr &gt;3x baseline or any initiation of dialysis).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence and Severity of Kidney Injury POD 2</measure>
    <time_frame>Post Operative Day 2</time_frame>
    <description>The primary endpoint is the safety of the vitamin C intervention. This will be measured by the incidence and severity of kidney injuries on POD 1, POD 2, POD 3, POD 4, and POD 7. Acute kidney injury (AKI) is defined as any creatinine (Cr) that is 1.5-times the participant's baseline / immediate preoperative creatinine. Severity escalates with increasing ratios: Mild, stage 1 AKI (Cr 1.5-1.99x baseline); Moderate, stage 2 AKI (Cr 2-2.9x baseline); and Severe, stage 3 AKI (Cr &gt;3x baseline or any initiation of dialysis).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence and Severity of Kidney Injury POD 3</measure>
    <time_frame>Post Operative Day 3</time_frame>
    <description>The primary endpoint is the safety of the vitamin C intervention. This will be measured by the incidence and severity of kidney injuries on POD 1, POD 2, POD 3, POD 4, and POD 7. Acute kidney injury (AKI) is defined as any creatinine (Cr) that is 1.5-times the participant's baseline / immediate preoperative creatinine. Severity escalates with increasing ratios: Mild, stage 1 AKI (Cr 1.5-1.99x baseline); Moderate, stage 2 AKI (Cr 2-2.9x baseline); and Severe, stage 3 AKI (Cr &gt;3x baseline or any initiation of dialysis).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence and Severity of Kidney Injury POD 4</measure>
    <time_frame>Post Operative Day 4</time_frame>
    <description>The primary endpoint is the safety of the vitamin C intervention. This will be measured by the incidence and severity of kidney injuries on POD 1, POD 2, POD 3, POD 4, and POD 7. Acute kidney injury (AKI) is defined as any creatinine (Cr) that is 1.5-times the participant's baseline / immediate preoperative creatinine. Severity escalates with increasing ratios: Mild, stage 1 AKI (Cr 1.5-1.99x baseline); Moderate, stage 2 AKI (Cr 2-2.9x baseline); and Severe, stage 3 AKI (Cr &gt;3x baseline or any initiation of dialysis).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence and Severity of Kidney Injury POD 7</measure>
    <time_frame>Post Operative Day 7</time_frame>
    <description>The primary endpoint is the safety of the vitamin C intervention. This will be measured by the incidence and severity of kidney injuries on POD 1, POD 2, POD 3, POD 4, and POD 7. Acute kidney injury (AKI) is defined as any creatinine (Cr) that is 1.5-times the participant's baseline / immediate preoperative creatinine. Severity escalates with increasing ratios: Mild, stage 1 AKI (Cr 1.5-1.99x baseline); Moderate, stage 2 AKI (Cr 2-2.9x baseline); and Severe, stage 3 AKI (Cr &gt;3x baseline or any initiation of dialysis).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of New Dialysis Initiation</measure>
    <time_frame>up to Post Operative Day 7</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Participant Vitamin C Levels</measure>
    <time_frame>Baseline, Post Operative Day 1, Post Operative Day 2, Post Operative Day 3</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participant Thiamine Levels</measure>
    <time_frame>Baseline, Post Operative Day 1, Post Operative Day 2, Post Operative Day 3</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Primary Graft Dysfunction (PGD)</measure>
    <time_frame>up to Post Operative Day 7</time_frame>
    <description>Primary Graft Dysfunction is defined as chest x-ray (CXR)-infiltrates with or without depressed oxygenation function, assessed by the &quot;PF-Ratio,&quot; which is the PaO2 / FiO2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and Severity of PGD on POD 3</measure>
    <time_frame>Post Operative Day 3</time_frame>
    <description>Primary Graft Dysfunction is defined as chest x-ray (CXR)-infiltrates with or without depressed oxygenation function, assessed by the &quot;PF-Ratio,&quot; which is the PaO2 / FiO2. Severity is defined as: PGD Grade 1 = CXR findings and any PF Ratio &gt; 300; PGD Grade 2 = CXR findings and PF Ratio 200-300; and PGD Grade 3 = CXR findings and PF Ratio &lt;200.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tacrolimus Levels</measure>
    <time_frame>Post Operative Days 2, 3, 4, and 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tacrolimus Doses</measure>
    <time_frame>Post Operative Days 4 and 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-Operative Well Being: Mortality</measure>
    <time_frame>at Post Operative Day 30 and Post Operative Day 90 via chart review</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-Operative Well Being: Atrial Fibrillation</measure>
    <time_frame>up to Post Operative Day 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-Operative Well Being: ICU Length of Stay</measure>
    <time_frame>up to Post Operative Day 30 (chart review)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-Operative Well Being: Hospital Length of Stay</measure>
    <time_frame>up to Post Operative Day 90 (chart review)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-Operative Well Being: Nadir Cardiac Index</measure>
    <time_frame>up to 72 hours post op</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-Operative Well Being: Peak Pulmonary Artery Systolic Pressure</measure>
    <time_frame>up to 72 hours post op</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-Operative Well Being: Peak Pulmonary Artery Diastolic Pressure</measure>
    <time_frame>up to 72 hours post op</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-Operative Well Being: Duration of Inotrope Need</measure>
    <time_frame>up to 72 hours post op</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-Operative Well Being: Duration of Vasopressor</measure>
    <time_frame>up to 72 hours post op</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-Operative Well Being: Total Dose of Vasopressor</measure>
    <time_frame>up to 72 hours post op</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-Operative Well Being: Daily Crystalloid Volume</measure>
    <time_frame>up to 72 hours post op</time_frame>
    <description>for 0-24h, 24-48h and 48-72h; total volume balance at 72-hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-Operative Well Being: Daily Blood Product Transfusion Volume</measure>
    <time_frame>up to 72 hours post op</time_frame>
    <description>for 0-24h, 24-48h and 48-72h; total volume balance at 72-hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-Operative Well Being: Daily Chest Tube Output Volume</measure>
    <time_frame>up to 72 hours post op</time_frame>
    <description>for 0-24h, 24-48h and 48-72h; total volume balance at 72-hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-Operative Well Being: Duration of Post-Operative Mechanical Ventilation</measure>
    <time_frame>up to Post Operative Day 7</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-Operative Well Being: PaO2 / FIO2 ratios</measure>
    <time_frame>Post Operative Day 1, Post Operative Day 2, Post Operative Day 3</time_frame>
    <description>The PF Ratio assesses the lungs' ability to oxygenate the blood. It is defined as the ratio of the partial pressure of oxygen in the arteries (PaO2 in mmHg) to the fractional inspired oxygen content from the ventilator (FiO2 in %).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-Operative Well Being: Time to Clearance of Lactate</measure>
    <time_frame>up to Post Operative Day 3</time_frame>
    <description>&quot;Clearance&quot; is defined as a lactate &lt;1 mmol/L.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Primary Graft Dysfunction</condition>
  <condition>Lung Transplant; Complications</condition>
  <arm_group>
    <arm_group_label>Vitamin C Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ascorbic Acid will be administered at a dose of 1500 mg in 100 mL of saline over 30 minutes intravenously once every 6 hours for a total of 72 hours</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin C</intervention_name>
    <description>Vitamin C is a first-line antioxidant that directly scavenges free radicals, inhibits reactive oxygen species (ROS) producing enzymes and recovers other cellular antioxidants</description>
    <arm_group_label>Vitamin C Arm</arm_group_label>
    <other_name>ascorbic acid</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant is scheduled for lung transplantation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-English speaking&#xD;
&#xD;
          -  Subject is known or believed to be pregnant&#xD;
&#xD;
          -  Subject is a prisoner.&#xD;
&#xD;
          -  Subject has impaired decision-making capacity.&#xD;
&#xD;
          -  Subject has known allergy to vitamin C.&#xD;
&#xD;
          -  Subject has history of nephrolithiasis, oxalosis or hyperoxaluria. (Cystic Fibrosis&#xD;
             patients are at risk of occult oxalosis / hyperoxaluria, therefore they will also be&#xD;
             excluded from the study.)&#xD;
&#xD;
          -  Glucose-6-phosphate dehydrogenase (G6PD) deficiency&#xD;
&#xD;
          -  Sickle cell anemia&#xD;
&#xD;
          -  Heredity hemochromatosis&#xD;
&#xD;
          -  Baseline creatinine &gt;2 mg/dL or any current kidney injury&#xD;
&#xD;
          -  Weight &lt;60 kg&#xD;
&#xD;
          -  Vitamin C supplement use or administration (including HAT therapy) within the last&#xD;
             month prior to transplantation&#xD;
&#xD;
          -  Current enrolment in another research study&#xD;
&#xD;
          -  Not suitable for study participation due to other reasons at the discretion of the&#xD;
             investigators.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Micah Long, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UW School of Medicine and Public Health</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>August 5, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2020</study_first_posted>
  <last_update_submitted>April 27, 2023</last_update_submitted>
  <last_update_submitted_qc>April 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Vitamin C</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Primary Graft Dysfunction</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>Yes</sharing_ipd>
    <ipd_description>Data from this study may be requested from other researchers up to 7 years after the completion of the primary endpoint by contacting Dr. Micah Long, the Principal Investigator of this study.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>up to 7 years after the completion of the primary endpoint</ipd_time_frame>
  </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/NCT04505878
org study id: 2020-0503
secondary id: A530900
secondary id: SMPH/ANESTHESIOLOGY
secondary id: Protocol Version 0.05
nct id: NCT04505878
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study is being done to determine if parenterally administered ascorbic acid (Vitamin C)
      given at the time of lung transplant is safe. Vitamin C may be an effective intervention
      towards primary graft dysfunction (PGD). The study will enroll 69 participants who consent to
      the intervention. Participants who do not consent to the intervention will be treated
      according to standard-of-care, but may choose to be consented to have their data
      retrospectively reviewed. Based on our consent rate, this group may include 40-70
      participants. Participants will be on study for up to 12 months.
PGD is a frequent and severe outcome that impacts both short- and long-term outcomes after
      lung transplantation. Major pathophysiologic contributors include ischemia and reperfusion
      injury, mitochondrial dysfunction and endothelial failure. No directed therapy exists.
      Vitamin C is a first-line antioxidant that also acts at the endothelium and mitochondria to
      decrease permeability and leak, inhibit mitochondrial dysfunction and improve ischemia and
      reperfusion. When combined with steroids, part of standard care for lung transplant
      recipients, these effects may be enhanced and synergistically inhibit instigators of patient
      injury. A pilot trial will ensure safety of this potential intervention and guide future
      research into this important outcome measure. It will be readily received in the literature.

      For the present study, vitamin C will be administered parenterally at a dose of 1,500 mg
      every 6 hours, a dose that is widely accepted and used in other clinical contexts where the
      drug is studied, such as sepsis. This will predictably reconstitute levels and achieve
      supratherapeutic benefit towards oxidant scavenging, while avoiding the potential pro-oxidant
      effects seen at exceedingly high doses. To this end, the investigators will exclude patients
      where the standard dosing of vitamin C will exceed 100 mg/kg/day (excluding patients <60 kg).
      Dosing will continue through post-operative day (POD) 3 to effectively assess for the impact
      of vitamin C on PGD.

      Primary Objectives

        -  To assess whether parenterally administered ascorbic acid (vitamin C) is safe in the
           lung transplant population

        -  To estimate adherence to ascorbic acid administration protocol in this study population
           and to identify obstacles to feasibility of future trials using this protocol

      Secondary Objectives

        -  To assess whether parenterally administered ascorbic acid (vitamin C) may decrease the
           rate and severity of PGD after lung transplant

        -  To establish the incidence of vitamin C and vitamin B1 (thiamine) deficiencies in the
           lung transplant population, and the responsiveness of vitamin C levels to our selected
           parenteral therapy

        -  To identify interventions that will optimize the post-operative wellbeing of patients
           receiving lung transplants by decreasing primary graft dysfunction (short and
           intermediate-to-long term

      Stop Criteria

        -  Anuria x 3-hours

        -  Moderate, Grade 2 AKI (doubling of baseline creatinine)

        -  An acute, unexplained hemoglobin drop of >2 mg/dL
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This is a pilot single-arm unblinded trial to assess whether parenterally administered ascorbic acid (vitamin C) is safe in the lung transplant population.The investigators will not randomize or control; a retrospective cohort of participants not treated with vitamin C will be reviewed from 2015-2020. Those participants who decline the intervention will have the choice to consent to having their data be considered as part of the (non-retrospective) controls and be considered in our statistical analysis for outcomes, including analysis between this group and the historical controls. All participants who consent will be administered the therapy and participants will be evaluated via an intention-to-treat analysis.
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence and Severity of Kidney Injury Post Operative Day (POD) 1
time frame: Post Operative Day 1
description: The primary endpoint is the safety of the vitamin C intervention. This will be measured by the incidence and severity of kidney injuries on POD 1, POD 2, POD 3, POD 4, and POD 7. Acute kidney injury (AKI) is defined as any creatinine (Cr) that is 1.5-times the participant's baseline / immediate preoperative creatinine. Severity escalates with increasing ratios: Mild, stage 1 AKI (Cr 1.5-1.99x baseline); Moderate, stage 2 AKI (Cr 2-2.9x baseline); and Severe, stage 3 AKI (Cr >3x baseline or any initiation of dialysis).
measure: Incidence and Severity of Kidney Injury POD 2
time frame: Post Operative Day 2
description: The primary endpoint is the safety of the vitamin C intervention. This will be measured by the incidence and severity of kidney injuries on POD 1, POD 2, POD 3, POD 4, and POD 7. Acute kidney injury (AKI) is defined as any creatinine (Cr) that is 1.5-times the participant's baseline / immediate preoperative creatinine. Severity escalates with increasing ratios: Mild, stage 1 AKI (Cr 1.5-1.99x baseline); Moderate, stage 2 AKI (Cr 2-2.9x baseline); and Severe, stage 3 AKI (Cr >3x baseline or any initiation of dialysis).
measure: Incidence and Severity of Kidney Injury POD 3
time frame: Post Operative Day 3
description: The primary endpoint is the safety of the vitamin C intervention. This will be measured by the incidence and severity of kidney injuries on POD 1, POD 2, POD 3, POD 4, and POD 7. Acute kidney injury (AKI) is defined as any creatinine (Cr) that is 1.5-times the participant's baseline / immediate preoperative creatinine. Severity escalates with increasing ratios: Mild, stage 1 AKI (Cr 1.5-1.99x baseline); Moderate, stage 2 AKI (Cr 2-2.9x baseline); and Severe, stage 3 AKI (Cr >3x baseline or any initiation of dialysis).
measure: Incidence and Severity of Kidney Injury POD 4
time frame: Post Operative Day 4
description: The primary endpoint is the safety of the vitamin C intervention. This will be measured by the incidence and severity of kidney injuries on POD 1, POD 2, POD 3, POD 4, and POD 7. Acute kidney injury (AKI) is defined as any creatinine (Cr) that is 1.5-times the participant's baseline / immediate preoperative creatinine. Severity escalates with increasing ratios: Mild, stage 1 AKI (Cr 1.5-1.99x baseline); Moderate, stage 2 AKI (Cr 2-2.9x baseline); and Severe, stage 3 AKI (Cr >3x baseline or any initiation of dialysis).
measure: Incidence and Severity of Kidney Injury POD 7
time frame: Post Operative Day 7
description: The primary endpoint is the safety of the vitamin C intervention. This will be measured by the incidence and severity of kidney injuries on POD 1, POD 2, POD 3, POD 4, and POD 7. Acute kidney injury (AKI) is defined as any creatinine (Cr) that is 1.5-times the participant's baseline / immediate preoperative creatinine. Severity escalates with increasing ratios: Mild, stage 1 AKI (Cr 1.5-1.99x baseline); Moderate, stage 2 AKI (Cr 2-2.9x baseline); and Severe, stage 3 AKI (Cr >3x baseline or any initiation of dialysis).
measure: Incidence of New Dialysis Initiation
time frame: up to Post Operative Day 7
measure: Participant Vitamin C Levels
time frame: Baseline, Post Operative Day 1, Post Operative Day 2, Post Operative Day 3
measure: Participant Thiamine Levels
time frame: Baseline, Post Operative Day 1, Post Operative Day 2, Post Operative Day 3
measure: Incidence of Primary Graft Dysfunction (PGD)
time frame: up to Post Operative Day 7
description: Primary Graft Dysfunction is defined as chest x-ray (CXR)-infiltrates with or without depressed oxygenation function, assessed by the "PF-Ratio," which is the PaO2 / FiO2.
measure: Incidence and Severity of PGD on POD 3
time frame: Post Operative Day 3
description: Primary Graft Dysfunction is defined as chest x-ray (CXR)-infiltrates with or without depressed oxygenation function, assessed by the "PF-Ratio," which is the PaO2 / FiO2. Severity is defined as: PGD Grade 1 = CXR findings and any PF Ratio > 300; PGD Grade 2 = CXR findings and PF Ratio 200-300; and PGD Grade 3 = CXR findings and PF Ratio <200.
measure: Tacrolimus Levels
time frame: Post Operative Days 2, 3, 4, and 7
measure: Tacrolimus Doses
time frame: Post Operative Days 4 and 7
measure: Post-Operative Well Being: Mortality
time frame: at Post Operative Day 30 and Post Operative Day 90 via chart review
measure: Post-Operative Well Being: Atrial Fibrillation
time frame: up to Post Operative Day 7
measure: Post-Operative Well Being: ICU Length of Stay
time frame: up to Post Operative Day 30 (chart review)
measure: Post-Operative Well Being: Hospital Length of Stay
time frame: up to Post Operative Day 90 (chart review)
measure: Post-Operative Well Being: Nadir Cardiac Index
time frame: up to 72 hours post op
measure: Post-Operative Well Being: Peak Pulmonary Artery Systolic Pressure
time frame: up to 72 hours post op
measure: Post-Operative Well Being: Peak Pulmonary Artery Diastolic Pressure
time frame: up to 72 hours post op
measure: Post-Operative Well Being: Duration of Inotrope Need
time frame: up to 72 hours post op
measure: Post-Operative Well Being: Duration of Vasopressor
time frame: up to 72 hours post op
measure: Post-Operative Well Being: Total Dose of Vasopressor
time frame: up to 72 hours post op
measure: Post-Operative Well Being: Daily Crystalloid Volume
time frame: up to 72 hours post op
description: for 0-24h, 24-48h and 48-72h; total volume balance at 72-hours
measure: Post-Operative Well Being: Daily Blood Product Transfusion Volume
time frame: up to 72 hours post op
description: for 0-24h, 24-48h and 48-72h; total volume balance at 72-hours
measure: Post-Operative Well Being: Daily Chest Tube Output Volume
time frame: up to 72 hours post op
description: for 0-24h, 24-48h and 48-72h; total volume balance at 72-hours
measure: Post-Operative Well Being: Duration of Post-Operative Mechanical Ventilation
time frame: up to Post Operative Day 7
measure: Post-Operative Well Being: PaO2 / FIO2 ratios
time frame: Post Operative Day 1, Post Operative Day 2, Post Operative Day 3
description: The PF Ratio assesses the lungs' ability to oxygenate the blood. It is defined as the ratio of the partial pressure of oxygen in the arteries (PaO2 in mmHg) to the fractional inspired oxygen content from the ventilator (FiO2 in %).
measure: Post-Operative Well Being: Time to Clearance of Lactate
time frame: up to Post Operative Day 3
description: "Clearance" is defined as a lactate <1 mmol/L.
arm group label: Vitamin C Arm
arm group type: Experimental
description: Ascorbic Acid will be administered at a dose of 1500 mg in 100 mL of saline over 30 minutes intravenously once every 6 hours for a total of 72 hours
intervention type: Drug
intervention name: Vitamin C
description: Vitamin C is a first-line antioxidant that directly scavenges free radicals, inhibits reactive oxygen species (ROS) producing enzymes and recovers other cellular antioxidants
arm group label: Vitamin C Arm
other name: ascorbic acid
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Micah Long, MD
role: Principal Investigator
affiliation: UW School of Medicine and Public Health
country: United States
responsible party type: Sponsor
mesh term: Primary Graft Dysfunction
mesh term: Ascorbic Acid
sharing ipd: Yes
ipd description: Data from this study may be requested from other researchers up to 7 years after the completion of the primary endpoint by contacting Dr. Micah Long, the Principal Investigator of this study.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: up to 7 years after the completion of the primary endpoint