<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/NCT02209740</url>
  </required_header>
  <id_info>
    <org_study_id>TDFOUT</org_study_id>
    <secondary_id>218/12 revised</secondary_id>
    <nct_id>NCT02209740</nct_id>
  </id_info>
  <brief_title>Renal and Bone Outcome After Switching Tenofovir to Different Antiretroviral Strategies</brief_title>
  <acronym>TDFOUT</acronym>
  <official_title>A Prospective, Cohort Study of Renal and Bone Outcome After Changing Tenofovir in Patients With Renal Toxicity According to Antiretroviral Strategy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Asociacion para el Estudio de las Enfermedades Infecciosas</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Asociacion para el Estudio de las Enfermedades Infecciosas</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Renal outcome could be different after switching tenofovir to different antiretroviral&#xD;
      strategies, in case of renal toxicity. Therefore, it is necessary to evaluate the importance&#xD;
      of renal evolution in these patients, in terms of grade and time to renal improvement,&#xD;
      according to the different options after interrupting tenofovir. The aim of this study was to&#xD;
      explore the renal outcome after tenofovir according to new antiretroviral regimen.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Renal toxicity has become an important issue in a large number of HIV infected patients&#xD;
      receiving a tenofovir-containing regimen. However, there are no data about the best&#xD;
      antiretroviral regimen in patients switching tenofovir because of renal toxicity, in time,&#xD;
      grade or persistence of renal improvement. Thus, patients with renal toxicity on tenofovir,&#xD;
      defined as:&#xD;
&#xD;
        -  a progressive decrease of at least 25% of estimated glomerular filtration rate (GFR, by&#xD;
           chronic kidney disease-epi equation), or&#xD;
&#xD;
        -  confirmed value of GFR below 60 ml/min in two successive determinations, or&#xD;
&#xD;
        -  proximal tubular renal dysfunction, as indicated by the presence of at least 3 of the&#xD;
           following parameters: proteinuria&gt; 150 mg/g; excretion fractional of phosphorus in urine&#xD;
           &gt; 20%; glucosuria &gt; 150 mg; or/and tubular proteinuria/albuminuria ratio above 0.4.&#xD;
&#xD;
      who changed to the combination of abacavir plus a third drug, or to a nucleoside&#xD;
      analogues-free antiretroviral combination (dual therapy, monotherapy) will be followed for 1&#xD;
      year to establish the time and grade of improvement (defined as the lack of above criteria).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Renal outcome</measure>
    <time_frame>48 weeks</time_frame>
    <description>Evolution of renal parameters after switching tenofovir according to antiretroviral drug or regimen used, in terms of GFR (glomerular filtration rate by Chronic Kidney Disease-epidemiological collaboration equation) improvement, increase in excretion fractional of phosphorus in urine, decrease in proteinuria, and in glycosuria. As control group, renal outcome will be evaluated in patients continuing TDF-based therapy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Antiviral efficacy</measure>
    <time_frame>48 weeks</time_frame>
    <description>Number of patients without virological failure, defined as an HIV RNA level above 37 copies/ml, 48 weeks after the change of tenofovir</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bone mineral density (BMD) changes</measure>
    <time_frame>48 weeks</time_frame>
    <description>Changes in BMD in the subgroup of patients with two successive BMD measurements, before and after TDF switch, according to baseline risk factors for BMD change (age, body mass index, hypovitaminosis D, secondary hyperparathyroidism), in comparison with patients continuing TDF</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Antiviral safety</measure>
    <time_frame>48 weeks</time_frame>
    <description>Number (and percentage) and degree of adverse events, and percentage of therapy withdrawal, according to antiretroviral strategy after the change of tenofovir</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">245</enrollment>
  <condition>Renal Disease</condition>
  <arm_group>
    <arm_group_label>Tenofovir switch</arm_group_label>
    <description>Patients switched tenofovir to different antiretroviral regimen according to physicians decision</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Tenofovir switch</intervention_name>
    <description>Patients switched tenofovir to different antiretroviral regimen according to physicians decision</description>
    <arm_group_label>Tenofovir switch</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        HIV-infected patients in regular clinical and analytical follow up, receiving a&#xD;
        tenofovir-containing regimen&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  HIV-infected patients&#xD;
&#xD;
          -  Older than 18 years&#xD;
&#xD;
          -  Receiving a Tenofovir-containing regimen, and with criteria of renal toxicity (see&#xD;
             above)&#xD;
&#xD;
          -  Switching the antiretroviral regimen&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Patients receiving prolonged therapy with other nephrotoxic drugs&#xD;
&#xD;
          -  Patients not receiving or interrupting antiretroviral regimen&#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>Jose L Casado, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Asociacion para el Estudio de las Enfermedades Infecciosas</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Ramon y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>December 2015</verification_date>
  <study_first_submitted>August 2, 2014</study_first_submitted>
  <study_first_submitted_qc>August 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 6, 2014</study_first_posted>
  <last_update_submitted>December 28, 2015</last_update_submitted>
  <last_update_submitted_qc>December 28, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 30, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Asociacion para el Estudio de las Enfermedades Infecciosas</investigator_affiliation>
    <investigator_full_name>Jose L. Casado</investigator_full_name>
    <investigator_title>Clinical Investigator</investigator_title>
  </responsible_party>
  <keyword>renal toxicity, HIV, antiretroviral, outcome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</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/NCT02209740
org study id: TDFOUT
secondary id: 218/12 revised
nct id: NCT02209740
lead sponsor: 
has dmc: No
Renal outcome could be different after switching tenofovir to different antiretroviral
      strategies, in case of renal toxicity. Therefore, it is necessary to evaluate the importance
      of renal evolution in these patients, in terms of grade and time to renal improvement,
      according to the different options after interrupting tenofovir. The aim of this study was to
      explore the renal outcome after tenofovir according to new antiretroviral regimen.
Renal toxicity has become an important issue in a large number of HIV infected patients
      receiving a tenofovir-containing regimen. However, there are no data about the best
      antiretroviral regimen in patients switching tenofovir because of renal toxicity, in time,
      grade or persistence of renal improvement. Thus, patients with renal toxicity on tenofovir,
      defined as:

        -  a progressive decrease of at least 25% of estimated glomerular filtration rate (GFR, by
           chronic kidney disease-epi equation), or

        -  confirmed value of GFR below 60 ml/min in two successive determinations, or

        -  proximal tubular renal dysfunction, as indicated by the presence of at least 3 of the
           following parameters: proteinuria> 150 mg/g; excretion fractional of phosphorus in urine
           > 20%; glucosuria > 150 mg; or/and tubular proteinuria/albuminuria ratio above 0.4.

      who changed to the combination of abacavir plus a third drug, or to a nucleoside
      analogues-free antiretroviral combination (dual therapy, monotherapy) will be followed for 1
      year to establish the time and grade of improvement (defined as the lack of above criteria).
observational model: Cohort
time perspective: Prospective
measure: Renal outcome
time frame: 48 weeks
description: Evolution of renal parameters after switching tenofovir according to antiretroviral drug or regimen used, in terms of GFR (glomerular filtration rate by Chronic Kidney Disease-epidemiological collaboration equation) improvement, increase in excretion fractional of phosphorus in urine, decrease in proteinuria, and in glycosuria. As control group, renal outcome will be evaluated in patients continuing TDF-based therapy
measure: Antiviral efficacy
time frame: 48 weeks
description: Number of patients without virological failure, defined as an HIV RNA level above 37 copies/ml, 48 weeks after the change of tenofovir
measure: Bone mineral density (BMD) changes
time frame: 48 weeks
description: Changes in BMD in the subgroup of patients with two successive BMD measurements, before and after TDF switch, according to baseline risk factors for BMD change (age, body mass index, hypovitaminosis D, secondary hyperparathyroidism), in comparison with patients continuing TDF
measure: Antiviral safety
time frame: 48 weeks
description: Number (and percentage) and degree of adverse events, and percentage of therapy withdrawal, according to antiretroviral strategy after the change of tenofovir
arm group label: Tenofovir switch
description: Patients switched tenofovir to different antiretroviral regimen according to physicians decision
intervention type: Other
intervention name: Tenofovir switch
description: Patients switched tenofovir to different antiretroviral regimen according to physicians decision
arm group label: Tenofovir switch
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jose L Casado, MD
role: Principal Investigator
affiliation: Asociacion para el Estudio de las Enfermedades Infecciosas
facility: 
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Asociacion para el Estudio de las Enfermedades Infecciosas
investigator full name: Jose L. Casado
investigator title: Clinical Investigator
mesh term: Kidney Diseases
mesh term: Tenofovir