<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/NCT04463784</url>
  </required_header>
  <id_info>
    <org_study_id>CACT 1809</org_study_id>
    <nct_id>NCT04463784</nct_id>
  </id_info>
  <brief_title>Efficacy of Efavirenz 400mg vs. 600mg Combined With Lamivudine and Tenofovir in Treatment Naive HIV Infection</brief_title>
  <official_title>Peking Union Medical College Hospital</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking Union Medical College Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peking Union Medical College 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The present study will be a randomized controlled study in which 500 treatment-naive HIV&#xD;
      patients will be randomized 1:1 to Efaviren 400mg v.s. 600mg combined with lamivudine and&#xD;
      tenofovir. The whole cohort will be followed for two years. Efficacy and safety of each&#xD;
      regimen will be evaluated throughout the study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      As efaviren has been commonly used as the first-line therapy in HIV infection worldwide, its&#xD;
      major side effect i.e. the mental effects have been noticed and has a major influence on the&#xD;
      adherence and efficacy of ART regimen. Mental effects of efaviren have been especially&#xD;
      critical in Chinese patients, as the effective and toxic ranges of efaviren plasma&#xD;
      concentration in Chinese patients are very close to each other.&#xD;
&#xD;
      In this study, 500 treatment-naive Chinese patients with a body weight &lt; 60kg will be&#xD;
      screened and recruited. Patients will be randomized 1:1 to efaviren 400mg v.s. 600mg combined&#xD;
      with lamivudine and tenofovir. All patients will be followed regularly for 2 years, at 0, 2w,&#xD;
      4w, 3m and every 3 months. Virological and immunological measurements will be done at each&#xD;
      visit. Meanwhile, various mental scales will be performed at each visit to evaluate the&#xD;
      mental effects of each arm.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">April 1, 2018</start_date>
  <completion_date type="Anticipated">August 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2020</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>Change from Baseline Virological measurements at 12 weeks</measure>
    <time_frame>12 weeks</time_frame>
    <description>Plasma viral load</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline Virological measurements at 24 weeks</measure>
    <time_frame>24 weeks</time_frame>
    <description>Plasma viral load</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline Virological measurements at 48 weeks</measure>
    <time_frame>48 weeks</time_frame>
    <description>Plasma viral load</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline Virological measurements at 72 weeks</measure>
    <time_frame>72 weeks</time_frame>
    <description>Plasma viral load</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline Virological measurements at 96 weeks</measure>
    <time_frame>96 weeks</time_frame>
    <description>Plasma viral load</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline Immunological measurements at 12 weeks</measure>
    <time_frame>12 weeks</time_frame>
    <description>CD4 T cell count</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline Immunological measurements at 24 weeks</measure>
    <time_frame>24 weeks</time_frame>
    <description>CD4 T cell count</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline Immunological measurements at 48 weeks</measure>
    <time_frame>48 weeks</time_frame>
    <description>CD4 T cell count</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline Immunological measurements at 72 weeks</measure>
    <time_frame>72 weeks</time_frame>
    <description>CD4 T cell count</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline Immunological measurements at 96 weeks</measure>
    <time_frame>96 weeks</time_frame>
    <description>CD4 T cell count</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse effects measured by Dizziness Handicap Inventory</measure>
    <time_frame>0, 12, 24, 48, 72, 96 weeks</time_frame>
    <description>Measure statistically significant difference in perception of dizziness by administering the Dizziness Handicap Inventory (DHI) between two groups at different time point. The 25-item tool comprises three sub-scales: physical (DHI-P; 7 items), emotional (DHI-E; 9 items), and functional (DHI-F; 9 items) and each item is scored from 0 to 4. Grading standard: 0-30 points is defiend as minor obstacles, 31-60 points as moderate obstacle, and 61-100 points as serious obstacle with high risk of falling.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse effects measured by Hamilton Depression Scale-24</measure>
    <time_frame>0, 12, 24, 48, 72, 96 weeks</time_frame>
    <description>Measure statistically significant difference in perception of depression by administering the Hamilton Depression Scale-24 (HAMD-24) between two groups at different time point. The Hamilton Depression Rating Scale (HAMD) has a total of 24 items. 14 items were scored from 0 to 4, and 10 items were scored from 0 to 2. The total score that less than 8 points is defined as no depression, 8 to 20 points as may be depression, scores that more than 20 is defined as mild or moderate depression, and more than 35 points as severe depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse effects measured by Pittsburgh Sleep Quality Index</measure>
    <time_frame>0, 12, 24, 48, 72, 96 weeks</time_frame>
    <description>Measure statistically significant difference in perception of sleep quality by administering the Pittsburgh Sleep Quality Index (PSQI) between two groups at different time point. PSQI was used to assess the sleep quality of subjects in the last month. It consists of 19 self-evaluation items and 5 other evaluation items, of which only 18 self-evaluation items participate in scoring. 18 items constitute 7 components, and each component is scored according to 0 ~ 3 grades. The PSQI total score ranges from 0 to 21. The higher the score indicates the worser sleep quality.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">500</enrollment>
  <condition>HIV/AIDS</condition>
  <condition>Mental Impairment</condition>
  <arm_group>
    <arm_group_label>Efavirenz 400MG Oral Tablet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Recruited treatment-naive HIV infected patients will be given Lamivudin 300mg per day, tenofovir 300mg per day and efavirenz 400mg per day as antiretroviral treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Efavirenz 600MG Oral Tablet</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Recruited treatment-naive HIV infected patients will be given Lamivudin 300mg per day, tenofovir 300mg per day and efavirenz 600mg per day, per standard dose.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Efavirenz 400Mg Oral Tablet</intervention_name>
    <description>The experimental arm will receive 400mg efavirenz per randomization with other two antiretroviral medication (tenofovir and lamivudine).</description>
    <arm_group_label>Efavirenz 400MG Oral Tablet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Efavirenz 600Mg Oral Tablet</intervention_name>
    <description>The active comparator arm will receive 600mg efavirenz per randomization with other two antiretroviral medication (tenofovir and lamivudine).</description>
    <arm_group_label>Efavirenz 600MG Oral Tablet</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provision of signed and dated informed consent form&#xD;
&#xD;
          -  Willingness and availability to engage in study activities for the duration of the&#xD;
             study&#xD;
&#xD;
          -  Age between 18-65&#xD;
&#xD;
          -  Documented HIV-1 infection (confirmed by Western blot)&#xD;
&#xD;
          -  Received no prior antiretroviral therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy or breastfeeding or anticipated pregnancy in two years&#xD;
&#xD;
          -  History of AIDS-defining illness&#xD;
&#xD;
          -  Hemoglobin &lt; 9g/dl；or peripheral white blood cell counts &lt; 2000/μl；or neutrophil&#xD;
             counts &lt; 1000 /μl；or platelet count &lt; 75,000/μl；&#xD;
&#xD;
          -  Liver disease (transaminase and alkaline phosphatase levels more than three times the&#xD;
             upper limit of the normal range (ULN), bilirubin level more than 2.5 times the ULN)&#xD;
&#xD;
          -  Chronic kidney disease (serum creatinine level more than 1.5 times the ULN)&#xD;
&#xD;
          -  Patients with a history of injection drug usage&#xD;
&#xD;
          -  Patients with a history of mental disorders&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Taisheng Li, PhD, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking Union Medical College Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Peking Union Medical College Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 15, 2018</study_first_submitted>
  <study_first_submitted_qc>July 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 9, 2020</study_first_posted>
  <last_update_submitted>July 3, 2020</last_update_submitted>
  <last_update_submitted_qc>July 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Peking Union Medical College Hospital</investigator_affiliation>
    <investigator_full_name>LI Taisheng</investigator_full_name>
    <investigator_title>Chief, Department of Infectious Diseases</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acquired Immunodeficiency Syndrome</mesh_term>
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Efavirenz</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/NCT04463784
org study id: CACT 1809
nct id: NCT04463784
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The present study will be a randomized controlled study in which 500 treatment-naive HIV
      patients will be randomized 1:1 to Efaviren 400mg v.s. 600mg combined with lamivudine and
      tenofovir. The whole cohort will be followed for two years. Efficacy and safety of each
      regimen will be evaluated throughout the study.
As efaviren has been commonly used as the first-line therapy in HIV infection worldwide, its
      major side effect i.e. the mental effects have been noticed and has a major influence on the
      adherence and efficacy of ART regimen. Mental effects of efaviren have been especially
      critical in Chinese patients, as the effective and toxic ranges of efaviren plasma
      concentration in Chinese patients are very close to each other.

      In this study, 500 treatment-naive Chinese patients with a body weight < 60kg will be
      screened and recruited. Patients will be randomized 1:1 to efaviren 400mg v.s. 600mg combined
      with lamivudine and tenofovir. All patients will be followed regularly for 2 years, at 0, 2w,
      4w, 3m and every 3 months. Virological and immunological measurements will be done at each
      visit. Meanwhile, various mental scales will be performed at each visit to evaluate the
      mental effects of each arm.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change from Baseline Virological measurements at 12 weeks
time frame: 12 weeks
description: Plasma viral load
measure: Change from Baseline Virological measurements at 24 weeks
time frame: 24 weeks
description: Plasma viral load
measure: Change from Baseline Virological measurements at 48 weeks
time frame: 48 weeks
description: Plasma viral load
measure: Change from Baseline Virological measurements at 72 weeks
time frame: 72 weeks
description: Plasma viral load
measure: Change from Baseline Virological measurements at 96 weeks
time frame: 96 weeks
description: Plasma viral load
measure: Change from Baseline Immunological measurements at 12 weeks
time frame: 12 weeks
description: CD4 T cell count
measure: Change from Baseline Immunological measurements at 24 weeks
time frame: 24 weeks
description: CD4 T cell count
measure: Change from Baseline Immunological measurements at 48 weeks
time frame: 48 weeks
description: CD4 T cell count
measure: Change from Baseline Immunological measurements at 72 weeks
time frame: 72 weeks
description: CD4 T cell count
measure: Change from Baseline Immunological measurements at 96 weeks
time frame: 96 weeks
description: CD4 T cell count
measure: Adverse effects measured by Dizziness Handicap Inventory
time frame: 0, 12, 24, 48, 72, 96 weeks
description: Measure statistically significant difference in perception of dizziness by administering the Dizziness Handicap Inventory (DHI) between two groups at different time point. The 25-item tool comprises three sub-scales: physical (DHI-P; 7 items), emotional (DHI-E; 9 items), and functional (DHI-F; 9 items) and each item is scored from 0 to 4. Grading standard: 0-30 points is defiend as minor obstacles, 31-60 points as moderate obstacle, and 61-100 points as serious obstacle with high risk of falling.
measure: Adverse effects measured by Hamilton Depression Scale-24
time frame: 0, 12, 24, 48, 72, 96 weeks
description: Measure statistically significant difference in perception of depression by administering the Hamilton Depression Scale-24 (HAMD-24) between two groups at different time point. The Hamilton Depression Rating Scale (HAMD) has a total of 24 items. 14 items were scored from 0 to 4, and 10 items were scored from 0 to 2. The total score that less than 8 points is defined as no depression, 8 to 20 points as may be depression, scores that more than 20 is defined as mild or moderate depression, and more than 35 points as severe depression.
measure: Adverse effects measured by Pittsburgh Sleep Quality Index
time frame: 0, 12, 24, 48, 72, 96 weeks
description: Measure statistically significant difference in perception of sleep quality by administering the Pittsburgh Sleep Quality Index (PSQI) between two groups at different time point. PSQI was used to assess the sleep quality of subjects in the last month. It consists of 19 self-evaluation items and 5 other evaluation items, of which only 18 self-evaluation items participate in scoring. 18 items constitute 7 components, and each component is scored according to 0 ~ 3 grades. The PSQI total score ranges from 0 to 21. The higher the score indicates the worser sleep quality.
arm group label: Efavirenz 400MG Oral Tablet
arm group type: Experimental
description: Recruited treatment-naive HIV infected patients will be given Lamivudin 300mg per day, tenofovir 300mg per day and efavirenz 400mg per day as antiretroviral treatment.
arm group label: Efavirenz 600MG Oral Tablet
arm group type: Active Comparator
description: Recruited treatment-naive HIV infected patients will be given Lamivudin 300mg per day, tenofovir 300mg per day and efavirenz 600mg per day, per standard dose.
intervention type: Drug
intervention name: Efavirenz 400Mg Oral Tablet
description: The experimental arm will receive 400mg efavirenz per randomization with other two antiretroviral medication (tenofovir and lamivudine).
arm group label: Efavirenz 400MG Oral Tablet
intervention type: Drug
intervention name: Efavirenz 600Mg Oral Tablet
description: The active comparator arm will receive 600mg efavirenz per randomization with other two antiretroviral medication (tenofovir and lamivudine).
arm group label: Efavirenz 600MG Oral Tablet
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Taisheng Li, PhD, MD
role: Principal Investigator
affiliation: Peking Union Medical College Hospital
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Peking Union Medical College Hospital
investigator full name: LI Taisheng
investigator title: Chief, Department of Infectious Diseases
mesh term: Acquired Immunodeficiency Syndrome
mesh term: HIV Infections
mesh term: Efavirenz