<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/NCT03251690</url>
  </required_header>
  <id_info>
    <org_study_id>ID09-59-06</org_study_id>
    <nct_id>NCT03251690</nct_id>
  </id_info>
  <brief_title>Switching TDF/FTC/EFV to TDF/FTC/RPV VS Continuing TDF/FTC/EFV in HIV Patients With Complete Virological Suppression</brief_title>
  <acronym>STEREOS</acronym>
  <official_title>Switching Tenofovir/Emtricitabine/Efavirenz to Tenofovir/Emtricitabine/Rilpivirine Versus Continuing Tenofovir/Emtricitabine/Efavirenz in HIV1-infected Patients With Complete Virological Suppression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mahidol University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mahidol University</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      According to the Thai National Guidelines for Treatment of HIV/AIDS 2014, the recommended&#xD;
      first line ART regimen was 2 NRTIs backbone, TDF and FTC; plus 1 NNRTI, EFV, with RPV as an&#xD;
      alternative one. Most of the randomized-controlled studies, including ECHO and THRIVE, showed&#xD;
      the non-inferiority of RPV compared with EFV in naive cases. But there were not much&#xD;
      randomized-controlled trials for changing from other NRTI to RPV in patients who currently on&#xD;
      another ART, especially in Thailand. Moreover, the concerned adverse effects of dyslipidemia&#xD;
      and neurological symptoms were better in RPV-based than EFV-based regimen. Finally, the&#xD;
      cost-effectiveness and universal coverage are also the benefit of RPV over EFV in term of&#xD;
      economics.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      According to the Thai National Guidelines for Treatment of HIV/AIDS 2014, the recommended&#xD;
      first line ART (Anti-retroviral therapy) regimen was 2 NRTIs (nucleoside reverse&#xD;
      transcriptase inhibitors) backbone, which are TDF (Tenofovir) and FTC (Emtricitabine); plus 1&#xD;
      NNRTI (non-nucleoside reverse transcriptase inhibitor), which is EFV (Efavirenz), with RPV&#xD;
      (Rilpivirine) as an alternative in this class of drug.&#xD;
&#xD;
      Most of the randomized-controlled studies, including ECHO (Rilpivirine versus efavirenz with&#xD;
      tenofovir and emtricitabine in treatment-naive adults infected with HIV-1) and THRIVE&#xD;
      (Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse&#xD;
      transcriptase inhibitors in treatment-naive adults infected with HIV-1), the major trials&#xD;
      about RPV, showed the non-inferiority in efficacy of RPV compared with that of EFV in&#xD;
      treatment-naive cases with blood HIV viral load less than 500,000 copies/mL. But there were&#xD;
      not many trials focusing on changing the ART-regimens from other NRTI to RPV in patients who&#xD;
      currently on another ART, especially in randomized-controlled design. There were some studies&#xD;
      comparing continuing current regimens versus changing to Rilpivirine-based regimens, but they&#xD;
      didn't exclusively select the homogeneous drug components. In Thailand, study of changing to&#xD;
      Rilpivirine-based regimens was primarily designed to evaluate the adverse outcome about&#xD;
      dyslipidemia, whereas efficacy was a secondary outcome. Most studies, the concerned adverse&#xD;
      effects of dyslipidemia and neurological symptoms were better in RPV-based than EFV-based&#xD;
      regimen. Finally, the cost-effectiveness and universal coverage are also the benefit of RPV&#xD;
      over EFV in term of economics.&#xD;
&#xD;
      Therefore, we design this study to evaluate the efficacy; in term of non-inferiority, of the&#xD;
      newer, safer, and cheaper drug, Rilpivirine, to Efavirenz, the general-use drug with&#xD;
      acceptable efficacy, in the virological-suppressed patients currently on ART. Besides, we&#xD;
      also assess the adverse outcomes and factors associated with successful or failure of&#xD;
      treatment. In addition, we can have more backup data in term of national economics.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 27, 2016</start_date>
  <completion_date type="Actual">April 30, 2018</completion_date>
  <primary_completion_date type="Actual">April 30, 2018</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Sustained virological response</measure>
    <time_frame>12 months</time_frame>
    <description>maintain the undetectable HIV viral load</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Lipid adverse outcome</measure>
    <time_frame>12 months</time_frame>
    <description>Different in blood lipid profiles, including triglycerides, cholesterol, HDL, and LDL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neurological adverse outcome</measure>
    <time_frame>12 months</time_frame>
    <description>Neurological adverse events such as dizziness</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost -saving after switching regimens</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">246</enrollment>
  <condition>Anti-Retroviral Agents</condition>
  <condition>Efavirenz</condition>
  <condition>HIV-1-infection</condition>
  <condition>Sustained Virologic Response</condition>
  <condition>Dyslipidemias</condition>
  <condition>Rilpivirine</condition>
  <arm_group>
    <arm_group_label>Switching TDF/FTC/EFV to TDF/FTC/RPV</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Switching from Tenofovir 300 mg/day + Emtricitabine 200 mg/day + Efavirenz 600 mg/day (once daily) to Tenofovir 300 mg/day + Emtricitabine 200 mg/day + Rilpivirine 25 mg/day (once daily) Intervention: Tenofovir/Emtricitabine/Rilpivirine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Continuing TDF/FTC/EFV</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Continuing Tenofovir 300 mg/day + Emtricitabine 200 mg/day + Efavirenz 600 mg/day Intervention: Tenofovir/Emtricitabine/Efavirenz</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenofovir/Emtricitabine/Rilpivirine</intervention_name>
    <description>Tenofovir/Emtricitabine/Rilpivirine to compare the non-inferiority of efficacy and adverse effects to Tenofovir/Emtricitabine/Efavirenz in patients with virological suppression</description>
    <arm_group_label>Switching TDF/FTC/EFV to TDF/FTC/RPV</arm_group_label>
    <other_name>TDF/FTC/RPV</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenofovir/Emtricitabine/Efavirenz</intervention_name>
    <description>as a active comparator</description>
    <arm_group_label>Continuing TDF/FTC/EFV</arm_group_label>
    <other_name>TDF/FTC/EFV</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  on TDF/FTC/EFV for more than 3 months&#xD;
&#xD;
          -  Blood HIV RNA viral load &lt;50 copies/mL&#xD;
&#xD;
          -  CD4+ count &gt;200 cells/mm3&#xD;
&#xD;
          -  eligible to sign the informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  history of NRTI resistance&#xD;
&#xD;
          -  on medication that potentially interact with study drug&#xD;
&#xD;
          -  denied to participate in the study&#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>Sirichai Wiriyatanakorn, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Somneuk Sungkanuparp, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University</affiliation>
  </overall_official>
  <reference>
    <citation>Thai AIDS Society. Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2014. Nontaburi: Bureau of AIDS, TB, and STIs, 2014.</citation>
  </reference>
  <results_reference>
    <citation>Molina JM, Cahn P, Grinsztejn B, Lazzarin A, Mills A, Saag M, Supparatpinyo K, Walmsley S, Crauwels H, Rimsky LT, Vanveggel S, Boven K; ECHO study group. Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial. Lancet. 2011 Jul 16;378(9787):238-46. doi: 10.1016/S0140-6736(11)60936-7.</citation>
    <PMID>21763936</PMID>
  </results_reference>
  <results_reference>
    <citation>Cohen CJ, Andrade-Villanueva J, Clotet B, Fourie J, Johnson MA, Ruxrungtham K, Wu H, Zorrilla C, Crauwels H, Rimsky LT, Vanveggel S, Boven K; THRIVE study group. Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial. Lancet. 2011 Jul 16;378(9787):229-37. doi: 10.1016/S0140-6736(11)60983-5.</citation>
    <PMID>21763935</PMID>
  </results_reference>
  <results_reference>
    <citation>Thamrongwonglert P, Chetchotisakd P, Anunnatsiri S, Mootsikapun P. Improvement of lipid profiles when switching from efavirenz to rilpivirine in HIV-infected patients with dyslipidemia. HIV Clin Trials. 2016 Feb;17(1):12-6. doi: 10.1080/15284336.2015.1112480. Epub 2016 Jan 7.</citation>
    <PMID>26739573</PMID>
  </results_reference>
  <results_reference>
    <citation>Gianotti N, Poli A, Nozza S, Spagnuolo V, Tambussi G, Bossolasco S, Cinque P, Maillard M, Cernuschi M, Galli L, Lazzarin A, Castagna A. Efficacy and safety in clinical practice of a rilpivirine, tenofovir and emtricitabine single-tablet regimen in virologically suppressed HIV-positive patients on stable antiretroviral therapy. J Int AIDS Soc. 2015 Jul 30;18(1):20037. doi: 10.7448/IAS.18.1.20037. eCollection 2015.</citation>
    <PMID>26232000</PMID>
  </results_reference>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>August 14, 2017</study_first_submitted>
  <study_first_submitted_qc>August 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 16, 2017</study_first_posted>
  <last_update_submitted>May 4, 2019</last_update_submitted>
  <last_update_submitted_qc>May 4, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dyslipidemias</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</mesh_term>
    <mesh_term>Emtricitabine</mesh_term>
    <mesh_term>Efavirenz</mesh_term>
    <mesh_term>Rilpivirine</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/NCT03251690
org study id: ID09-59-06
nct id: NCT03251690
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
According to the Thai National Guidelines for Treatment of HIV/AIDS 2014, the recommended
      first line ART regimen was 2 NRTIs backbone, TDF and FTC; plus 1 NNRTI, EFV, with RPV as an
      alternative one. Most of the randomized-controlled studies, including ECHO and THRIVE, showed
      the non-inferiority of RPV compared with EFV in naive cases. But there were not much
      randomized-controlled trials for changing from other NRTI to RPV in patients who currently on
      another ART, especially in Thailand. Moreover, the concerned adverse effects of dyslipidemia
      and neurological symptoms were better in RPV-based than EFV-based regimen. Finally, the
      cost-effectiveness and universal coverage are also the benefit of RPV over EFV in term of
      economics.
According to the Thai National Guidelines for Treatment of HIV/AIDS 2014, the recommended
      first line ART (Anti-retroviral therapy) regimen was 2 NRTIs (nucleoside reverse
      transcriptase inhibitors) backbone, which are TDF (Tenofovir) and FTC (Emtricitabine); plus 1
      NNRTI (non-nucleoside reverse transcriptase inhibitor), which is EFV (Efavirenz), with RPV
      (Rilpivirine) as an alternative in this class of drug.

      Most of the randomized-controlled studies, including ECHO (Rilpivirine versus efavirenz with
      tenofovir and emtricitabine in treatment-naive adults infected with HIV-1) and THRIVE
      (Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse
      transcriptase inhibitors in treatment-naive adults infected with HIV-1), the major trials
      about RPV, showed the non-inferiority in efficacy of RPV compared with that of EFV in
      treatment-naive cases with blood HIV viral load less than 500,000 copies/mL. But there were
      not many trials focusing on changing the ART-regimens from other NRTI to RPV in patients who
      currently on another ART, especially in randomized-controlled design. There were some studies
      comparing continuing current regimens versus changing to Rilpivirine-based regimens, but they
      didn't exclusively select the homogeneous drug components. In Thailand, study of changing to
      Rilpivirine-based regimens was primarily designed to evaluate the adverse outcome about
      dyslipidemia, whereas efficacy was a secondary outcome. Most studies, the concerned adverse
      effects of dyslipidemia and neurological symptoms were better in RPV-based than EFV-based
      regimen. Finally, the cost-effectiveness and universal coverage are also the benefit of RPV
      over EFV in term of economics.

      Therefore, we design this study to evaluate the efficacy; in term of non-inferiority, of the
      newer, safer, and cheaper drug, Rilpivirine, to Efavirenz, the general-use drug with
      acceptable efficacy, in the virological-suppressed patients currently on ART. Besides, we
      also assess the adverse outcomes and factors associated with successful or failure of
      treatment. In addition, we can have more backup data in term of national economics.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Sustained virological response
time frame: 12 months
description: maintain the undetectable HIV viral load
measure: Lipid adverse outcome
time frame: 12 months
description: Different in blood lipid profiles, including triglycerides, cholesterol, HDL, and LDL
measure: Neurological adverse outcome
time frame: 12 months
description: Neurological adverse events such as dizziness
measure: Cost -saving after switching regimens
time frame: 12 months
arm group label: Switching TDF/FTC/EFV to TDF/FTC/RPV
arm group type: Experimental
description: Switching from Tenofovir 300 mg/day + Emtricitabine 200 mg/day + Efavirenz 600 mg/day (once daily) to Tenofovir 300 mg/day + Emtricitabine 200 mg/day + Rilpivirine 25 mg/day (once daily) Intervention: Tenofovir/Emtricitabine/Rilpivirine
arm group label: Continuing TDF/FTC/EFV
arm group type: Active Comparator
description: Continuing Tenofovir 300 mg/day + Emtricitabine 200 mg/day + Efavirenz 600 mg/day Intervention: Tenofovir/Emtricitabine/Efavirenz
intervention type: Drug
intervention name: Tenofovir/Emtricitabine/Rilpivirine
description: Tenofovir/Emtricitabine/Rilpivirine to compare the non-inferiority of efficacy and adverse effects to Tenofovir/Emtricitabine/Efavirenz in patients with virological suppression
arm group label: Switching TDF/FTC/EFV to TDF/FTC/RPV
other name: TDF/FTC/RPV
intervention type: Drug
intervention name: Tenofovir/Emtricitabine/Efavirenz
description: as a active comparator
arm group label: Continuing TDF/FTC/EFV
other name: TDF/FTC/EFV
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sirichai Wiriyatanakorn, MD
role: Principal Investigator
affiliation: Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University
last name: Somneuk Sungkanuparp, MD
role: Principal Investigator
affiliation: Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University
citation: Thai AIDS Society. Thailand National Guidelines on HIV/AIDS Treatment and Prevention 2014. Nontaburi: Bureau of AIDS, TB, and STIs, 2014.
citation: Molina JM, Cahn P, Grinsztejn B, Lazzarin A, Mills A, Saag M, Supparatpinyo K, Walmsley S, Crauwels H, Rimsky LT, Vanveggel S, Boven K; ECHO study group. Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial. Lancet. 2011 Jul 16;378(9787):238-46. doi: 10.1016/S0140-6736(11)60936-7.
PMID: 21763936
citation: Cohen CJ, Andrade-Villanueva J, Clotet B, Fourie J, Johnson MA, Ruxrungtham K, Wu H, Zorrilla C, Crauwels H, Rimsky LT, Vanveggel S, Boven K; THRIVE study group. Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial. Lancet. 2011 Jul 16;378(9787):229-37. doi: 10.1016/S0140-6736(11)60983-5.
PMID: 21763935
citation: Thamrongwonglert P, Chetchotisakd P, Anunnatsiri S, Mootsikapun P. Improvement of lipid profiles when switching from efavirenz to rilpivirine in HIV-infected patients with dyslipidemia. HIV Clin Trials. 2016 Feb;17(1):12-6. doi: 10.1080/15284336.2015.1112480. Epub 2016 Jan 7.
PMID: 26739573
citation: Gianotti N, Poli A, Nozza S, Spagnuolo V, Tambussi G, Bossolasco S, Cinque P, Maillard M, Cernuschi M, Galli L, Lazzarin A, Castagna A. Efficacy and safety in clinical practice of a rilpivirine, tenofovir and emtricitabine single-tablet regimen in virologically suppressed HIV-positive patients on stable antiretroviral therapy. J Int AIDS Soc. 2015 Jul 30;18(1):20037. doi: 10.7448/IAS.18.1.20037. eCollection 2015.
PMID: 26232000
responsible party type: Sponsor
mesh term: Dyslipidemias
mesh term: Tenofovir
mesh term: Emtricitabine
mesh term: Efavirenz
mesh term: Rilpivirine