<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/NCT03019783</url>
  </required_header>
  <id_info>
    <org_study_id>AI424-469</org_study_id>
    <nct_id>NCT03019783</nct_id>
  </id_info>
  <brief_title>Atazanavir and Endothelial Function in Older HIV Patients</brief_title>
  <official_title>Atazanavir and Endothelial Function in Older HIV Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Brigham and Women's Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators hypothesize that older subjects with HIV randomly assigned to atazanavir&#xD;
      will have increased bilirubin levels, reduced oxidative stress, and improved flow-mediated,&#xD;
      endothelium-dependent vasodilation compared to subjects not switched to atazanavir.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The mortality induced by HIV has dropped significantly due to effective antiretroviral&#xD;
      therapy. Epidemiological data suggest a less than 5% 10-year mortality for patients treated&#xD;
      with HAART. As a result of the reduction in early AIDS-related deaths, HIV has become a&#xD;
      chronic disease manifesting the common components of chronic disease such as inflammation,&#xD;
      vascular dysfunction, and oxidative stress. The combination of these trends put HIV patients&#xD;
      at increased risk of myocardial infarction compared with age-matched subjects over the long&#xD;
      term. Several studies suggest that some protease inhibitors might increase the risk of&#xD;
      myocardial infarction. The leading theory behind this association derives from the&#xD;
      relationship between protease inhibitor use and the onset of an atherogenic dysmetabolism&#xD;
      including the development of insulin resistance, dyslipidemia, and oxidative stress.&#xD;
&#xD;
      In contrast to the older protease inhibitors, atazanavir induces neither insulin resistance&#xD;
      nor dyslipidemia. In addition, atazanavir has a property unique among protease inhibitors:&#xD;
      elevation of unconjugated bilirubin by inhibiting the enzyme uridine diphosphate&#xD;
      glucuronyltransferase (UGT) 1A1. Bilirubin is a potent intracellular antioxidant. The&#xD;
      investigators have demonstrated that higher levels of bilirubin within the normal range are&#xD;
      associated with reduced rates of stroke and peripheral artery disease. Patients with&#xD;
      Gilbert's Syndrome (chronic elevations of bilirubin as a result of genetically reduced UGT&#xD;
      1A1) have a lower rate of myocardial infarction compared with age-matched controls. It is&#xD;
      plausible that use of atazanavir compared with other protease inhibitors, by reducing&#xD;
      oxidative stress, may improve vascular function and, ultimately, reduce the rate of&#xD;
      cardiovascular complications with chronic therapy.&#xD;
&#xD;
      The benefit of atazanavir may be particularly important now with the aging of the HIV&#xD;
      population. Aging is associated with higher levels of oxidative stress and endothelial&#xD;
      dysfunction, both of which are associated with heightened rates of cardiovascular morbidity&#xD;
      and mortality. Accordingly, the investigators hypothesize that the use of atazanavir in&#xD;
      stable HIV patients age 45 years or older will improve endothelial dysfunction and reduce&#xD;
      oxidative stress compared with continuing the current therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2011</start_date>
  <completion_date type="Actual">June 2016</completion_date>
  <primary_completion_date type="Actual">June 2015</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Basic Science</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Flow-mediated, Endothelium-dependent Vasodilation</measure>
    <time_frame>4 weeks</time_frame>
    <description>The investigators will evaluate flow-mediated, brachial artery vasodilation (percentage increase in diameter in response to a 5 minute ischemic challenge) at study entry and then after 28 days, with the change between the two measurements being the primary endpoint.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Plasma Total Antioxidant Capacity</measure>
    <time_frame>4 weeks</time_frame>
    <description>The investigators will evaluate plasma total antioxidant capacity at study entry and then after 28 days, with the change between the two measurements being the secondary endpoint.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>HIV</condition>
  <arm_group>
    <arm_group_label>Remains on baseline HIV regimen</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects are enrolled and either kept on their baseline regimen. This is being designated the placebo comparator.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Atazanavir switch</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>These subjects are switched to an atazanavir-based regimen.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atazanavir</intervention_name>
    <description>The active group will switch from a non-atazanavir regimen to an atazanavir-based regimen.</description>
    <arm_group_label>Atazanavir switch</arm_group_label>
    <other_name>Reyataz</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The control group will stay on their baseline regimen</description>
    <arm_group_label>Remains on baseline HIV regimen</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 45 years&#xD;
&#xD;
          -  Stable non-atazanavir-containing regimen consisting of co-formulated&#xD;
             tenofovir/emtricitabine as the NRTIs plus a third agent for 3 months or longer. The&#xD;
             third agent can be any FDA-approved PI, NNRTI, or raltegravir.&#xD;
&#xD;
          -  HIV RNA &lt; 200 cop/mL at screening and at least once within the prior year,&#xD;
&#xD;
          -  No treatment interruptions &gt; 7 days in the 3 months prior to study entry&#xD;
&#xD;
          -  The ability to understand and sign a written informed consent form, which must be&#xD;
             obtained prior to initiation of study procedures.&#xD;
&#xD;
          -  Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)&#xD;
&#xD;
          -  Signed Written Informed Consent. Before any study procedures are performed, subjects&#xD;
             will have the details of the study described to them, and they will be given a written&#xD;
             informed consent document to read. Then, if subjects consent to participate in the&#xD;
             study, they will indicate that consent by signing and dating the informed consent&#xD;
             document in the presence of study personnel.&#xD;
&#xD;
          -  Women of childbearing potential (WOCBP) must be using an adequate method of&#xD;
             contraception to avoid pregnancy throughout the study and for up to 4 weeks after the&#xD;
             last dose of study drug to minimize the risk of pregnancy.&#xD;
&#xD;
          -  WOCBP include any woman who has experienced menarche and who has not undergone&#xD;
             successful surgical sterilization (hysterectomy, bilateral tubal ligation, or&#xD;
             bilateral oophorectomy) or who is not post-menopausal. Post-menopause is defined as:&#xD;
&#xD;
               -  Amenorrhea that has lasted for 12 consecutive months without another cause, or&#xD;
&#xD;
               -  For women with irregular menstrual periods who are taking hormone replacement&#xD;
                  therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of&#xD;
                  greater than 35 mIU/mL.&#xD;
&#xD;
               -  Women who are using oral contraceptives, other hormonal contraceptives (vaginal&#xD;
                  products, skin patches, or implanted or injectable products), or mechanical&#xD;
                  products such as an intrauterine device or barrier methods (diaphragm, condoms,&#xD;
                  spermicides) to prevent pregnancy, or who are practicing abstinence or where&#xD;
                  their partner is sterile (eg, vasectomy) should be considered to be of&#xD;
                  childbearing potential.&#xD;
&#xD;
               -  WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25&#xD;
                  IU/L or equivalent units of HCG) within 72 hours before the start of the&#xD;
                  investigational product.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Sex and Reproductive Status&#xD;
&#xD;
               -  WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy&#xD;
                  for the entire study period and for up to 4 weeks after the last dose of study&#xD;
                  drug.&#xD;
&#xD;
               -  Women who are pregnant or breastfeeding.&#xD;
&#xD;
               -  Women with a positive pregnancy test.&#xD;
&#xD;
          -  Target Disease Exceptions&#xD;
&#xD;
               -  Prior treatment failure on or intolerance to atazanavir&#xD;
&#xD;
               -  Known or suspected resistance to atazanavir&#xD;
&#xD;
               -  Receiving ART different from co-formulated tenofovir/emtricitabine plus third&#xD;
                  agent (PI, NNRTI, or raltegravir) regimen&#xD;
&#xD;
               -  Receiving Viagra, Levitra, or Cialis&#xD;
&#xD;
               -  A new AIDS-defining condition diagnosed within the 30 days prior to screening&#xD;
&#xD;
               -  Active, serious infections (other than HIV-1 infection) requiring parenteral&#xD;
                  antibiotic or antifungal therapy within 30 days prior to baseline&#xD;
&#xD;
          -  Medical History and Concurrent Diseases&#xD;
&#xD;
               -  Patients with Gilbert's Syndrome or elevated bilirubin levels (&gt;1.5 mg/dL) at&#xD;
                  baseline (for the randomized trial)&#xD;
&#xD;
               -  Patients with uncontrolled diabetes (hemoglobin A1c &gt; 11%)&#xD;
&#xD;
               -  Patients allergic to nitroglycerin&#xD;
&#xD;
          -  Prohibited Treatments and/or Therapies&#xD;
&#xD;
               -  Recent initiation of hormones or immunomodulators (3 months)&#xD;
&#xD;
               -  Current receipt of proton-pump inhibitor therapy&#xD;
&#xD;
          -  Other Exclusion Criteria&#xD;
&#xD;
               -  Prisoners, or subjects who are involuntarily incarcerated.&#xD;
&#xD;
               -  Subjects who are compulsorily detained for treatment of either a psychiatric or&#xD;
                  physical (eg, infectious disease) illness.&#xD;
&#xD;
               -  Subjects for whom the investigators believe there will be a low likelihood of&#xD;
                  medication compliance.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joshua Beckman</last_name>
    <role>Principal Investigator</role>
    <affiliation>Brigham and Women's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>December 8, 2016</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 13, 2017</study_first_posted>
  <results_first_submitted>March 7, 2017</results_first_submitted>
  <results_first_submitted_qc>March 7, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">April 18, 2017</results_first_posted>
  <last_update_submitted>April 17, 2017</last_update_submitted>
  <last_update_submitted_qc>April 17, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 16, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brigham and Women's Hospital</investigator_affiliation>
    <investigator_full_name>Joshua A. Beckman, MD</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Endothelial function</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atazanavir Sulfate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Remains on Baseline HIV Regimen</title>
          <description>Subjects are enrolled and either kept on their baseline regimen. This is being designated the placebo comparator.&#xD;
Placebo: The control group will stay on their baseline regimen</description>
        </group>
        <group group_id="P2">
          <title>Atazanavir Switch</title>
          <description>These subjects are switched to an atazanavir-based regimen.&#xD;
Atazanavir: The active group will switch from a non-atazanavir regimen to an atazanavir-based regimen.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Remains on Baseline HIV Regimen</title>
          <description>Subjects are enrolled and either kept on their baseline regimen. This is being designated the placebo comparator.&#xD;
Placebo: The control group will stay on their baseline regimen</description>
        </group>
        <group group_id="B2">
          <title>Atazanavir Switch</title>
          <description>These subjects are switched to an atazanavir-based regimen.&#xD;
Atazanavir: The active group will switch from a non-atazanavir regimen to an atazanavir-based regimen.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="29"/>
            <count group_id="B2" value="31"/>
            <count group_id="B3" value="60"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="53" spread="6"/>
                    <measurement group_id="B2" value="53" spread="6"/>
                    <measurement group_id="B3" value="53" spread="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Flow-mediated, Endothelium-dependent Vasodilation</title>
        <description>The investigators will evaluate flow-mediated, brachial artery vasodilation (percentage increase in diameter in response to a 5 minute ischemic challenge) at study entry and then after 28 days, with the change between the two measurements being the primary endpoint.</description>
        <time_frame>4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Remains on Baseline HIV Regimen</title>
            <description>Subjects are enrolled and either kept on their baseline regimen. This is being designated the placebo comparator.&#xD;
Placebo: The control group will stay on their baseline regimen</description>
          </group>
          <group group_id="O2">
            <title>Atazanavir Switch</title>
            <description>These subjects are switched to an atazanavir-based regimen.&#xD;
Atazanavir: The active group will switch from a non-atazanavir regimen to an atazanavir-based regimen.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Flow-mediated, Endothelium-dependent Vasodilation</title>
          <description>The investigators will evaluate flow-mediated, brachial artery vasodilation (percentage increase in diameter in response to a 5 minute ischemic challenge) at study entry and then after 28 days, with the change between the two measurements being the primary endpoint.</description>
          <units>percentage vasodilation</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2" spread="2.4"/>
                    <measurement group_id="O2" value="0.8" spread="4.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Plasma Total Antioxidant Capacity</title>
        <description>The investigators will evaluate plasma total antioxidant capacity at study entry and then after 28 days, with the change between the two measurements being the secondary endpoint.</description>
        <time_frame>4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Remains on Baseline HIV Regimen</title>
            <description>Subjects are enrolled and either kept on their baseline regimen. This is being designated the placebo comparator.&#xD;
Placebo: The control group will stay on their baseline regimen</description>
          </group>
          <group group_id="O2">
            <title>Atazanavir Switch</title>
            <description>These subjects are switched to an atazanavir-based regimen.&#xD;
Atazanavir: The active group will switch from a non-atazanavir regimen to an atazanavir-based regimen.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Plasma Total Antioxidant Capacity</title>
          <description>The investigators will evaluate plasma total antioxidant capacity at study entry and then after 28 days, with the change between the two measurements being the secondary endpoint.</description>
          <units>micromolar</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="31"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-21" spread="271"/>
                    <measurement group_id="O2" value="219" spread="213"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 month</time_frame>
      <desc>No adverse events</desc>
      <group_list>
        <group group_id="E1">
          <title>Remains on Baseline HIV Regimen</title>
          <description>Subjects are enrolled and either kept on their baseline regimen. This is being designated the placebo comparator.&#xD;
Placebo: The control group will stay on their baseline regimen</description>
        </group>
        <group group_id="E2">
          <title>Atazanavir Switch</title>
          <description>These subjects are switched to an atazanavir-based regimen.&#xD;
Atazanavir: The active group will switch from a non-atazanavir regimen to an atazanavir-based regimen.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="31"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>There were no limitations.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Joshua Beckman</name_or_title>
      <organization>Brigham and Women's Hospital</organization>
      <phone>617-732-5500</phone>
      <email>joshua.a.beckman@vanderbilt.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03019783
org study id: AI424-469
nct id: NCT03019783
lead sponsor: 
has dmc: No
The investigators hypothesize that older subjects with HIV randomly assigned to atazanavir
      will have increased bilirubin levels, reduced oxidative stress, and improved flow-mediated,
      endothelium-dependent vasodilation compared to subjects not switched to atazanavir.
The mortality induced by HIV has dropped significantly due to effective antiretroviral
      therapy. Epidemiological data suggest a less than 5% 10-year mortality for patients treated
      with HAART. As a result of the reduction in early AIDS-related deaths, HIV has become a
      chronic disease manifesting the common components of chronic disease such as inflammation,
      vascular dysfunction, and oxidative stress. The combination of these trends put HIV patients
      at increased risk of myocardial infarction compared with age-matched subjects over the long
      term. Several studies suggest that some protease inhibitors might increase the risk of
      myocardial infarction. The leading theory behind this association derives from the
      relationship between protease inhibitor use and the onset of an atherogenic dysmetabolism
      including the development of insulin resistance, dyslipidemia, and oxidative stress.

      In contrast to the older protease inhibitors, atazanavir induces neither insulin resistance
      nor dyslipidemia. In addition, atazanavir has a property unique among protease inhibitors:
      elevation of unconjugated bilirubin by inhibiting the enzyme uridine diphosphate
      glucuronyltransferase (UGT) 1A1. Bilirubin is a potent intracellular antioxidant. The
      investigators have demonstrated that higher levels of bilirubin within the normal range are
      associated with reduced rates of stroke and peripheral artery disease. Patients with
      Gilbert's Syndrome (chronic elevations of bilirubin as a result of genetically reduced UGT
      1A1) have a lower rate of myocardial infarction compared with age-matched controls. It is
      plausible that use of atazanavir compared with other protease inhibitors, by reducing
      oxidative stress, may improve vascular function and, ultimately, reduce the rate of
      cardiovascular complications with chronic therapy.

      The benefit of atazanavir may be particularly important now with the aging of the HIV
      population. Aging is associated with higher levels of oxidative stress and endothelial
      dysfunction, both of which are associated with heightened rates of cardiovascular morbidity
      and mortality. Accordingly, the investigators hypothesize that the use of atazanavir in
      stable HIV patients age 45 years or older will improve endothelial dysfunction and reduce
      oxidative stress compared with continuing the current therapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change in Flow-mediated, Endothelium-dependent Vasodilation
time frame: 4 weeks
description: The investigators will evaluate flow-mediated, brachial artery vasodilation (percentage increase in diameter in response to a 5 minute ischemic challenge) at study entry and then after 28 days, with the change between the two measurements being the primary endpoint.
measure: Change in Plasma Total Antioxidant Capacity
time frame: 4 weeks
description: The investigators will evaluate plasma total antioxidant capacity at study entry and then after 28 days, with the change between the two measurements being the secondary endpoint.
arm group label: Remains on baseline HIV regimen
arm group type: Placebo Comparator
description: Subjects are enrolled and either kept on their baseline regimen. This is being designated the placebo comparator.
arm group label: Atazanavir switch
arm group type: Active Comparator
description: These subjects are switched to an atazanavir-based regimen.
intervention type: Drug
intervention name: Atazanavir
description: The active group will switch from a non-atazanavir regimen to an atazanavir-based regimen.
arm group label: Atazanavir switch
other name: Reyataz
intervention type: Other
intervention name: Placebo
description: The control group will stay on their baseline regimen
arm group label: Remains on baseline HIV regimen
criteria: 
gender: All
minimum age: 45 Years
maximum age: N/A
healthy volunteers: No
last name: Joshua Beckman
role: Principal Investigator
affiliation: Brigham and Women's Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Joshua A. Beckman, MD
investigator title: Associate Professor of Medicine
mesh term: Atazanavir Sulfate
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: There were no limitations.
point of contact: 