<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/NCT04450095</url>
  </required_header>
  <id_info>
    <org_study_id>0048-18-BNZ</org_study_id>
    <nct_id>NCT04450095</nct_id>
  </id_info>
  <brief_title>Effects of Endothelin Receptor Antagonist on Ischemic Kidney Injury During Nephron Sparing Surgery</brief_title>
  <official_title>Effects of Endothelin Receptor Antagonist on Ischemic Kidney Injury During Nephron Sparing Surgery for Renal Mass Excision: Assessment by Ischemia Biomarkers, NGAL, KIM-1</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bnai Zion Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Rambam Health Care Campus</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Bnai Zion Medical Center</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Based on animal studies, it was found that administration of endothelial receptor antagonists&#xD;
      before and after renal blood vessels clamp and release results in a significantly reduced&#xD;
      renal function injury.&#xD;
&#xD;
      On the basis of these results, we chose to divide the study population into 2 groups: control&#xD;
      group that would be treated the standard accepted preventive treatment: intravenous injection&#xD;
      of Mannitol, cooling of the kidney surface, compared to the treatment group that in addition&#xD;
      would receive pre- and post-operative treatment of endothelial receptor antagonists&#xD;
      (Ambrisentan (Volibris (10mg).&#xD;
&#xD;
      To be noticed that the drug is recognized and is given as a primary indication for patients&#xD;
      with pulmonary hypertension.&#xD;
&#xD;
      The differences between the renal function and biomarkers for pre- and post-operative renal&#xD;
      ischemic injury would be examined in order to disclose if the kidney injury of the treated&#xD;
      group was indeed smaller.&#xD;
&#xD;
      This information will enable us to protect the operated kidneys from the ischemic damage,&#xD;
      especially in those patients with poor basic renal function.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a study aimed at examining the protective effect of endothelin antagonism on the&#xD;
      ischemic damage the kidney undergoes during partial nephrectomy for kidney lesion removal.&#xD;
&#xD;
      In such procedure, it is common to clamp the kidney blood vessels in order to eliminate blood&#xD;
      flow in the surgical field that will enable clear visibility to differentiate the tumor&#xD;
      tissue from the normally kidney parenchyma.&#xD;
&#xD;
      Later, after removing the tumor lesion and suturing the tumor bed, the blockage is released&#xD;
      and the renal blood flow returns.&#xD;
&#xD;
      The blockage itself and its release causes damage to the kidney tissue that is usually&#xD;
      reduced by the kidney's cooling (through ice crystals)and as well as intravenous injection of&#xD;
      mannitol.&#xD;
&#xD;
      In this study, patients were divided into 2 groups randomly, assigned the receipt in the&#xD;
      order of recruitment.&#xD;
&#xD;
      The first group will receive the standard treatment and the other will be given before and&#xD;
      after surgery endothelin antagonists in addition to the standard treatment. The drug will be&#xD;
      given once a day for 5 days, starting 48 hours before surgery. Treatment efficacy assessment&#xD;
      will be based on comparison of renal function (serum creatinine level and glomerular&#xD;
      filtration) as well as biomarkers of acute renal damage (NGAL, KIM-1, and others) that will&#xD;
      be taken from patients before and at different time points after surgery: urine samples to be&#xD;
      taken at the following time points: - 3 , 8,24,48,72 hours after surgery. Blood samples will&#xD;
      be taken at the following time points: - 8, 24, 48, 72 hours after surgery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">October 11, 2018</start_date>
  <completion_date type="Anticipated">October 1, 2020</completion_date>
  <primary_completion_date type="Actual">February 1, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>RENAL FUNCTION INJURY</measure>
    <time_frame>2 YEARS</time_frame>
    <description>quantified by serum CRE, KIM-1,NGAL and urine markers KIM-1 NGAL</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Kidney Failure, Acute</condition>
  <arm_group>
    <arm_group_label>Treated group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Tab. Volibris 10mg given once a day for 5 days, starting 48 hours before surgery (in addition for the standard treatment for partial nephrectomy)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Treated with the standard treatment for partial nephrectomy</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ambrisentan 10 MG</intervention_name>
    <description>be given once a day for 5 days, starting 48 hours before surgery</description>
    <arm_group_label>Treated group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with a single kidney lesion who undergo Contrast enhancement (by CT scan)&#xD;
&#xD;
          2. Normal contra-lateral kidney as illustrated by imaging tests&#xD;
&#xD;
          3. Patients eligible for anesthesia and surgery&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with chronic kidney infections&#xD;
&#xD;
          2. Blood clot disorders&#xD;
&#xD;
          3. End-stage renal failure&#xD;
&#xD;
          4. Patients sensitive to the study drug&#xD;
&#xD;
          5. Patients with cardiac heart failure, EF &lt;40%&#xD;
&#xD;
          6. Patients with hyperkalemia&#xD;
&#xD;
          7. Patients with systolic blood pressure under 90 mmHg&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ofir Avitan, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Bnai-zion medical center, Haifa, Israel</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Bnai-Zion Medical Center</name>
      <address>
        <city>Haifa</city>
        <zip>3339419</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Physiology, The Bruce and Ruth Rapapport Faculty of Medicine, Technion</name>
      <address>
        <city>Haifa</city>
        <zip>3525408</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 24, 2020</study_first_submitted>
  <study_first_submitted_qc>June 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 29, 2020</study_first_posted>
  <last_update_submitted>June 24, 2020</last_update_submitted>
  <last_update_submitted_qc>June 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Bnai Zion Medical Center</investigator_affiliation>
    <investigator_full_name>Ofir. Avitan</investigator_full_name>
    <investigator_title>Dr. Avitan Ofir</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Renal Insufficiency</mesh_term>
    <mesh_term>Acute Kidney Injury</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ambrisentan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Only the Patients index and the collected data will be provided without private names or ID numbers</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/NCT04450095
org study id: 0048-18-BNZ
nct id: NCT04450095
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Based on animal studies, it was found that administration of endothelial receptor antagonists
      before and after renal blood vessels clamp and release results in a significantly reduced
      renal function injury.

      On the basis of these results, we chose to divide the study population into 2 groups: control
      group that would be treated the standard accepted preventive treatment: intravenous injection
      of Mannitol, cooling of the kidney surface, compared to the treatment group that in addition
      would receive pre- and post-operative treatment of endothelial receptor antagonists
      (Ambrisentan (Volibris (10mg).

      To be noticed that the drug is recognized and is given as a primary indication for patients
      with pulmonary hypertension.

      The differences between the renal function and biomarkers for pre- and post-operative renal
      ischemic injury would be examined in order to disclose if the kidney injury of the treated
      group was indeed smaller.

      This information will enable us to protect the operated kidneys from the ischemic damage,
      especially in those patients with poor basic renal function.
This is a study aimed at examining the protective effect of endothelin antagonism on the
      ischemic damage the kidney undergoes during partial nephrectomy for kidney lesion removal.

      In such procedure, it is common to clamp the kidney blood vessels in order to eliminate blood
      flow in the surgical field that will enable clear visibility to differentiate the tumor
      tissue from the normally kidney parenchyma.

      Later, after removing the tumor lesion and suturing the tumor bed, the blockage is released
      and the renal blood flow returns.

      The blockage itself and its release causes damage to the kidney tissue that is usually
      reduced by the kidney's cooling (through ice crystals)and as well as intravenous injection of
      mannitol.

      In this study, patients were divided into 2 groups randomly, assigned the receipt in the
      order of recruitment.

      The first group will receive the standard treatment and the other will be given before and
      after surgery endothelin antagonists in addition to the standard treatment. The drug will be
      given once a day for 5 days, starting 48 hours before surgery. Treatment efficacy assessment
      will be based on comparison of renal function (serum creatinine level and glomerular
      filtration) as well as biomarkers of acute renal damage (NGAL, KIM-1, and others) that will
      be taken from patients before and at different time points after surgery: urine samples to be
      taken at the following time points: - 3 , 8,24,48,72 hours after surgery. Blood samples will
      be taken at the following time points: - 8, 24, 48, 72 hours after surgery.
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: RENAL FUNCTION INJURY
time frame: 2 YEARS
description: quantified by serum CRE, KIM-1,NGAL and urine markers KIM-1 NGAL
arm group label: Treated group
arm group type: Active Comparator
description: Tab. Volibris 10mg given once a day for 5 days, starting 48 hours before surgery (in addition for the standard treatment for partial nephrectomy)
arm group label: Control group
arm group type: No Intervention
description: Treated with the standard treatment for partial nephrectomy
intervention type: Drug
intervention name: Ambrisentan 10 MG
description: be given once a day for 5 days, starting 48 hours before surgery
arm group label: Treated group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ofir Avitan, M.D.
role: Principal Investigator
affiliation: Bnai-zion medical center, Haifa, Israel
facility: 
facility: 
country: Israel
responsible party type: Principal Investigator
investigator affiliation: Bnai Zion Medical Center
investigator full name: Ofir. Avitan
investigator title: Dr. Avitan Ofir
mesh term: Renal Insufficiency
mesh term: Acute Kidney Injury
mesh term: Ambrisentan
sharing ipd: No
ipd description: Only the Patients index and the collected data will be provided without private names or ID numbers