<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/NCT03776851</url>
  </required_header>
  <id_info>
    <org_study_id>347-HGNPE-2018</org_study_id>
    <nct_id>NCT03776851</nct_id>
  </id_info>
  <brief_title>Erythropoietin in Hemolytic Uremic Syndrome</brief_title>
  <official_title>Effect of Erythropoietin on Red Blood Cell Requirement in Children With Hemolytic Uremic Syndrome: a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital General de Niños Pedro de Elizalde</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital General de Niños Pedro de Elizalde</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>
      This study will evaluate the impact of early administration of erythropoietin in the number&#xD;
      of red blood cell transfusions in children with Shiga toxin-producing Escherichia coli&#xD;
      hemolytic uremic syndrome (STEC-HUS).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Introduction:&#xD;
&#xD;
      Anemia in STEC-HUS is treated with red blood cell (RBC) transfusions. It can causes&#xD;
      hypervolemia, hyperkalemia, exacerbate the thrombotic state of the disease, transmit&#xD;
      infectious agents and trigger antigenic sensitization. Anemia is mainly due to hemolysis, but&#xD;
      deficit of erythropoietin synthesis (EPO) may aggravate it. Although recombinant human EPO is&#xD;
      frequently used in children with STEC-HUS there is no adequate evidence of its benefit. If it&#xD;
      is confirmed that EPO reduce the number of RBC transfusions, its administration could&#xD;
      diminish the aforementioned risks and also reduce costs.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To determine if EPO administration decreases the number of RBC transfusions and; secondarily,&#xD;
      to assess if its levels influence on transfusion requirement.&#xD;
&#xD;
      Methodology:&#xD;
&#xD;
      Randomized, open controlled clinical trial. We will include 28 patients (14 per arm) &lt;18&#xD;
      years with STEC-HUS admitted to our hospital. They will be grouped after randomization:(1)&#xD;
      One to standard of care (RBC transfusions with hemoglobin ≤7 mg / dl and/or hemodynamic&#xD;
      instability) and (2) the other to standard of care plus EPO (50 u / kg subcutaneous three&#xD;
      times weekly) and RBC transfusions with hemoglobin ≤7 mg / dl). Serum EPO will be measured by&#xD;
      ELISA and together with the clinical and laboratory variables, association with RBC&#xD;
      transfusions number will be sought. Written informed consent and assent when appropriate,&#xD;
      will be requested prior to enter into the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2019</start_date>
  <completion_date type="Actual">December 30, 2020</completion_date>
  <primary_completion_date type="Actual">December 30, 2020</primary_completion_date>
  <phase>Phase 4</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>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of RBC transfusions</measure>
    <time_frame>At the end of the 36 month study recruiting period</time_frame>
    <description>To determine if administration of erythropoietin decreases the number of RBC during the acute stage of hemolytic uremic syndrome</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Erythropoietin levels</measure>
    <time_frame>At the end of the 36 month study recruiting period</time_frame>
    <description>To determine if erythropoietin levels correlate with RBC transfusions requirement.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Hemolytic-Uremic Syndrome</condition>
  <condition>Anemia</condition>
  <arm_group>
    <arm_group_label>Erythropoietin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Erythropoietin plus standard of care (RBC transfusions if Hb ≤7 mg/dl and/or hemodynamic instability)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No Intervention</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Standard of care: RBC transfusions if Hb ≤7 mg/dl and/or hemodynamic instability</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>erythropoietin</intervention_name>
    <description>erythropoietin 50 International Units (IU) per kilogram three times weekly by subcutaneous route</description>
    <arm_group_label>Erythropoietin</arm_group_label>
    <other_name>EPO</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Post diarrheal HUS: Prodrome of enteritis followed by microangiopathic hemolytic&#xD;
             anemia, thrombocytopenia and signs of renal damage (increased plasma creatinine,&#xD;
             proteinuria, and / or hematuria). Proven STEC infection wiil not be required to enter&#xD;
             into the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Atypical HUS&#xD;
&#xD;
          -  HUS associated with systemic diseases (pneumococcal infection, HIV, Systemic lupus&#xD;
             erythematosus) or drugs&#xD;
&#xD;
          -  Anemia or known kidney disease&#xD;
&#xD;
          -  Previously transfused or treated with erythropoietin&#xD;
&#xD;
          -  Contraindications to erythropoietin&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Month</minimum_age>
    <maximum_age>18 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alejandro Balestracci, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital General de Niños Pedro de Elizalde</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>HGNPE</name>
      <address>
        <city>Caba</city>
        <zip>1417</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
  </location_countries>
  <reference>
    <citation>Ardissino G, Dacco V, Testa S, Civitillo CF, Tel F, Possenti I, Belingheri M, Castorina P, Bolsa-Ghiringhelli N, Tedeschi S, Paglialonga F, Salardi S, Consonni D, Zoia E, Salice P, Chidini G. Hemoconcentration: a major risk factor for neurological involvement in hemolytic uremic syndrome. Pediatr Nephrol. 2015 Feb;30(2):345-52. doi: 10.1007/s00467-014-2918-0. Epub 2014 Aug 23.</citation>
    <PMID>25149851</PMID>
  </reference>
  <reference>
    <citation>Scheiring J, Rosales A, Zimmerhackl LB. Clinical practice. Today's understanding of the haemolytic uraemic syndrome. Eur J Pediatr. 2010 Jan;169(1):7-13. doi: 10.1007/s00431-009-1039-4. Epub 2009 Aug 26.</citation>
    <PMID>19707787</PMID>
  </reference>
  <reference>
    <citation>Exeni R, Donato H, Rendo P, Antonuccio M, Rapetti MC, Grimoldi I, Exeni A, de Galvagni A, Trepacka E, Amore A. Low levels of serum erythropoietin in children with endemic hemolytic uremic syndrome. Pediatr Nephrol. 1998 Apr;12(3):226-30. doi: 10.1007/s004670050443.</citation>
    <PMID>9630043</PMID>
  </reference>
  <reference>
    <citation>Moore E, Bellomo R. Erythropoietin (EPO) in acute kidney injury. Ann Intensive Care. 2011 Mar 21;1(1):3. doi: 10.1186/2110-5820-1-3.</citation>
    <PMID>21906325</PMID>
  </reference>
  <reference>
    <citation>Warady BA, Silverstein DM. Management of anemia with erythropoietic-stimulating agents in children with chronic kidney disease. Pediatr Nephrol. 2014 Sep;29(9):1493-505. doi: 10.1007/s00467-013-2557-x. Epub 2013 Sep 5.</citation>
    <PMID>24005791</PMID>
  </reference>
  <reference>
    <citation>Pape L, Ahlenstiel T, Kreuzer M, Drube J, Froede K, Franke D, Ehrich JH, Haubitz M. Early erythropoietin reduced the need for red blood cell transfusion in childhood hemolytic uremic syndrome: a randomized prospective pilot trial. Pediatr Nephrol. 2009 May;24(5):1061-4. doi: 10.1007/s00467-008-1087-4. Epub 2008 Dec 16.</citation>
    <PMID>19085014</PMID>
  </reference>
  <reference>
    <citation>Balestracci A, Martin SM, Toledo I, Alvarado C, Wainsztein RE. Early erythropoietin in post-diarrheal hemolytic uremic syndrome: a case-control study. Pediatr Nephrol. 2015 Feb;30(2):339-44. doi: 10.1007/s00467-014-2911-7. Epub 2014 Aug 21.</citation>
    <PMID>25138373</PMID>
  </reference>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>December 11, 2018</study_first_submitted>
  <study_first_submitted_qc>December 13, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 17, 2018</study_first_posted>
  <last_update_submitted>January 11, 2021</last_update_submitted>
  <last_update_submitted_qc>January 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital General de Niños Pedro de Elizalde</investigator_affiliation>
    <investigator_full_name>Alejandro Balestracci</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Hemolytic-Uremic Syndrome</keyword>
  <keyword>erythropoietin</keyword>
  <keyword>RBC transfusion</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Azotemia</mesh_term>
    <mesh_term>Hemolytic-Uremic Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Hemolysis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epoetin Alfa</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The authors will share the generated data with qualified external researchers during the next 5 years after article publication. All data provided will be anonymized to respect the privacy of patients who have participated in the trail in line with applicable laws and regulations.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>During the next 5 years after article publication.</ipd_time_frame>
    <ipd_access_criteria>Qualified external researchers</ipd_access_criteria>
  </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/NCT03776851
org study id: 347-HGNPE-2018
nct id: NCT03776851
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study will evaluate the impact of early administration of erythropoietin in the number
      of red blood cell transfusions in children with Shiga toxin-producing Escherichia coli
      hemolytic uremic syndrome (STEC-HUS).
Introduction:

      Anemia in STEC-HUS is treated with red blood cell (RBC) transfusions. It can causes
      hypervolemia, hyperkalemia, exacerbate the thrombotic state of the disease, transmit
      infectious agents and trigger antigenic sensitization. Anemia is mainly due to hemolysis, but
      deficit of erythropoietin synthesis (EPO) may aggravate it. Although recombinant human EPO is
      frequently used in children with STEC-HUS there is no adequate evidence of its benefit. If it
      is confirmed that EPO reduce the number of RBC transfusions, its administration could
      diminish the aforementioned risks and also reduce costs.

      Objective:

      To determine if EPO administration decreases the number of RBC transfusions and; secondarily,
      to assess if its levels influence on transfusion requirement.

      Methodology:

      Randomized, open controlled clinical trial. We will include 28 patients (14 per arm) <18
      years with STEC-HUS admitted to our hospital. They will be grouped after randomization:(1)
      One to standard of care (RBC transfusions with hemoglobin ≤7 mg / dl and/or hemodynamic
      instability) and (2) the other to standard of care plus EPO (50 u / kg subcutaneous three
      times weekly) and RBC transfusions with hemoglobin ≤7 mg / dl). Serum EPO will be measured by
      ELISA and together with the clinical and laboratory variables, association with RBC
      transfusions number will be sought. Written informed consent and assent when appropriate,
      will be requested prior to enter into the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Number of RBC transfusions
time frame: At the end of the 36 month study recruiting period
description: To determine if administration of erythropoietin decreases the number of RBC during the acute stage of hemolytic uremic syndrome
measure: Erythropoietin levels
time frame: At the end of the 36 month study recruiting period
description: To determine if erythropoietin levels correlate with RBC transfusions requirement.
arm group label: Erythropoietin
arm group type: Experimental
description: Erythropoietin plus standard of care (RBC transfusions if Hb ≤7 mg/dl and/or hemodynamic instability)
arm group label: No Intervention
arm group type: No Intervention
description: Standard of care: RBC transfusions if Hb ≤7 mg/dl and/or hemodynamic instability
intervention type: Drug
intervention name: erythropoietin
description: erythropoietin 50 International Units (IU) per kilogram three times weekly by subcutaneous route
arm group label: Erythropoietin
other name: EPO
criteria: 
gender: All
minimum age: 1 Month
maximum age: 18 Years
healthy volunteers: No
last name: Alejandro Balestracci, MD, PhD
role: Principal Investigator
affiliation: Hospital General de Niños Pedro de Elizalde
facility: 
country: Argentina
citation: Ardissino G, Dacco V, Testa S, Civitillo CF, Tel F, Possenti I, Belingheri M, Castorina P, Bolsa-Ghiringhelli N, Tedeschi S, Paglialonga F, Salardi S, Consonni D, Zoia E, Salice P, Chidini G. Hemoconcentration: a major risk factor for neurological involvement in hemolytic uremic syndrome. Pediatr Nephrol. 2015 Feb;30(2):345-52. doi: 10.1007/s00467-014-2918-0. Epub 2014 Aug 23.
PMID: 25149851
citation: Scheiring J, Rosales A, Zimmerhackl LB. Clinical practice. Today's understanding of the haemolytic uraemic syndrome. Eur J Pediatr. 2010 Jan;169(1):7-13. doi: 10.1007/s00431-009-1039-4. Epub 2009 Aug 26.
PMID: 19707787
citation: Exeni R, Donato H, Rendo P, Antonuccio M, Rapetti MC, Grimoldi I, Exeni A, de Galvagni A, Trepacka E, Amore A. Low levels of serum erythropoietin in children with endemic hemolytic uremic syndrome. Pediatr Nephrol. 1998 Apr;12(3):226-30. doi: 10.1007/s004670050443.
PMID: 9630043
citation: Moore E, Bellomo R. Erythropoietin (EPO) in acute kidney injury. Ann Intensive Care. 2011 Mar 21;1(1):3. doi: 10.1186/2110-5820-1-3.
PMID: 21906325
citation: Warady BA, Silverstein DM. Management of anemia with erythropoietic-stimulating agents in children with chronic kidney disease. Pediatr Nephrol. 2014 Sep;29(9):1493-505. doi: 10.1007/s00467-013-2557-x. Epub 2013 Sep 5.
PMID: 24005791
citation: Pape L, Ahlenstiel T, Kreuzer M, Drube J, Froede K, Franke D, Ehrich JH, Haubitz M. Early erythropoietin reduced the need for red blood cell transfusion in childhood hemolytic uremic syndrome: a randomized prospective pilot trial. Pediatr Nephrol. 2009 May;24(5):1061-4. doi: 10.1007/s00467-008-1087-4. Epub 2008 Dec 16.
PMID: 19085014
citation: Balestracci A, Martin SM, Toledo I, Alvarado C, Wainsztein RE. Early erythropoietin in post-diarrheal hemolytic uremic syndrome: a case-control study. Pediatr Nephrol. 2015 Feb;30(2):339-44. doi: 10.1007/s00467-014-2911-7. Epub 2014 Aug 21.
PMID: 25138373
responsible party type: Principal Investigator
investigator affiliation: Hospital General de Niños Pedro de Elizalde
investigator full name: Alejandro Balestracci
investigator title: Principal Investigator
mesh term: Azotemia
mesh term: Hemolytic-Uremic Syndrome
mesh term: Syndrome
mesh term: Hemolysis
mesh term: Epoetin Alfa
sharing ipd: Yes
ipd description: The authors will share the generated data with qualified external researchers during the next 5 years after article publication. All data provided will be anonymized to respect the privacy of patients who have participated in the trail in line with applicable laws and regulations.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: During the next 5 years after article publication.
ipd access criteria: Qualified external researchers