<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/NCT03756727</url>
  </required_header>
  <id_info>
    <org_study_id>XYFY-2018-1101</org_study_id>
    <nct_id>NCT03756727</nct_id>
  </id_info>
  <brief_title>Effect of Ascorbic Acid on Postoperative Pulmonary Complications in Patients Undergoing Cardiac Surgery</brief_title>
  <official_title>Effect of Perioperative Application of Ascorbic Acid on Postoperative Pulmonary Complications in Patients Undergoing Cardiac Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Xuzhou Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Xuzhou Medical University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Postoperative pulmonary complications(PPCs) including, but not limited to ,hypoxemia,&#xD;
      pneumonia, ventilator-induced lung injury, and acute respiratory distress syndrome&#xD;
      (ARDS),atelectasis,pleural effusion .PPCs may result in increased resources utilization,&#xD;
      delayed mobilization, prolonged need of supplemental oxygen or mechanical ventilation,and a&#xD;
      longer hospital stay.postoperative pulmonary complications are common after cardiac surgery,&#xD;
      often increasing postoperative morbidity and mortality.The extracorporeal&#xD;
      circulation,increased oxygen concentration inhaled and the development of massive atelectasis&#xD;
      after open-chest surgery commonly activate lung inflammation, amplifying the harm Injury of&#xD;
      pulmonary .Currently, plenty of interventions have been studied to prevent PPCs after&#xD;
      surgery. Most of the recent research has focused on physical therapy such as lung-protective&#xD;
      modes during intraoperative mechanical ventilation, Alveolar Recruitment, and respiratory&#xD;
      muscle training.These therapies have a certain effect, but still not satisfactory.Ascorbic&#xD;
      acid is an important cofactor in multiple enzymatic reactions where its main function is as a&#xD;
      reducing agent.Studies have shown that ascorbic acid can reduce both ischemia-reperfusion&#xD;
      injury and oxidative stress. Unfortunately, no studies examined whether Ascorbic acid can&#xD;
      reduce PPCs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The possible mechanisms of ascorbic acid to alleviate ischemia-reperfusion injury are as&#xD;
      follows: 1 Ascorbic acid as a first-line antioxidant in plasma can reduce stress by&#xD;
      eliminating excess Reactive oxygen species and reduce damage. 2 provides rapid electron&#xD;
      transfer to react with superoxide and hydroxyl group to scavenge reactive oxygen released&#xD;
      into the circulation. 3 Ascorbic acid can reduce lipid peroxidation and reduce lung injury&#xD;
      caused by ischemia-reperfusion by scavenging oxygen free radicals. 4 Vitamin C can promote&#xD;
      the production of cytokines by immune cells to reduce local inflammatory reactions and&#xD;
      improve tissue microcirculation.The study aims to explore whether daily used Ascorbic acid in&#xD;
      the perioperative period has a preventive effect on PPCs in patients undergoing cardiac&#xD;
      surgery, and through short-term and long-term follow-up, to investigate the effect on&#xD;
      post-hospitalization Prognosis .&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">December 1, 2018</start_date>
  <completion_date type="Anticipated">July 2019</completion_date>
  <primary_completion_date type="Anticipated">May 30, 2019</primary_completion_date>
  <phase>Early Phase 1</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>Prevention</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>severity of postoperative pulmonary complications</measure>
    <time_frame>an average of 2 weeks</time_frame>
    <description>Use the postoperative pulmonary complications score to record the severity. scored ranging from 0 to 5.Scored the severity once a day, record the highest score.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>incidence of postoperative pulmonary complications</measure>
    <time_frame>an average of 10 days</time_frame>
    <description>incidence of postoperative pulmonary complications during hospital stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>length of ICU stay and length of hospital stay</measure>
    <time_frame>an average of 10 days</time_frame>
    <description>all patients transfer to ICU after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>extubation and wake time</measure>
    <time_frame>an average of 1 day</time_frame>
    <description>length of extubation time,length of wake time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PaO2/FiO2</measure>
    <time_frame>1 day, 3 days,5 days post surgery</time_frame>
    <description>Oxygenation index (PaO2/FiO2) in millimeter mercury column.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>A-aDO2</measure>
    <time_frame>1 day, 3 days,5 days post surgery</time_frame>
    <description>alveolar-arterial oxygen tension difference (A-aDO2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plateau pressure</measure>
    <time_frame>an average of 1 day</time_frame>
    <description>Plateau pressure in centimeter water column</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak airway pressure</measure>
    <time_frame>an average of 1 day</time_frame>
    <description>Peak airway pressure in centimeter water column</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>positive end expiratory pressure</measure>
    <time_frame>an average of 1 day</time_frame>
    <description>positive end expiratory pressure in centimeter water column</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>lung compliance</measure>
    <time_frame>an average of 1 day</time_frame>
    <description>lung compliance in Milliliter/ centimeter water column</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>post-hospitalization follow-up</measure>
    <time_frame>once a day till 30 days post-hospitalization</time_frame>
    <description>record the incidence of postoperative pulmonary complications after hospital discharged.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">110</enrollment>
  <condition>Postoperative Pulmonary Complications</condition>
  <arm_group>
    <arm_group_label>Ascorbic acid group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>the patients received 2g of intravenous Ascorbic acid at the night before surgery, during the surgery and five days after surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control comparator group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>the patients received 10ml saline at the night before surgery, during the surgery and five days after surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ascorbic Acid</intervention_name>
    <description>Patients in Ascorbic acid group received 2g of intravenous Ascorbic acid at the night before surgery, during the surgery and five days after surgery (once a day).</description>
    <arm_group_label>Ascorbic acid group</arm_group_label>
    <other_name>Vitamin c</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>Patients in Control Comparator group received saline 10ml at the night before surgery, during the surgery and five days after surgery (once a day).</description>
    <arm_group_label>Control comparator group</arm_group_label>
    <other_name>Saline Solution</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age between 18-60 years old&#xD;
&#xD;
          2. Selective cardiac surgery under cardiopulmonary bypass&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Emergency surgery&#xD;
&#xD;
          2. Previous cardiac surgery&#xD;
&#xD;
          3. Severe lung disease&#xD;
&#xD;
          4. BMI&lt;18 or &gt;30&#xD;
&#xD;
          5. Mean pulmonary arterial pressure &gt;40 mmHg&#xD;
&#xD;
          6. were allergic to ascorbic acid&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jin Dong Liu, M.S</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Affiliated Hospital of Xuzhou Medical University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jin Dong Liu, M.S</last_name>
    <phone>+86-13951355136</phone>
    <email>liujindong1818@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Dongyue Wang</last_name>
    <phone>+86-15996931208</phone>
    <email>763996674@qq.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The Affiliated Hospital of Xuzhou Medical University</name>
      <address>
        <city>Xuzhou</city>
        <state>Jiangsu</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Mazo V, Sabate S, Canet J, Gallart L, de Abreu MG, Belda J, Langeron O, Hoeft A, Pelosi P. Prospective external validation of a predictive score for postoperative pulmonary complications. Anesthesiology. 2014 Aug;121(2):219-31. doi: 10.1097/ALN.0000000000000334.</citation>
    <PMID>24901240</PMID>
  </reference>
  <reference>
    <citation>Baker WL, Coleman CI. Meta-analysis of ascorbic acid for prevention of postoperative atrial fibrillation after cardiac surgery. Am J Health Syst Pharm. 2016 Dec 15;73(24):2056-2066. doi: 10.2146/ajhp160066. Epub 2016 Nov 2.</citation>
    <PMID>27806938</PMID>
  </reference>
  <reference>
    <citation>Costa Leme A, Hajjar LA, Volpe MS, Fukushima JT, De Santis Santiago RR, Osawa EA, Pinheiro de Almeida J, Gerent AM, Franco RA, Zanetti Feltrim MI, Nozawa E, de Moraes Coimbra VR, de Moraes Ianotti R, Hashizume CS, Kalil Filho R, Auler JO Jr, Jatene FB, Gomes Galas FR, Amato MB. Effect of Intensive vs Moderate Alveolar Recruitment Strategies Added to Lung-Protective Ventilation on Postoperative Pulmonary Complications: A Randomized Clinical Trial. JAMA. 2017 Apr 11;317(14):1422-1432. doi: 10.1001/jama.2017.2297.</citation>
    <PMID>28322416</PMID>
  </reference>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 25, 2018</study_first_submitted>
  <study_first_submitted_qc>November 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <last_update_submitted>November 27, 2018</last_update_submitted>
  <last_update_submitted_qc>November 27, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 28, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Xuzhou Medical University</investigator_affiliation>
    <investigator_full_name>Jin Dong Liu</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ascorbic Acid</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Individual Participant Data(IPD) will be available when this trial is finished and the article have been published</ipd_description>
  </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/NCT03756727
org study id: XYFY-2018-1101
nct id: NCT03756727
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Postoperative pulmonary complications(PPCs) including, but not limited to ,hypoxemia,
      pneumonia, ventilator-induced lung injury, and acute respiratory distress syndrome
      (ARDS),atelectasis,pleural effusion .PPCs may result in increased resources utilization,
      delayed mobilization, prolonged need of supplemental oxygen or mechanical ventilation,and a
      longer hospital stay.postoperative pulmonary complications are common after cardiac surgery,
      often increasing postoperative morbidity and mortality.The extracorporeal
      circulation,increased oxygen concentration inhaled and the development of massive atelectasis
      after open-chest surgery commonly activate lung inflammation, amplifying the harm Injury of
      pulmonary .Currently, plenty of interventions have been studied to prevent PPCs after
      surgery. Most of the recent research has focused on physical therapy such as lung-protective
      modes during intraoperative mechanical ventilation, Alveolar Recruitment, and respiratory
      muscle training.These therapies have a certain effect, but still not satisfactory.Ascorbic
      acid is an important cofactor in multiple enzymatic reactions where its main function is as a
      reducing agent.Studies have shown that ascorbic acid can reduce both ischemia-reperfusion
      injury and oxidative stress. Unfortunately, no studies examined whether Ascorbic acid can
      reduce PPCs.
The possible mechanisms of ascorbic acid to alleviate ischemia-reperfusion injury are as
      follows: 1 Ascorbic acid as a first-line antioxidant in plasma can reduce stress by
      eliminating excess Reactive oxygen species and reduce damage. 2 provides rapid electron
      transfer to react with superoxide and hydroxyl group to scavenge reactive oxygen released
      into the circulation. 3 Ascorbic acid can reduce lipid peroxidation and reduce lung injury
      caused by ischemia-reperfusion by scavenging oxygen free radicals. 4 Vitamin C can promote
      the production of cytokines by immune cells to reduce local inflammatory reactions and
      improve tissue microcirculation.The study aims to explore whether daily used Ascorbic acid in
      the perioperative period has a preventive effect on PPCs in patients undergoing cardiac
      surgery, and through short-term and long-term follow-up, to investigate the effect on
      post-hospitalization Prognosis .
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: severity of postoperative pulmonary complications
time frame: an average of 2 weeks
description: Use the postoperative pulmonary complications score to record the severity. scored ranging from 0 to 5.Scored the severity once a day, record the highest score.
measure: incidence of postoperative pulmonary complications
time frame: an average of 10 days
description: incidence of postoperative pulmonary complications during hospital stay
measure: length of ICU stay and length of hospital stay
time frame: an average of 10 days
description: all patients transfer to ICU after surgery
measure: extubation and wake time
time frame: an average of 1 day
description: length of extubation time,length of wake time
measure: PaO2/FiO2
time frame: 1 day, 3 days,5 days post surgery
description: Oxygenation index (PaO2/FiO2) in millimeter mercury column.
measure: A-aDO2
time frame: 1 day, 3 days,5 days post surgery
description: alveolar-arterial oxygen tension difference (A-aDO2)
measure: Plateau pressure
time frame: an average of 1 day
description: Plateau pressure in centimeter water column
measure: Peak airway pressure
time frame: an average of 1 day
description: Peak airway pressure in centimeter water column
measure: positive end expiratory pressure
time frame: an average of 1 day
description: positive end expiratory pressure in centimeter water column
measure: lung compliance
time frame: an average of 1 day
description: lung compliance in Milliliter/ centimeter water column
measure: post-hospitalization follow-up
time frame: once a day till 30 days post-hospitalization
description: record the incidence of postoperative pulmonary complications after hospital discharged.
arm group label: Ascorbic acid group
arm group type: Experimental
description: the patients received 2g of intravenous Ascorbic acid at the night before surgery, during the surgery and five days after surgery.
arm group label: Control comparator group
arm group type: Placebo Comparator
description: the patients received 10ml saline at the night before surgery, during the surgery and five days after surgery.
intervention type: Drug
intervention name: Ascorbic Acid
description: Patients in Ascorbic acid group received 2g of intravenous Ascorbic acid at the night before surgery, during the surgery and five days after surgery (once a day).
arm group label: Ascorbic acid group
other name: Vitamin c
intervention type: Drug
intervention name: Saline
description: Patients in Control Comparator group received saline 10ml at the night before surgery, during the surgery and five days after surgery (once a day).
arm group label: Control comparator group
other name: Saline Solution
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Jin Dong Liu, M.S
role: Principal Investigator
affiliation: The Affiliated Hospital of Xuzhou Medical University
last name: Jin Dong Liu, M.S
phone: +86-13951355136
email: liujindong1818@163.com
last name: Dongyue Wang
phone: +86-15996931208
email: 763996674@qq.com
facility: 
country: China
citation: Mazo V, Sabate S, Canet J, Gallart L, de Abreu MG, Belda J, Langeron O, Hoeft A, Pelosi P. Prospective external validation of a predictive score for postoperative pulmonary complications. Anesthesiology. 2014 Aug;121(2):219-31. doi: 10.1097/ALN.0000000000000334.
PMID: 24901240
citation: Baker WL, Coleman CI. Meta-analysis of ascorbic acid for prevention of postoperative atrial fibrillation after cardiac surgery. Am J Health Syst Pharm. 2016 Dec 15;73(24):2056-2066. doi: 10.2146/ajhp160066. Epub 2016 Nov 2.
PMID: 27806938
citation: Costa Leme A, Hajjar LA, Volpe MS, Fukushima JT, De Santis Santiago RR, Osawa EA, Pinheiro de Almeida J, Gerent AM, Franco RA, Zanetti Feltrim MI, Nozawa E, de Moraes Coimbra VR, de Moraes Ianotti R, Hashizume CS, Kalil Filho R, Auler JO Jr, Jatene FB, Gomes Galas FR, Amato MB. Effect of Intensive vs Moderate Alveolar Recruitment Strategies Added to Lung-Protective Ventilation on Postoperative Pulmonary Complications: A Randomized Clinical Trial. JAMA. 2017 Apr 11;317(14):1422-1432. doi: 10.1001/jama.2017.2297.
PMID: 28322416
responsible party type: Principal Investigator
investigator affiliation: Xuzhou Medical University
investigator full name: Jin Dong Liu
investigator title: Principal Investigator
mesh term: Ascorbic Acid
sharing ipd: Undecided
ipd description: Individual Participant Data(IPD) will be available when this trial is finished and the article have been published