<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/NCT04487990</url>
  </required_header>
  <id_info>
    <org_study_id>U1111-1252-0194</org_study_id>
    <secondary_id>33351120.0.0000.0068</secondary_id>
    <nct_id>NCT04487990</nct_id>
  </id_info>
  <brief_title>CoV-Hep Study: Regional Anticoagulation Modalities in Continuous Venous Venous Hemodialysis in Patients With COVID-19</brief_title>
  <official_title>CoV-Hep Study: Randomized and Paired Clinical Trial Comparing Regional Anticoagulation Modalities in Continuous Venous Venous Hemodialysis in Patients With COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sao Paulo General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Sao Paulo General Hospital</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Since the emergence of the new strain of betacoronavirus (SARS-CoV-2) and its important&#xD;
      clinical repercussions, it has been described that patients with its associated pneumonia&#xD;
      (COVID-19) have high rates of thrombotic events, including reduction in the dialyzers patency&#xD;
      when undergoing renal replacement therapy. Several strategies for preventing the early loss&#xD;
      of dialysers are described, and regional anticoagulation based on citrate is the preferred&#xD;
      modality for preventing this complication. On the other hand, in patients with SARS-CoV-2&#xD;
      there are already descriptions of endothelial inflammation and activation of the coagulation&#xD;
      cascade, including studies demonstrating the benefit of heparinization of these patients.&#xD;
      Thus, this study aims to compare two different anticoagulation strategies in patients&#xD;
      infected with COVID-19 with continued venovenous hemodialysis (CVVHD). From the indication of&#xD;
      CVVHD, patients will be screened according to eligibility criteria and, if they fit these&#xD;
      parameters, they will be randomized into two groups: Group A - Standard regional&#xD;
      anticoagulation based on Citrate associated with infusion of low doses of unfractionated&#xD;
      heparin 10ui/kg/hour and Group B - Standard regional anticoagulation based on Citrate only.&#xD;
      Patients will be randomized in blocks and followed for 72 hours. The primary endpoint is&#xD;
      dialyzer patency at the end of 72 hours of clinical follow-up. Secondary objectives will be&#xD;
      mortality, bleeding rate, drop in hematimetric indices, urea sieving, filter time in hours,&#xD;
      down time of therapy, system and dialyser pressures (PBE and PTM). All patients will undergo&#xD;
      a standard procedure with a prescribed dose of 30mL/Kg/H, blood flow of 150mL/minute and&#xD;
      polysulfone dialyzer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After randomization, patients will be allocated to one of two groups:&#xD;
&#xD;
      Control group (n = 45): patients on continuous hemodialysis (blood flow 150 ml / min, dose of&#xD;
      30 ml / kg / h) receiving anticoagulation with sodium citrate at 4 mmol / l. The dialysis&#xD;
      system pressures, dialyzer patency and duration and bleeding rate will be assessed for 72&#xD;
      hours;&#xD;
&#xD;
      Intervention group (n = 45): patients on continuous hemodialysis (blood flow 150 ml / min,&#xD;
      dose of 30 ml / kg / h) receiving anticoagulation with sodium citrate at 4 mmol / l&#xD;
      associated with unfractionated heparin at 10U / Kg / h. The dialysis system pressures,&#xD;
      dialyzer patency and duration and bleeding rate will be assessed for 72 hours.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 29, 2020</start_date>
  <completion_date type="Actual">April 3, 2021</completion_date>
  <primary_completion_date type="Actual">March 31, 2021</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>
    <intervention_model_description>Clinical trial of treatment, randomized-controlled, parallel, open, with two arms</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clotted dialyzers</measure>
    <time_frame>Day 3 of dialysis</time_frame>
    <description>The percentage of clotted dialyzers within 72 hours in each of the studied groups.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time-free of clotting</measure>
    <time_frame>Day 3 of dialysis</time_frame>
    <description>Number of hours until a dialyzer clots in the first 72 hours of dialysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of dialyzers used</measure>
    <time_frame>Day 3 of dialysis</time_frame>
    <description>The amount of dialyzers used in the first 72 hours of hemodialysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pressure variation</measure>
    <time_frame>Day 3 of dialysis</time_frame>
    <description>Variation in dialysis system and vascular access pressures in the first 72 h of dialysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urea sieving</measure>
    <time_frame>Day 3 of dialysis</time_frame>
    <description>Variation in urea sieving between the first, second and third days of dialysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Downtime of dialysis</measure>
    <time_frame>Day 3 of dialysis</time_frame>
    <description>Time of dialysis stop due to clotting in the first 72 hours</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">118</enrollment>
  <condition>Acute Kidney Injury</condition>
  <condition>Covid19</condition>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients on continuous hemodialysis (blood flow 150 ml / min, dose of 30 ml / kg / h) receiving anticoagulation with sodium citrate at 4 mmol / l.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intervention group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients on continuous hemodialysis (blood flow 150 ml / min, dose of 30 ml / kg / h) receiving anticoagulation with sodium citrate at 4 mmol / l associated with unfractionated heparin at 10U / Kg / h.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>unfractionated Heparin</intervention_name>
    <description>Addition of unfractioned heparin to CVVHD system already running under citrate regional anticoagulation.</description>
    <arm_group_label>Intervention group</arm_group_label>
    <other_name>No associated drug</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed or probable SARS-CoV-2 infection;&#xD;
&#xD;
          -  Presence of acute kidney injury with indication and agreement between ICU and&#xD;
             nephrology teams for the introduction of renal continuous venous venous hemodialysis.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hypersensitivity to any of the substances used in the study (Citric acid dextrosol&#xD;
             2.2% and unfractionated heparin);&#xD;
&#xD;
          -  Previous diagnosis of coagulopathy or thrombophilia;&#xD;
&#xD;
          -  Contraindication to the use of unfractionated heparin by the assistant team;&#xD;
&#xD;
          -  Risk of citrate poisoning - (Lactate&gt; 30mg / dL, RNI&gt; 2.5, Total bilirubin&gt; 15mg /&#xD;
             dL);&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paulo Lins, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of São Paulo General Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Camila Rodrigues, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of São Paulo General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of São Paulo General Hospital</name>
      <address>
        <city>São Paulo</city>
        <state>SP</state>
        <zip>05403-010</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>July 23, 2020</study_first_submitted>
  <study_first_submitted_qc>July 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2020</study_first_posted>
  <last_update_submitted>June 7, 2022</last_update_submitted>
  <last_update_submitted_qc>June 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>acute kidney injury</keyword>
  <keyword>continuous venovenous hemodialysis</keyword>
  <keyword>anticoagulation</keyword>
  <keyword>heparin</keyword>
  <keyword>citrate</keyword>
  <keyword>covid-19</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</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>Heparin</mesh_term>
    <mesh_term>Calcium heparin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT04487990
org study id: U1111-1252-0194
secondary id: 33351120.0.0000.0068
nct id: NCT04487990
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Since the emergence of the new strain of betacoronavirus (SARS-CoV-2) and its important
      clinical repercussions, it has been described that patients with its associated pneumonia
      (COVID-19) have high rates of thrombotic events, including reduction in the dialyzers patency
      when undergoing renal replacement therapy. Several strategies for preventing the early loss
      of dialysers are described, and regional anticoagulation based on citrate is the preferred
      modality for preventing this complication. On the other hand, in patients with SARS-CoV-2
      there are already descriptions of endothelial inflammation and activation of the coagulation
      cascade, including studies demonstrating the benefit of heparinization of these patients.
      Thus, this study aims to compare two different anticoagulation strategies in patients
      infected with COVID-19 with continued venovenous hemodialysis (CVVHD). From the indication of
      CVVHD, patients will be screened according to eligibility criteria and, if they fit these
      parameters, they will be randomized into two groups: Group A - Standard regional
      anticoagulation based on Citrate associated with infusion of low doses of unfractionated
      heparin 10ui/kg/hour and Group B - Standard regional anticoagulation based on Citrate only.
      Patients will be randomized in blocks and followed for 72 hours. The primary endpoint is
      dialyzer patency at the end of 72 hours of clinical follow-up. Secondary objectives will be
      mortality, bleeding rate, drop in hematimetric indices, urea sieving, filter time in hours,
      down time of therapy, system and dialyser pressures (PBE and PTM). All patients will undergo
      a standard procedure with a prescribed dose of 30mL/Kg/H, blood flow of 150mL/minute and
      polysulfone dialyzer.
After randomization, patients will be allocated to one of two groups:

      Control group (n = 45): patients on continuous hemodialysis (blood flow 150 ml / min, dose of
      30 ml / kg / h) receiving anticoagulation with sodium citrate at 4 mmol / l. The dialysis
      system pressures, dialyzer patency and duration and bleeding rate will be assessed for 72
      hours;

      Intervention group (n = 45): patients on continuous hemodialysis (blood flow 150 ml / min,
      dose of 30 ml / kg / h) receiving anticoagulation with sodium citrate at 4 mmol / l
      associated with unfractionated heparin at 10U / Kg / h. The dialysis system pressures,
      dialyzer patency and duration and bleeding rate will be assessed for 72 hours.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Clinical trial of treatment, randomized-controlled, parallel, open, with two arms
primary purpose: Treatment
masking: None (Open Label)
measure: Clotted dialyzers
time frame: Day 3 of dialysis
description: The percentage of clotted dialyzers within 72 hours in each of the studied groups.
measure: Time-free of clotting
time frame: Day 3 of dialysis
description: Number of hours until a dialyzer clots in the first 72 hours of dialysis
measure: Number of dialyzers used
time frame: Day 3 of dialysis
description: The amount of dialyzers used in the first 72 hours of hemodialysis
measure: Pressure variation
time frame: Day 3 of dialysis
description: Variation in dialysis system and vascular access pressures in the first 72 h of dialysis
measure: Urea sieving
time frame: Day 3 of dialysis
description: Variation in urea sieving between the first, second and third days of dialysis
measure: Downtime of dialysis
time frame: Day 3 of dialysis
description: Time of dialysis stop due to clotting in the first 72 hours
arm group label: Control group
arm group type: No Intervention
description: Patients on continuous hemodialysis (blood flow 150 ml / min, dose of 30 ml / kg / h) receiving anticoagulation with sodium citrate at 4 mmol / l.
arm group label: Intervention group
arm group type: Experimental
description: Patients on continuous hemodialysis (blood flow 150 ml / min, dose of 30 ml / kg / h) receiving anticoagulation with sodium citrate at 4 mmol / l associated with unfractionated heparin at 10U / Kg / h.
intervention type: Drug
intervention name: unfractionated Heparin
description: Addition of unfractioned heparin to CVVHD system already running under citrate regional anticoagulation.
arm group label: Intervention group
other name: No associated drug
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Paulo Lins, MD
role: Principal Investigator
affiliation: University of São Paulo General Hospital
last name: Camila Rodrigues, MD, PhD
role: Principal Investigator
affiliation: University of São Paulo General Hospital
facility: 
country: Brazil
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Acute Kidney Injury
mesh term: Heparin
mesh term: Calcium heparin
sharing ipd: No