<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/NCT01666301</url>
  </required_header>
  <id_info>
    <org_study_id>Epo-Loc1</org_study_id>
    <nct_id>NCT01666301</nct_id>
  </id_info>
  <brief_title>ESAs, Reticulocyte Dynamic and Hemoglobin Variability</brief_title>
  <official_title>Reticulocyte Dynamic and Related Hemoglobin Variability in Hemodialysis Patients Treated With Darbepoetin Alfa and C.E.R.A.: a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ospedale Regionale di Locarno</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ospedale Regionale di Locarno</source>
  <brief_summary>
    <textblock>
      Background: In a simulation based on a pharmacokinetic model we demonstrated that increasing&#xD;
      the erythropoiesis stimulating agents (ESAs) half-life or shortening their administration&#xD;
      interval decreases hemoglobin variability. The benefit of reducing the administration&#xD;
      interval was however lessened by the variability induced by more frequent dosage adjustments.&#xD;
      The purpose of this study was to analyze the reticulocyte and hemoglobin kinetics under&#xD;
      different ESAs and administration intervals in a collective of chronic hemodialysis patients.&#xD;
&#xD;
      Methods: The study was designed as an open-label, randomized, four-period cross-over&#xD;
      investigation, including 30 patients under chronic hemodialysis at the regional hospital of&#xD;
      Locarno (Switzerland) in September 2009 and lasting 2 years. Four treatment strategies&#xD;
      (C.E.R.A. every 4 weeks Q4W and every 2 weeks Q2W, Darbepoetin alfa Q4W and Q2W) were&#xD;
      compared with each other. The mean square successive difference of hemoglobin, reticulocyte&#xD;
      count and ESAs dose was used to quantify variability. We distinguished a short- and a&#xD;
      long-term variability based respectively on the weekly and monthly successive difference.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>February 2010</start_date>
  <completion_date type="Actual">April 2012</completion_date>
  <primary_completion_date type="Actual">April 2012</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>hemoglobin variability</measure>
    <time_frame>2 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>differences in reticulocyte count over time</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>risk of hemoglobin overshooting (HR)</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>superiority of every 2 week administration</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>reticulocyte variability</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Erythropoiesis Stimulating Agent Pharmacodynamics</condition>
  <arm_group>
    <arm_group_label>C.E.R.A.</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>C.E.R.A. every 4 and then every 2 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Darbepoetin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Darbepoetin alfa every 4 and then every 2 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>comparison between darbepoetin alfa and C.E.R.A. and different administration intervals</intervention_name>
    <arm_group_label>C.E.R.A.</arm_group_label>
    <arm_group_label>Darbepoetin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  chronic patients aged 18 years or older, undergoing dialysis 3 times a week for at&#xD;
             least 8 weeks before screening, necessitating continuous subcutaneous treatment with&#xD;
             weekly Darbepoetin alfa or Erythropoietin beta to maintain hemoglobin (Hb) targets&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnancy; not respecting the inclusion criteria&#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>Luca Gabutti, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ospedale Regionale Locarno</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ospedale Regionale Locarno</name>
      <address>
        <city>Locarno</city>
        <state>Ticino</state>
        <zip>6600</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>August 2012</verification_date>
  <study_first_submitted>August 14, 2012</study_first_submitted>
  <study_first_submitted_qc>August 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 16, 2012</study_first_posted>
  <last_update_submitted>August 16, 2012</last_update_submitted>
  <last_update_submitted_qc>August 16, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 17, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ospedale Regionale di Locarno</investigator_affiliation>
    <investigator_full_name>Luca Gabutti, MD</investigator_full_name>
    <investigator_title>Head of Department; internal medicine</investigator_title>
  </responsible_party>
  <keyword>Erythropoietin stimulating agents</keyword>
  <keyword>Hemoglobin</keyword>
  <keyword>Reticulocytes</keyword>
  <keyword>Variability</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Darbepoetin alfa</mesh_term>
  </intervention_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/NCT01666301
org study id: Epo-Loc1
nct id: NCT01666301
lead sponsor: 
Background: In a simulation based on a pharmacokinetic model we demonstrated that increasing
      the erythropoiesis stimulating agents (ESAs) half-life or shortening their administration
      interval decreases hemoglobin variability. The benefit of reducing the administration
      interval was however lessened by the variability induced by more frequent dosage adjustments.
      The purpose of this study was to analyze the reticulocyte and hemoglobin kinetics under
      different ESAs and administration intervals in a collective of chronic hemodialysis patients.

      Methods: The study was designed as an open-label, randomized, four-period cross-over
      investigation, including 30 patients under chronic hemodialysis at the regional hospital of
      Locarno (Switzerland) in September 2009 and lasting 2 years. Four treatment strategies
      (C.E.R.A. every 4 weeks Q4W and every 2 weeks Q2W, Darbepoetin alfa Q4W and Q2W) were
      compared with each other. The mean square successive difference of hemoglobin, reticulocyte
      count and ESAs dose was used to quantify variability. We distinguished a short- and a
      long-term variability based respectively on the weekly and monthly successive difference.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: hemoglobin variability
time frame: 2 years
measure: differences in reticulocyte count over time
time frame: 2 years
measure: risk of hemoglobin overshooting (HR)
time frame: 2 years
measure: superiority of every 2 week administration
time frame: 2 years
measure: reticulocyte variability
time frame: 2 years
arm group label: C.E.R.A.
arm group type: Active Comparator
description: C.E.R.A. every 4 and then every 2 weeks
arm group label: Darbepoetin
arm group type: Active Comparator
description: Darbepoetin alfa every 4 and then every 2 weeks
intervention type: Drug
intervention name: comparison between darbepoetin alfa and C.E.R.A. and different administration intervals
arm group label: C.E.R.A.
arm group label: Darbepoetin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Luca Gabutti, MD
role: Principal Investigator
affiliation: Ospedale Regionale Locarno
facility: 
country: Switzerland
responsible party type: Principal Investigator
investigator affiliation: Ospedale Regionale di Locarno
investigator full name: Luca Gabutti, MD
investigator title: Head of Department; internal medicine
mesh term: Darbepoetin alfa