<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/NCT03825523</url>
  </required_header>
  <id_info>
    <org_study_id>C09-18</org_study_id>
    <nct_id>NCT03825523</nct_id>
  </id_info>
  <brief_title>Immediate ART in Subjects With Opportunistic Diseases</brief_title>
  <official_title>Impact of the Timing of Antiretroviral Therapy Initiation (Immediate Versus Early) on the Mortality Rate of HIV/AIDS Patients Hospitalized With an Opportunistic Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gustavo Reyes-Teran</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centro de Investigación en. Enfermedades Infecciosas, Mexico</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 aim of this study is to compare the clinical response and mortality rate by an&#xD;
      opportunistic disease in HIV-infected individuals who start immediate versus conventional&#xD;
      antiretroviral therapy.&#xD;
&#xD;
      Immediate ART (iART) is defined as starting antiretroviral therapy in the first 48 hours&#xD;
      after the hospitalization.&#xD;
&#xD;
      Conventional ART (cART) is defined as starting antiretroviral therapy once the opportunistic&#xD;
      infection is under control at the discretion of infectious disease specialist.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sample size was calculated using formula, of difference in proportions formula using a beta&#xD;
      of 0.1, alpha of 0.05 and an expected difference in mortality of 20%, The sample size is 225&#xD;
      subjects in each group. Informed consent will be obtained. Patients will be allocated to each&#xD;
      group (iART or cART) after randomization stratified by the CD4+ T cell count (less or more&#xD;
      than 50 cells/mm3).&#xD;
&#xD;
      Plasma viral load and CD4+ T cell count will be measured at study entry and at weeks 2, 4,&#xD;
      12, 24 and 48 after ART initiation. Clinical outcomes will be: mortality at 4, 12, 24, and 48&#xD;
      weeks, length of hospitalization (measured in days), clinical and microbiological cure of the&#xD;
      opportunistic disease, incidence and severity of immune reconstitution of inflammatory&#xD;
      syndrome (IRIS), and adverse drug reactions and interactions.&#xD;
&#xD;
      Once 50% of the sample size has completed 30 days of follow-up, a preliminary analysis will&#xD;
      be conducted to assess safety and efficacy of iART; if differences in the mortality are&#xD;
      observed, the study will be terminated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 18, 2019</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2023</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>
    <intervention_model_description>Stratified randomization will be generated by an electronic system, in blocks of 6 and 8, and a 1:1 ratio, according to the CD4+ T cell count.&#xD;
Group A: Immediate treatment (iART). Start ART within 48 hours of admission and hospitalization; Group B: Conventional treatment (cART). Start the ART once the opportunistic infection is under control at the discretion of infectious disease specialist.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mortality</measure>
    <time_frame>30 days</time_frame>
    <description>Compare mortality rates betweeno two groups according to the timing of ART initiation: immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assess survival rates</measure>
    <time_frame>90 days since starting antiretroviral therapy (ART)</time_frame>
    <description>Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess survival rates</measure>
    <time_frame>180 days since starting antiretroviral therapy (ART)</time_frame>
    <description>Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess survival rates</measure>
    <time_frame>360 days since starting antiretroviral therapy (ART)</time_frame>
    <description>Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of stay</measure>
    <time_frame>1 year</time_frame>
    <description>Compare length of hospitalization between both groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Asses survival rates by the CD4 count</measure>
    <time_frame>90 days</time_frame>
    <description>Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART) stratified by CD4+ T cell count at study entry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Asses survival rates by the CD4 count</measure>
    <time_frame>180 days</time_frame>
    <description>Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART) stratified by CD4+ T cell count at study entry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Asses survival rates by the CD4 count</measure>
    <time_frame>360 days</time_frame>
    <description>Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART) stratified by CD4+ T cell count at study entry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Viral load</measure>
    <time_frame>90 days</time_frame>
    <description>Measure the baseline plasma viral load and evaluate its dynamics after ART initiation in both groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Viral load</measure>
    <time_frame>180 days</time_frame>
    <description>Measure the baseline plasma viral load and evaluate its dynamics after ART initiation in both groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Viral load</measure>
    <time_frame>360 days</time_frame>
    <description>Measure the baseline plasma viral load and evaluate its dynamics after ART initiation in both groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CD4 T cell counts</measure>
    <time_frame>90 days</time_frame>
    <description>Measure CD4+ T cell counts, and evaluate its dynamics after ART initiation in both groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CD4 T cell counts</measure>
    <time_frame>180 days</time_frame>
    <description>Measure CD4+ T cell counts, and evaluate its dynamics after ART initiation in both groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CD4 T cell counts</measure>
    <time_frame>360 days</time_frame>
    <description>Measure CD4+ T cell counts, and evaluate its dynamics after ART initiation in both groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>IRIS</measure>
    <time_frame>48 weeks</time_frame>
    <description>Determine the incidence and severity of IRIS. Severity will be classified as mild or life threatening</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse reactions</measure>
    <time_frame>48 weeks</time_frame>
    <description>Describe ART-related adverse events, and drug interactions</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">448</enrollment>
  <condition>HIV/AIDS</condition>
  <condition>ANTIRETROVIRAL TREATMENT</condition>
  <arm_group>
    <arm_group_label>Group A Immediate treatment (iART)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Other: time to start the ART within 48 hours of admission to hospitalization</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B Conventional treatment (cART)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Other: time to start the ART, after the opportunistic disease has been controlled, at the discretion of infectious disease specialist.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>iART</intervention_name>
    <description>After group assignment, ART will be started within the first 48 hours after admission to the hospital. ART regimen will be decided according to each subject´s the clinical characteristics</description>
    <arm_group_label>Group A Immediate treatment (iART)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>cART</intervention_name>
    <description>After group assignment, ART is started at the discretion of the attending physician. ART regimen will be decided according to each subject´s the clinical characteristics</description>
    <arm_group_label>Group B Conventional treatment (cART)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Over 18 years old&#xD;
&#xD;
          -  Time from admission to study entry: less than 48 hours&#xD;
&#xD;
          -  Confirmed HIV diagnosis or high probability of HIV infection based on a positive HIV&#xD;
             rapid test&#xD;
&#xD;
          -  Having an opportunistic disease&#xD;
&#xD;
          -  Subjects must be naïve to ART or have failed their first or second ART regimen or must&#xD;
             have abandoned ART for more than 3 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Meningitis due to Cryptococcus spp. or for M. tuberculosis&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GUSTAVO MD REYES-TERÁN, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Instituto Nacional de Enfermedades Respiratorias</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>GUSTAVO MD REYES-TERÁN, M.D.</last_name>
    <phone>56667985</phone>
    <phone_ext>100</phone_ext>
    <email>gustavo.reyesteran@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Amy MD Peralta, M.D.</last_name>
    <phone>56667985</phone>
    <phone_ext>100</phone_ext>
    <email>amy.peralta@cieni.org.mx</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Centro de Investigacion en Enfermedades Infecciosas</name>
      <address>
        <city>Mexico</city>
        <zip>14080</zip>
        <country>Mexico</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gustavo Reyes-Teran, M.D.</last_name>
      <phone>+52(55)56667985</phone>
    </contact>
    <contact_backup>
      <last_name>Yuria Ablanedo-Terrazas, M.D.</last_name>
      <phone>+52(55)56667985</phone>
    </contact_backup>
    <investigator>
      <last_name>Gustavo Reyes-Teran, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Amy Bethel Peralta Prado, M.D.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>January 18, 2019</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 31, 2019</study_first_posted>
  <last_update_submitted>February 15, 2022</last_update_submitted>
  <last_update_submitted_qc>February 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 16, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Centro de Investigación en. Enfermedades Infecciosas, Mexico</investigator_affiliation>
    <investigator_full_name>Gustavo Reyes-Teran</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>HIV/AIDS</keyword>
  <keyword>ART</keyword>
  <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>
  <!-- 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/NCT03825523
org study id: C09-18
nct id: NCT03825523
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The aim of this study is to compare the clinical response and mortality rate by an
      opportunistic disease in HIV-infected individuals who start immediate versus conventional
      antiretroviral therapy.

      Immediate ART (iART) is defined as starting antiretroviral therapy in the first 48 hours
      after the hospitalization.

      Conventional ART (cART) is defined as starting antiretroviral therapy once the opportunistic
      infection is under control at the discretion of infectious disease specialist.
Sample size was calculated using formula, of difference in proportions formula using a beta
      of 0.1, alpha of 0.05 and an expected difference in mortality of 20%, The sample size is 225
      subjects in each group. Informed consent will be obtained. Patients will be allocated to each
      group (iART or cART) after randomization stratified by the CD4+ T cell count (less or more
      than 50 cells/mm3).

      Plasma viral load and CD4+ T cell count will be measured at study entry and at weeks 2, 4,
      12, 24 and 48 after ART initiation. Clinical outcomes will be: mortality at 4, 12, 24, and 48
      weeks, length of hospitalization (measured in days), clinical and microbiological cure of the
      opportunistic disease, incidence and severity of immune reconstitution of inflammatory
      syndrome (IRIS), and adverse drug reactions and interactions.

      Once 50% of the sample size has completed 30 days of follow-up, a preliminary analysis will
      be conducted to assess safety and efficacy of iART; if differences in the mortality are
      observed, the study will be terminated.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Stratified randomization will be generated by an electronic system, in blocks of 6 and 8, and a 1:1 ratio, according to the CD4+ T cell count.
Group A: Immediate treatment (iART). Start ART within 48 hours of admission and hospitalization; Group B: Conventional treatment (cART). Start the ART once the opportunistic infection is under control at the discretion of infectious disease specialist.
primary purpose: Treatment
masking: None (Open Label)
measure: Mortality
time frame: 30 days
description: Compare mortality rates betweeno two groups according to the timing of ART initiation: immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART)
measure: Assess survival rates
time frame: 90 days since starting antiretroviral therapy (ART)
description: Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART)
measure: Assess survival rates
time frame: 180 days since starting antiretroviral therapy (ART)
description: Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART)
measure: Assess survival rates
time frame: 360 days since starting antiretroviral therapy (ART)
description: Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART)
measure: Length of stay
time frame: 1 year
description: Compare length of hospitalization between both groups
measure: Asses survival rates by the CD4 count
time frame: 90 days
description: Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART) stratified by CD4+ T cell count at study entry
measure: Asses survival rates by the CD4 count
time frame: 180 days
description: Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART) stratified by CD4+ T cell count at study entry
measure: Asses survival rates by the CD4 count
time frame: 360 days
description: Compare the survival rate of HIV-infected patients on immediate antiretroviral therapy (iART) versus conventional antiretroviral therapy (cART) stratified by CD4+ T cell count at study entry
measure: Viral load
time frame: 90 days
description: Measure the baseline plasma viral load and evaluate its dynamics after ART initiation in both groups
measure: Viral load
time frame: 180 days
description: Measure the baseline plasma viral load and evaluate its dynamics after ART initiation in both groups
measure: Viral load
time frame: 360 days
description: Measure the baseline plasma viral load and evaluate its dynamics after ART initiation in both groups
measure: CD4 T cell counts
time frame: 90 days
description: Measure CD4+ T cell counts, and evaluate its dynamics after ART initiation in both groups
measure: CD4 T cell counts
time frame: 180 days
description: Measure CD4+ T cell counts, and evaluate its dynamics after ART initiation in both groups
measure: CD4 T cell counts
time frame: 360 days
description: Measure CD4+ T cell counts, and evaluate its dynamics after ART initiation in both groups
measure: IRIS
time frame: 48 weeks
description: Determine the incidence and severity of IRIS. Severity will be classified as mild or life threatening
measure: Adverse reactions
time frame: 48 weeks
description: Describe ART-related adverse events, and drug interactions
arm group label: Group A Immediate treatment (iART)
arm group type: Experimental
description: Other: time to start the ART within 48 hours of admission to hospitalization
arm group label: Group B Conventional treatment (cART)
arm group type: Active Comparator
description: Other: time to start the ART, after the opportunistic disease has been controlled, at the discretion of infectious disease specialist.
intervention type: Other
intervention name: iART
description: After group assignment, ART will be started within the first 48 hours after admission to the hospital. ART regimen will be decided according to each subject´s the clinical characteristics
arm group label: Group A Immediate treatment (iART)
intervention type: Other
intervention name: cART
description: After group assignment, ART is started at the discretion of the attending physician. ART regimen will be decided according to each subject´s the clinical characteristics
arm group label: Group B Conventional treatment (cART)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: GUSTAVO MD REYES-TERÁN, M.D.
role: Principal Investigator
affiliation: Instituto Nacional de Enfermedades Respiratorias
last name: GUSTAVO MD REYES-TERÁN, M.D.
phone: 56667985
phone ext: 100
email: gustavo.reyesteran@gmail.com
last name: Amy MD Peralta, M.D.
phone: 56667985
phone ext: 100
email: amy.peralta@cieni.org.mx
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
country: Mexico
responsible party type: Sponsor-Investigator
investigator affiliation: Centro de Investigación en. Enfermedades Infecciosas, Mexico
investigator full name: Gustavo Reyes-Teran
investigator title: Principal Investigator
mesh term: Acquired Immunodeficiency Syndrome
mesh term: HIV Infections