<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/NCT04420897</url>
  </required_header>
  <id_info>
    <org_study_id>The effect of Pa02 in KT</org_study_id>
    <nct_id>NCT04420897</nct_id>
  </id_info>
  <brief_title>The Effect of Intraoperative Arterial Oxygen Pressures on Early Post-Operative Patient and Graft Survival in Living Donor Kidney Transplantation</brief_title>
  <official_title>The Effect of Intraoperative Arterial Oxygen Pressures on Early Post-Operative Patient and Graft Survival in Living Donor Kidney Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Akdeniz University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Akdeniz University</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>
      We evaluated the prognostic role of the intraoperative arterial oxygen partial pressures&#xD;
      (PaO2) on postoperative patient and graft survival in living donor kidney transplantations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Undoubtedly, one of the most important elements of life on earth is oxygen. Aerobic organisms&#xD;
      adapted to the 20.8% oxygen ratio in the atmosphere have survived even lower than this&#xD;
      concentration by developing various defense mechanisms. The real question is whether high&#xD;
      levels of oxygen in the blood, which are administered iatrogenically, leads to tissue&#xD;
      destruction.&#xD;
&#xD;
      Reactive Oxygen Species (ROS), which is a result of hyperoxia and may be useful even at low&#xD;
      levels, may cause tissue loss due to oxidative stress, also called oxygen-free radicals. ROS,&#xD;
      whose toxicity is very destructive with its accumulation, may cause damage to macromolecular&#xD;
      structures such as lipids, protein, mitochondrial and nuclear DNA. On the organs of the&#xD;
      exposed oxidative stress; For lung, asthma, chronic obstructive pulmonary disease (COPD),&#xD;
      acute respiratory distress syndrome (ARDS), cardiovascular system, ischemic heart disease&#xD;
      (IHD), hypertension, shock, heart failure, while kidney failure and glomerulonephritis can&#xD;
      cause unwanted complications.&#xD;
&#xD;
      The kidneys get for circulation, only 20% of the cardiac output. Since the arterial and&#xD;
      venous (AV) structures in the kidneys are anatomically parallel to each other, the oxygen&#xD;
      concentration in the renal vein may be relatively higher than the efferent arteriole and&#xD;
      cortex because of the oxygen shunt. Thanks to this mechanism, in clinical situations where&#xD;
      partial oxygen pressure (Pa02) is high, the oxygen concentration presented to the kidney&#xD;
      tissues remains within a certain limit. In fact, AV shunt protects kidney tissue with a&#xD;
      structural antioxidant mechanism. Thus, the increase in renal blood flow (RBF) will cause an&#xD;
      increase in AV oxygen shunt in parallel, the blood coming to the kidneys participates in the&#xD;
      systemic circulation without entering the renal microcirculation. It has been suggested that&#xD;
      shunt occurs to protect from hyperoxia at the tissue level by decreasing blood volume in the&#xD;
      kidneys. Oxidative stress, which is inevitable as a result, will increase tissue hypoxia&#xD;
      paradoxically by increasing the oxygen consumption of the kidneys. It is stated that uremic&#xD;
      toxin, especially indoxyl sulfate (IS) accumulation is the cause of the mentioned table.&#xD;
      Apart from IS, phenyl sulfate and ρ-cresy sulfate make tubular cells susceptible by reducing&#xD;
      glutathione levels. Thus, increased renal hypoxia, renal oxidative stress will result in&#xD;
      renal inflammation and fibrosis.&#xD;
&#xD;
      According to recent studies, the antioxidant defense mechanism has been shown not only to be&#xD;
      limited to AV shunt. But also the dynamic regulation of intrarenal oxygenation in RBF&#xD;
      changes. However, mechanisms developed to prevent hyperoxia have made kidney tissue sensitive&#xD;
      to hypoxia. The increase in AV oxygen shunt causes an increase in tissue hypoxia.&#xD;
&#xD;
      Although endogenous antioxidant mechanisms play a major role against free radicals, the&#xD;
      postoperative effects of iatrogenic hyperoxia on transplanted kidney grafts and patient&#xD;
      survival remain a subject to be investigated. That's why we aim to understand the impact of&#xD;
      iatrogenic hyperoxia during the living donor kidney transplantation operations by&#xD;
      retrospective data analyzing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 1, 2020</start_date>
  <completion_date type="Actual">December 1, 2020</completion_date>
  <primary_completion_date type="Actual">November 29, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Assessment of arterial blood gases with normoxia</measure>
    <time_frame>Postoperative first following month</time_frame>
    <description>Approximately 1000 patients enrolled have living donor renal transplantation. After separation by study limitation of the accepted groups according to the PaO2 levels, graft functions and the patient's prognosis will be evaluated by enrolled data gained during the postoperative first month.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of arterial blood gases with Moderate hyperoxemia</measure>
    <time_frame>Postoperative first following month</time_frame>
    <description>Approximately 1000 patients enrolled have living donor renal transplantation. After separation by study limitation of the accepted groups according to the PaO2 levels, graft functions and the patient's prognosis will be evaluated by enrolled data gained during the postoperative first month.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of arterial blood gases with Severe hyperoxemia</measure>
    <time_frame>Postoperative first following month</time_frame>
    <description>Approximately 1000 patients enrolled have living donor renal transplantation. After separation by study limitation of the accepted groups according to the PaO2 levels, graft functions and the patient's prognosis will be evaluated by enrolled data gained during the postoperative first month.</description>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">247</enrollment>
  <condition>Kidney Transplant; Complications</condition>
  <condition>Hyperoxia</condition>
  <condition>Graft Dysfunction</condition>
  <arm_group>
    <arm_group_label>Normoxy: PaO2 = 80-120 mm Hg</arm_group_label>
    <description>Data collection explained below: Arterial blood samples from all groups shall be taken after induction, 5 minutes after graft perfusion, and end of surgery in the intraoperative period, in the operating room. The duration of the intensive care unit (ICU), the duration of mechanical ventilation in intensive care, Whether or not to re-intubate, hospital stay, intraoperative and postoperative laboratory data, immunosuppression regimen, postoperative complications (surgical site infection, ischemic vascular conditions, complications from respiratory) and interventions will be included for the study analysis. The survival of the patients will be enrolled, and the relationship between the obtained data and survival will be investigated. For early-stage graft survival, postoperatively; Data such as renal replacement therapy, the total amount of urine levels, creatinine values, presence of delayed graft function will be recorded.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Moderate hyperoxemia: PaO2 =120-200 mm Hg</arm_group_label>
    <description>Data collection explained below: Arterial blood samples from all groups shall be taken after induction, 5 minutes after graft perfusion, and end of surgery in the intraoperative period, in the operating room. The duration of the intensive care unit (ICU), the duration of mechanical ventilation in intensive care, Whether or not to re-intubate, hospital stay, intraoperative and postoperative laboratory data, immunosuppression regimen, postoperative complications (surgical site infection, ischemic vascular conditions, complications from respiratory) and interventions will be included for the study analysis. The survival of the patients will be enrolled, and the relationship between the obtained data and survival will be investigated. For early-stage graft survival, postoperatively; Data such as renal replacement therapy, the total amount of urine levels, creatinine values, presence of delayed graft function will be recorded.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Severe hyperoxemia: PaO2 &gt;200 mm Hg</arm_group_label>
    <description>Data collection explained below: Arterial blood samples from all groups shall be taken after induction, 5 minutes after graft perfusion, and end of surgery in the intraoperative period, in the operating room. The duration of the intensive care unit (ICU), the duration of mechanical ventilation in intensive care, Whether or not to re-intubate, hospital stay, intraoperative and postoperative laboratory data, immunosuppression regimen, postoperative complications (surgical site infection, ischemic vascular conditions, complications from respiratory) and interventions will be included for the study analysis. The survival of the patients will be enrolled, and the relationship between the obtained data and survival will be investigated. For early-stage graft survival, postoperatively; Data such as renal replacement therapy, the total amount of urine levels, creatinine values, presence of delayed graft function will be recorded.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Arterial blood gas samples</intervention_name>
    <description>Blood gases taken during the operation will be analyzed retrospectively. Whether these results have an effect on graft survival will be examined by reaching their records in the postoperative period.</description>
    <arm_group_label>Moderate hyperoxemia: PaO2 =120-200 mm Hg</arm_group_label>
    <arm_group_label>Normoxy: PaO2 = 80-120 mm Hg</arm_group_label>
    <arm_group_label>Severe hyperoxemia: PaO2 &gt;200 mm Hg</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        We enrolled only 1000 adult living donor kidney transplantations closed files started from&#xD;
        1st of January 2017 to 1st of November 2019. The study conducted at the Department of&#xD;
        Anesthesiology and Critical Care with the Department of General and Visceral Surgery&#xD;
        Medical Center. All recipient surgical procedure was carried out by the same specialized&#xD;
        transplantation surgeons and anesthesiologists after a positive vote of the local ethics&#xD;
        committee for transplantation. Recipients with a history of myocardial infarction, chronic&#xD;
        respiratory disease (bronchial asthma, COPD) were excluded from the study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients who had living donor kidney transplantation between January 2014 and June&#xD;
             2019 at Akdeniz University Faculty of Medicine Organ Transplant Center.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with missing data&#xD;
&#xD;
          -  Patients with a history of chronic heart failure or chronic respiratory disease&#xD;
             (bronchial asthma, COPD).&#xD;
&#xD;
          -  Presence of cadaveric donor kidney transplantation&#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_official>
    <last_name>Bora Di̇nc, MD, Assist. Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Akdeniz University Medical Faculty</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Akdeniz University Medical Faculty Department of Anesthesiology and Reanimation</name>
      <address>
        <city>Antalya</city>
        <zip>07059</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Turkey</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>December 1, 2020</last_update_submitted>
  <last_update_submitted_qc>December 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Akdeniz University</investigator_affiliation>
    <investigator_full_name>Bora Dinc</investigator_full_name>
    <investigator_title>Assistant Professor Department of Anesthesiology and Reanimation</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hyperoxia</mesh_term>
  </condition_browse>
  <!-- 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/NCT04420897
org study id: The effect of Pa02 in KT
nct id: NCT04420897
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
We evaluated the prognostic role of the intraoperative arterial oxygen partial pressures
      (PaO2) on postoperative patient and graft survival in living donor kidney transplantations.
Undoubtedly, one of the most important elements of life on earth is oxygen. Aerobic organisms
      adapted to the 20.8% oxygen ratio in the atmosphere have survived even lower than this
      concentration by developing various defense mechanisms. The real question is whether high
      levels of oxygen in the blood, which are administered iatrogenically, leads to tissue
      destruction.

      Reactive Oxygen Species (ROS), which is a result of hyperoxia and may be useful even at low
      levels, may cause tissue loss due to oxidative stress, also called oxygen-free radicals. ROS,
      whose toxicity is very destructive with its accumulation, may cause damage to macromolecular
      structures such as lipids, protein, mitochondrial and nuclear DNA. On the organs of the
      exposed oxidative stress; For lung, asthma, chronic obstructive pulmonary disease (COPD),
      acute respiratory distress syndrome (ARDS), cardiovascular system, ischemic heart disease
      (IHD), hypertension, shock, heart failure, while kidney failure and glomerulonephritis can
      cause unwanted complications.

      The kidneys get for circulation, only 20% of the cardiac output. Since the arterial and
      venous (AV) structures in the kidneys are anatomically parallel to each other, the oxygen
      concentration in the renal vein may be relatively higher than the efferent arteriole and
      cortex because of the oxygen shunt. Thanks to this mechanism, in clinical situations where
      partial oxygen pressure (Pa02) is high, the oxygen concentration presented to the kidney
      tissues remains within a certain limit. In fact, AV shunt protects kidney tissue with a
      structural antioxidant mechanism. Thus, the increase in renal blood flow (RBF) will cause an
      increase in AV oxygen shunt in parallel, the blood coming to the kidneys participates in the
      systemic circulation without entering the renal microcirculation. It has been suggested that
      shunt occurs to protect from hyperoxia at the tissue level by decreasing blood volume in the
      kidneys. Oxidative stress, which is inevitable as a result, will increase tissue hypoxia
      paradoxically by increasing the oxygen consumption of the kidneys. It is stated that uremic
      toxin, especially indoxyl sulfate (IS) accumulation is the cause of the mentioned table.
      Apart from IS, phenyl sulfate and ρ-cresy sulfate make tubular cells susceptible by reducing
      glutathione levels. Thus, increased renal hypoxia, renal oxidative stress will result in
      renal inflammation and fibrosis.

      According to recent studies, the antioxidant defense mechanism has been shown not only to be
      limited to AV shunt. But also the dynamic regulation of intrarenal oxygenation in RBF
      changes. However, mechanisms developed to prevent hyperoxia have made kidney tissue sensitive
      to hypoxia. The increase in AV oxygen shunt causes an increase in tissue hypoxia.

      Although endogenous antioxidant mechanisms play a major role against free radicals, the
      postoperative effects of iatrogenic hyperoxia on transplanted kidney grafts and patient
      survival remain a subject to be investigated. That's why we aim to understand the impact of
      iatrogenic hyperoxia during the living donor kidney transplantation operations by
      retrospective data analyzing.
observational model: Case-Control
time perspective: Retrospective
measure: Assessment of arterial blood gases with normoxia
time frame: Postoperative first following month
description: Approximately 1000 patients enrolled have living donor renal transplantation. After separation by study limitation of the accepted groups according to the PaO2 levels, graft functions and the patient's prognosis will be evaluated by enrolled data gained during the postoperative first month.
measure: Assessment of arterial blood gases with Moderate hyperoxemia
time frame: Postoperative first following month
description: Approximately 1000 patients enrolled have living donor renal transplantation. After separation by study limitation of the accepted groups according to the PaO2 levels, graft functions and the patient's prognosis will be evaluated by enrolled data gained during the postoperative first month.
measure: Assessment of arterial blood gases with Severe hyperoxemia
time frame: Postoperative first following month
description: Approximately 1000 patients enrolled have living donor renal transplantation. After separation by study limitation of the accepted groups according to the PaO2 levels, graft functions and the patient's prognosis will be evaluated by enrolled data gained during the postoperative first month.
arm group label: Normoxy: PaO2 = 80-120 mm Hg
description: Data collection explained below: Arterial blood samples from all groups shall be taken after induction, 5 minutes after graft perfusion, and end of surgery in the intraoperative period, in the operating room. The duration of the intensive care unit (ICU), the duration of mechanical ventilation in intensive care, Whether or not to re-intubate, hospital stay, intraoperative and postoperative laboratory data, immunosuppression regimen, postoperative complications (surgical site infection, ischemic vascular conditions, complications from respiratory) and interventions will be included for the study analysis. The survival of the patients will be enrolled, and the relationship between the obtained data and survival will be investigated. For early-stage graft survival, postoperatively; Data such as renal replacement therapy, the total amount of urine levels, creatinine values, presence of delayed graft function will be recorded.
arm group label: Moderate hyperoxemia: PaO2 =120-200 mm Hg
description: Data collection explained below: Arterial blood samples from all groups shall be taken after induction, 5 minutes after graft perfusion, and end of surgery in the intraoperative period, in the operating room. The duration of the intensive care unit (ICU), the duration of mechanical ventilation in intensive care, Whether or not to re-intubate, hospital stay, intraoperative and postoperative laboratory data, immunosuppression regimen, postoperative complications (surgical site infection, ischemic vascular conditions, complications from respiratory) and interventions will be included for the study analysis. The survival of the patients will be enrolled, and the relationship between the obtained data and survival will be investigated. For early-stage graft survival, postoperatively; Data such as renal replacement therapy, the total amount of urine levels, creatinine values, presence of delayed graft function will be recorded.
arm group label: Severe hyperoxemia: PaO2 >200 mm Hg
description: Data collection explained below: Arterial blood samples from all groups shall be taken after induction, 5 minutes after graft perfusion, and end of surgery in the intraoperative period, in the operating room. The duration of the intensive care unit (ICU), the duration of mechanical ventilation in intensive care, Whether or not to re-intubate, hospital stay, intraoperative and postoperative laboratory data, immunosuppression regimen, postoperative complications (surgical site infection, ischemic vascular conditions, complications from respiratory) and interventions will be included for the study analysis. The survival of the patients will be enrolled, and the relationship between the obtained data and survival will be investigated. For early-stage graft survival, postoperatively; Data such as renal replacement therapy, the total amount of urine levels, creatinine values, presence of delayed graft function will be recorded.
intervention type: Procedure
intervention name: Arterial blood gas samples
description: Blood gases taken during the operation will be analyzed retrospectively. Whether these results have an effect on graft survival will be examined by reaching their records in the postoperative period.
arm group label: Moderate hyperoxemia: PaO2 =120-200 mm Hg
arm group label: Normoxy: PaO2 = 80-120 mm Hg
arm group label: Severe hyperoxemia: PaO2 >200 mm Hg
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Bora Di̇nc, MD, Assist. Prof.
role: Principal Investigator
affiliation: Akdeniz University Medical Faculty
facility: 
country: Turkey
responsible party type: Principal Investigator
investigator affiliation: Akdeniz University
investigator full name: Bora Dinc
investigator title: Assistant Professor Department of Anesthesiology and Reanimation
mesh term: Hyperoxia