<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/NCT01679964</url>
  </required_header>
  <id_info>
    <org_study_id>MISP40301</org_study_id>
    <secondary_id>MISP 40301</secondary_id>
    <nct_id>NCT01679964</nct_id>
  </id_info>
  <brief_title>Sustained Virological Suppression and Improvement of Adverse Events of Switching to Raltegravir Study</brief_title>
  <acronym>TaISENWITCH</acronym>
  <official_title>A Single Arm Study to Assess the Sustained Virological Suppression and Improvement of Treatment-emerged Adverse Events of Switching to Raltegravir in Stable HIV-infected Patients on Ritonavir-boosted Protease Inhibitor Regimen</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lin, Hsi-Hsun, M.D.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lin, Hsi-Hsun, M.D.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Switching from the ritonavir-boosted protease inhibitor component to raltegravir in stable&#xD;
      HIV-infected adult patients receiving combination therapy will demonstrate improved clinical&#xD;
      tolerability or lipid profiles with sustained plasma virological response (&lt;50 copies/ml).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A. Objectives To compare the treatment-emerged AEs and virological suppression after switch&#xD;
      to raltegravir-based therapy in stable HIV-infected patients who receiving ritonavir-boosted&#xD;
      protease inhibitor antiretroviral regimen&#xD;
&#xD;
      Primary endpoints:&#xD;
&#xD;
      1) The changes in overall incidence and severity of patient-reported clinical adverse events&#xD;
      (based on &quot;symptom distress module) after switch to raltegravir-based therapy.&#xD;
&#xD;
      Secondary endpoints:&#xD;
&#xD;
        1. The proportion of patients who are free of &quot;virological failure&quot; at week 48 after switch&#xD;
&#xD;
        2. The change from baseline in CD4 cell counts at week 48 after switch&#xD;
&#xD;
        3. The change in quality of life by assess the changes in the domain scores of MOS-HIV&#xD;
           questionnaire at baseline and different study time points.&#xD;
&#xD;
        4. The changes in laboratory adverse event, e.g., the mean percent changes from baseline to&#xD;
           48 weeks in plasma lipid profile (total cholesterol, LDLCholesterol, HDL Cholesterol,&#xD;
           triglycerides) after switch&#xD;
&#xD;
        5. The proportion of patients who are free of &quot;treatment failure&quot; at week 48 after switch&#xD;
&#xD;
      Safety endpoints&#xD;
&#xD;
        1. Incidence of adverse events&#xD;
&#xD;
        2. The proportion of patients with treatment-related grade 3 or 4 adverse events and&#xD;
           laboratory abnormalities&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">February 2015</completion_date>
  <primary_completion_date type="Actual">February 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The proportion of patient-reported clinical adverse events</measure>
    <time_frame>Week 4, 12-16, 28-32, 48</time_frame>
    <description>The proportion of patient-reported clinical adverse events in total and by severity (based on symptom distress module) at 4 weeks, The proportion of patient-reported clinical adverse events in total and by severity (based on symptom distress module) at 12-16 weeks, The proportion of patient-reported clinical adverse events in total and by severity (based on symptom distress module) at 28-32 weeks, The proportion of patient-reported clinical adverse events in total and by severity (based on symptom distress module) at 48 weeks</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients who are free of &quot;virological failure&quot;</measure>
    <time_frame>Week 4, 12-16, 28-32, 48</time_frame>
    <description>The proportion of patients who are free of &quot;virological failure&quot; at week 4 after switch, The proportion of patients who are free of &quot;virological failure&quot; at week 12-16 after switch, The proportion of patients who are free of &quot;virological failure&quot; at week 28-32 after switch, The proportion of patients who are free of &quot;virological failure&quot; at week 48 after switch</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The change from baseline in CD4 cell counts</measure>
    <time_frame>Week 4, 12-16, 28-32, 48</time_frame>
    <description>The change from baseline in CD4 cell counts at week 4 after switch, The change from baseline in CD4 cell counts at week 12-16 after switch, The change from baseline in CD4 cell counts at week 28-32 after switch, The change from baseline in CD4 cell counts at week 48 after switch</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the change from baseline in life quality (based on the MOS-HIV questionnaire)</measure>
    <time_frame>week 12-16, 48</time_frame>
    <description>The change from baseline in quality of life (based on the MOS-HIV questionnaire) at week 12-16 after switch, The change from baseline in quality of life (based on the MOS-HIV questionnaire) at week 48 after switch.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides)</measure>
    <time_frame>Week 4, 12-16, 28-32, 48</time_frame>
    <description>The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 4 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 12-16 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 28-32 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 48 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients with treatment failure</measure>
    <time_frame>Week 4, 12-16, 28-32, 48</time_frame>
    <description>The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 4 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 12-16 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 28-32 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 48 weeks</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">107</enrollment>
  <condition>HIV Infection</condition>
  <condition>Adverse Drug Reaction</condition>
  <condition>Quality of Life</condition>
  <arm_group>
    <arm_group_label>Raltegravir switch</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Isentress (400mg) bid + 2 NRTI (at least 2 nucleoside or nucleotide reverse transcriptase inhibitors and no other protease inhibitors)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Raltegravir switch</intervention_name>
    <description>Isentress (400mg) bid + 2 NRTI (at least 2 nucleoside or nucleotide reverse transcriptase inhibitors and no other protease inhibitors)</description>
    <arm_group_label>Raltegravir switch</arm_group_label>
    <other_name>Isentress</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients who are infected with HIV-1&#xD;
&#xD;
          -  Ages at least 20 years&#xD;
&#xD;
          -  Patients are currently receiving a ritonavir-boosted PI-based regimen, including&#xD;
             lopinavir, atazanavir, or darunavir, plus at least 2 antiretroviral agents (NRTIs)&#xD;
&#xD;
          -  Patient complained of treatment-emerged clinical adverse events or abnormal lipid&#xD;
             profile&#xD;
&#xD;
          -  Patients with plasma HIV-1 viral RNA below 50 copies per ml for at least 6 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient with known history of contraindication or hypersensitivity to any component of&#xD;
             the study regimen&#xD;
&#xD;
          -  Patients with acute or decompensated chronic hepatitis in the previous 6 months&#xD;
&#xD;
          -  Patients with chronic hepatitis and serum aminotransferase concentrations are more&#xD;
             than 5 times the upper limit of the normal range&#xD;
&#xD;
          -  Patients with renal insufficiency (patients need dialysis or have serum creatinine&#xD;
             concentrations of more than twice the upper limit of the normal range&#xD;
&#xD;
          -  Current alcohol or substance abuse (patients receiving methadone for the management of&#xD;
             withdrawal symptoms due to substance abuse are allowed )&#xD;
&#xD;
          -  Patients have failed previous regimens (prior to starting the current 2NRTI+PI/r&#xD;
             regimen they are currently on)&#xD;
&#xD;
          -  Patient's viral load have not been consistently &lt;50 copies per ml for 6 months or&#xD;
             longer.&#xD;
&#xD;
          -  Patients initiated lipid lowering agents during the preceding 3 months&#xD;
&#xD;
          -  Patients with any medical disorder or history of any illness which, in the opinion of&#xD;
             the investigator, that the use of study medications is contraindicated or might&#xD;
             confound the results of the study or pose additional risk in administering study drugs&#xD;
             to the patient&#xD;
&#xD;
          -  Pregnant, wish to become pregnant during the study period or breastfeeding women&#xD;
&#xD;
          -  Patients who are lack of expectation to maintain assigned study medication during&#xD;
             study period&#xD;
&#xD;
          -  Patients who have received therapy with investigational drugs in the previous 3 months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hsi-Hsun Lin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>E-DA Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kaohsiung Medical University Chung-Ho Memorial Hospital</name>
      <address>
        <city>Kaohsiung</city>
        <zip>807</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>E-Da Hospital</name>
      <address>
        <city>Kaohsiung</city>
        <zip>824</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>China Medical University Hospital</name>
      <address>
        <city>Taichung</city>
        <zip>40447</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cheng Kung University Hospital</name>
      <address>
        <city>Tainan</city>
        <zip>704</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>10048</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei City Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>108</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chang Gung Memorial Hospital at Linkou</name>
      <address>
        <city>Taoyuan</city>
        <zip>333</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <reference>
    <citation>Walensky RP. The survival benefits of AIDS treatment in the US. J Infect Dis 2006;194:11-19 Lennox JL. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection. Lancet 2009;374:796-806 Steigbigel RT. Long-term efficacy and safety of Raltegravir combined with optimized background therapy in treatment-experienced patients with drug-resistant HIV infection. Clin Infect Dis 2010;50:605-12 Eron JJ. Switch to raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2). Lancet 2010;375:396-407 Martinex E. Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: the SPIRAL study. AIDS 2010, 24:1697-1707 Division of AIDS(DAIDS). Toxicity guideline for adults. http://rcc.tech-res.com/safetyand pharmacovigilance(accessed Apr 15, 2011)</citation>
  </reference>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>August 30, 2012</study_first_submitted>
  <study_first_submitted_qc>September 3, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 6, 2012</study_first_posted>
  <last_update_submitted>September 14, 2016</last_update_submitted>
  <last_update_submitted_qc>September 14, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 15, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV infection</keyword>
  <keyword>Raltegravir</keyword>
  <keyword>Adverse event</keyword>
  <keyword>Life quality</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>HIV Infections</mesh_term>
    <mesh_term>Drug-Related Side Effects and Adverse Reactions</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Raltegravir Potassium</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>December 8, 2016</submitted>
    <returned>January 31, 2017</returned>
  </pending_results>
  <!-- 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/NCT01679964
org study id: MISP40301
secondary id: MISP 40301
nct id: NCT01679964
lead sponsor: 
has dmc: No
Switching from the ritonavir-boosted protease inhibitor component to raltegravir in stable
      HIV-infected adult patients receiving combination therapy will demonstrate improved clinical
      tolerability or lipid profiles with sustained plasma virological response (<50 copies/ml).
A. Objectives To compare the treatment-emerged AEs and virological suppression after switch
      to raltegravir-based therapy in stable HIV-infected patients who receiving ritonavir-boosted
      protease inhibitor antiretroviral regimen

      Primary endpoints:

      1) The changes in overall incidence and severity of patient-reported clinical adverse events
      (based on "symptom distress module) after switch to raltegravir-based therapy.

      Secondary endpoints:

        1. The proportion of patients who are free of "virological failure" at week 48 after switch

        2. The change from baseline in CD4 cell counts at week 48 after switch

        3. The change in quality of life by assess the changes in the domain scores of MOS-HIV
           questionnaire at baseline and different study time points.

        4. The changes in laboratory adverse event, e.g., the mean percent changes from baseline to
           48 weeks in plasma lipid profile (total cholesterol, LDLCholesterol, HDL Cholesterol,
           triglycerides) after switch

        5. The proportion of patients who are free of "treatment failure" at week 48 after switch

      Safety endpoints

        1. Incidence of adverse events

        2. The proportion of patients with treatment-related grade 3 or 4 adverse events and
           laboratory abnormalities
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The proportion of patient-reported clinical adverse events
time frame: Week 4, 12-16, 28-32, 48
description: The proportion of patient-reported clinical adverse events in total and by severity (based on symptom distress module) at 4 weeks, The proportion of patient-reported clinical adverse events in total and by severity (based on symptom distress module) at 12-16 weeks, The proportion of patient-reported clinical adverse events in total and by severity (based on symptom distress module) at 28-32 weeks, The proportion of patient-reported clinical adverse events in total and by severity (based on symptom distress module) at 48 weeks
measure: The proportion of patients who are free of "virological failure"
time frame: Week 4, 12-16, 28-32, 48
description: The proportion of patients who are free of "virological failure" at week 4 after switch, The proportion of patients who are free of "virological failure" at week 12-16 after switch, The proportion of patients who are free of "virological failure" at week 28-32 after switch, The proportion of patients who are free of "virological failure" at week 48 after switch
measure: The change from baseline in CD4 cell counts
time frame: Week 4, 12-16, 28-32, 48
description: The change from baseline in CD4 cell counts at week 4 after switch, The change from baseline in CD4 cell counts at week 12-16 after switch, The change from baseline in CD4 cell counts at week 28-32 after switch, The change from baseline in CD4 cell counts at week 48 after switch
measure: the change from baseline in life quality (based on the MOS-HIV questionnaire)
time frame: week 12-16, 48
description: The change from baseline in quality of life (based on the MOS-HIV questionnaire) at week 12-16 after switch, The change from baseline in quality of life (based on the MOS-HIV questionnaire) at week 48 after switch.
measure: The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides)
time frame: Week 4, 12-16, 28-32, 48
description: The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 4 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 12-16 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 28-32 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 48 weeks
measure: The proportion of patients with treatment failure
time frame: Week 4, 12-16, 28-32, 48
description: The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 4 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 12-16 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 28-32 weeks, The percent changes from baseline in plasma lipid profiles (total cholesterol, LDL Cholesterol, HDL Cholesterol, triglycerides) at 48 weeks
arm group label: Raltegravir switch
arm group type: Other
description: Isentress (400mg) bid + 2 NRTI (at least 2 nucleoside or nucleotide reverse transcriptase inhibitors and no other protease inhibitors)
intervention type: Drug
intervention name: Raltegravir switch
description: Isentress (400mg) bid + 2 NRTI (at least 2 nucleoside or nucleotide reverse transcriptase inhibitors and no other protease inhibitors)
arm group label: Raltegravir switch
other name: Isentress
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Hsi-Hsun Lin, MD
role: Principal Investigator
affiliation: E-DA Hospital
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Taiwan
citation: Walensky RP. The survival benefits of AIDS treatment in the US. J Infect Dis 2006;194:11-19 Lennox JL. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection. Lancet 2009;374:796-806 Steigbigel RT. Long-term efficacy and safety of Raltegravir combined with optimized background therapy in treatment-experienced patients with drug-resistant HIV infection. Clin Infect Dis 2010;50:605-12 Eron JJ. Switch to raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2). Lancet 2010;375:396-407 Martinex E. Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: the SPIRAL study. AIDS 2010, 24:1697-1707 Division of AIDS(DAIDS). Toxicity guideline for adults. http://rcc.tech-res.com/safetyand pharmacovigilance(accessed Apr 15, 2011)
responsible party type: Sponsor
mesh term: HIV Infections
mesh term: Drug-Related Side Effects and Adverse Reactions
mesh term: Raltegravir Potassium
sharing ipd: No
submitted: December 8, 2016
returned: January 31, 2017