<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/NCT02232880</url>
  </required_header>
  <id_info>
    <org_study_id>121740</org_study_id>
    <nct_id>NCT02232880</nct_id>
  </id_info>
  <brief_title>Treatment of Resistant Hypertension by Prevention of T-Cell Co-Stimulation</brief_title>
  <official_title>Treatment of Resistant Hypertension by Prevention of T-Cell Co-Stimulation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Vanderbilt University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to test whether abatacept, a drug approved by the Food and Drug&#xD;
      Administration to treat rheumatoid arthritis, may help blood pressure medications to work&#xD;
      better. This will be studied in people with high blood pressure that is not well controlled&#xD;
      on three or more blood pressure medications, the condition also known as resistant&#xD;
      hypertension. We expect to show that adding abatacept therapy to standardized treatment of&#xD;
      resistant hypertension will result in a greater decrease in blood pressure at 24 weeks&#xD;
      compared to treatment with placebo and conventional blood pressure treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    failure to recruit&#xD;
  </why_stopped>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">June 2015</completion_date>
  <primary_completion_date type="Actual">June 2015</primary_completion_date>
  <phase>Phase 2</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Systolic Blood Pressure From Randomization to End of Treatment</measure>
    <time_frame>6 months</time_frame>
    <description>Ambulatory blood pressure monitoring will be used at the end of the 4 weeks standardized treatment and at the end of 6 months randomized treatment with abatacept or placebo. The change in systolic blood pressure from these 2 recordings will be the primary endpoint.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Blood Pressure</measure>
    <time_frame>6 months</time_frame>
    <description>Changes in the rate of change of blood pressure estimated by automated in office cuff measurements and ambulatory blood pressure at 12 weeks after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Brachial Artery Reactivity</measure>
    <time_frame>6 months</time_frame>
    <description>change in brachial artery reactivity measured at randomization and after 24 weeks of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Inflammatory Markers</measure>
    <time_frame>6 months</time_frame>
    <description>changes in plasma and T cell markers of activation and T cell cytokine production from randomization to end of 24 weeks of treatment</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>abatacept</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects randomized to abatacept weighing 60 to 100 kg will receive 750 mg, and those &gt;100 kg will receive 1000 mg abatacept by intravenous infusion at 0 [randomization], 2, and 4 weeks and then every 4 weeks thereafter for a total of 24 weeks.&#xD;
All subjects will be treated with chlorthalidone 25 mg/day, lisinopril 20 mg/day [Patients with a history of adverse reaction to lisinopril will be treated with losartan 50 mg/day], amlodipine 5 mg/day and spironolactone 25 mg bid as standardized treatment of hypertension prior to randomization and throughout the active treatment phase.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects randomized to placebo will receive 100 ml normal saline by intravenous infusion at 0 [randomization], 2, and 4 weeks and then every 4 weeks thereafter for a total of 24 weeks.&#xD;
All subjects will be treated with chlorthalidone 25 mg/day, lisinopril 20 mg/day [Patients with a history of adverse reaction to lisinopril will be treated with losartan 50 mg/day], amlodipine 5 mg/day and spironolactone 25 mg bid as standardized treatment of hypertension prior to randomization and throughout the active treatment phase.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Abatacept</intervention_name>
    <description>All subjects will be treated with chlorthalidone 25 mg/day, lisinopril 20 mg/day [Patients with a history of adverse reaction to lisinopril will be treated with losartan 50 mg/day], amlodipine 5 mg/day and spironolactone 25 mg bid as standardized treatment of hypertension prior to randomization and throughout the active treatment phase.</description>
    <arm_group_label>abatacept</arm_group_label>
    <other_name>Orencia</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>All subjects will be treated with chlorthalidone 25 mg/day, lisinopril 20 mg/day [Patients with a history of adverse reaction to lisinopril will be treated with losartan 50 mg/day], amlodipine 5 mg/day and spironolactone 25 mg bid as standardized treatment of hypertension prior to randomization and throughout the active treatment phase.</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women 18 to 65 years of age with hypertension, treated with three or more&#xD;
             anti-hypertensive drugs, one being a diuretic, and&#xD;
&#xD;
          -  having a systolic blood pressure &gt;150 mmHg in the clinic and daytime average &gt;150 mmHg&#xD;
             on ambulatory blood pressure monitoring&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Medical history of secondary cause of hypertension, severe obesity (BMI &gt;35), severe&#xD;
             psychiatric disorders, cancer in the last 5 years other than nonmelanoma skin cell&#xD;
             cancers, herpes zoster or cytomegalovirus that resolved less than 2 months before&#xD;
&#xD;
          -  Inability to return for abatacept treatment and follow-up for 24 weeks.&#xD;
&#xD;
          -  Inability to understand or complete study-related assessments.&#xD;
&#xD;
          -  Current abuse of drugs or alcohol.&#xD;
&#xD;
          -  Receipt of any live vaccines within 3 months of the anticipated first dose of study&#xD;
             medication.&#xD;
&#xD;
          -  Evidence of active or latent bacterial or viral infections at the time of potential&#xD;
             enrollment, including human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Risk for tuberculosis&#xD;
&#xD;
          -  Abnormal laboratory values including positive hepatitis B surface antigen, hemoglobin&#xD;
             &lt; 8.5 g/dL, white blood cell count &lt; 3000/mm3, platelets &lt; 100,000/mm3, creatinine &gt;&#xD;
             2.5 times the upper limit of normal (ULN), alanine aminotransferase or aspartate&#xD;
             aminotransferase &gt; 2 times the ULN.&#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>David G Harrison, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232-6602</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>August 12, 2014</study_first_submitted>
  <study_first_submitted_qc>September 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2014</study_first_posted>
  <results_first_submitted>July 14, 2016</results_first_submitted>
  <results_first_submitted_qc>July 14, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">August 29, 2016</results_first_posted>
  <last_update_submitted>December 14, 2016</last_update_submitted>
  <last_update_submitted_qc>December 14, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 7, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>hypertension</keyword>
  <keyword>inflammation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Abatacept</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>One participant was consented. The study terminated before the participant was randomized. No participants received treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Consented Patients</title>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>study stopped prior to randomization</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Consented Patients</title>
          <description>No patients received treatment prior to study termination</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Gender</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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" 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="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Systolic Blood Pressure From Randomization to End of Treatment</title>
        <description>Ambulatory blood pressure monitoring will be used at the end of the 4 weeks standardized treatment and at the end of 6 months randomized treatment with abatacept or placebo. The change in systolic blood pressure from these 2 recordings will be the primary endpoint.</description>
        <time_frame>6 months</time_frame>
        <population>No patients received treatment prior to study termination</population>
        <group_list>
          <group group_id="O1">
            <title>Consented Patients</title>
          </group>
        </group_list>
        <measure>
          <title>Change in Systolic Blood Pressure From Randomization to End of Treatment</title>
          <description>Ambulatory blood pressure monitoring will be used at the end of the 4 weeks standardized treatment and at the end of 6 months randomized treatment with abatacept or placebo. The change in systolic blood pressure from these 2 recordings will be the primary endpoint.</description>
          <population>No patients received treatment prior to study termination</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Blood Pressure</title>
        <description>Changes in the rate of change of blood pressure estimated by automated in office cuff measurements and ambulatory blood pressure at 12 weeks after randomization</description>
        <time_frame>6 months</time_frame>
        <population>No patients received treatment prior to study termination.</population>
        <group_list>
          <group group_id="O1">
            <title>Consented Patients</title>
          </group>
        </group_list>
        <measure>
          <title>Change in Blood Pressure</title>
          <description>Changes in the rate of change of blood pressure estimated by automated in office cuff measurements and ambulatory blood pressure at 12 weeks after randomization</description>
          <population>No patients received treatment prior to study termination.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Brachial Artery Reactivity</title>
        <description>change in brachial artery reactivity measured at randomization and after 24 weeks of treatment</description>
        <time_frame>6 months</time_frame>
        <population>No patients received treatment prior to study termination</population>
        <group_list>
          <group group_id="O1">
            <title>Consented Patients</title>
          </group>
        </group_list>
        <measure>
          <title>Change in Brachial Artery Reactivity</title>
          <description>change in brachial artery reactivity measured at randomization and after 24 weeks of treatment</description>
          <population>No patients received treatment prior to study termination</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Inflammatory Markers</title>
        <description>changes in plasma and T cell markers of activation and T cell cytokine production from randomization to end of 24 weeks of treatment</description>
        <time_frame>6 months</time_frame>
        <population>No patients received treatment prior to study termination</population>
        <group_list>
          <group group_id="O1">
            <title>Consented Patients</title>
          </group>
        </group_list>
        <measure>
          <title>Change in Inflammatory Markers</title>
          <description>changes in plasma and T cell markers of activation and T cell cytokine production from randomization to end of 24 weeks of treatment</description>
          <population>No patients received treatment prior to study termination</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <desc>One participant was consented. The study terminated before the participant was randomized. No participants received treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Consented Patients</title>
          <description>No patients received treatment prior to study termination</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
              </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="1"/>
              </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>No patients received treatment prior to study termination.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>David Harrison</name_or_title>
      <organization>Vanderbilt University</organization>
      <email>david.g.harrison@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/NCT02232880
org study id: 121740
nct id: NCT02232880
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to test whether abatacept, a drug approved by the Food and Drug
      Administration to treat rheumatoid arthritis, may help blood pressure medications to work
      better. This will be studied in people with high blood pressure that is not well controlled
      on three or more blood pressure medications, the condition also known as resistant
      hypertension. We expect to show that adding abatacept therapy to standardized treatment of
      resistant hypertension will result in a greater decrease in blood pressure at 24 weeks
      compared to treatment with placebo and conventional blood pressure treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change in Systolic Blood Pressure From Randomization to End of Treatment
time frame: 6 months
description: Ambulatory blood pressure monitoring will be used at the end of the 4 weeks standardized treatment and at the end of 6 months randomized treatment with abatacept or placebo. The change in systolic blood pressure from these 2 recordings will be the primary endpoint.
measure: Change in Blood Pressure
time frame: 6 months
description: Changes in the rate of change of blood pressure estimated by automated in office cuff measurements and ambulatory blood pressure at 12 weeks after randomization
measure: Change in Brachial Artery Reactivity
time frame: 6 months
description: change in brachial artery reactivity measured at randomization and after 24 weeks of treatment
measure: Change in Inflammatory Markers
time frame: 6 months
description: changes in plasma and T cell markers of activation and T cell cytokine production from randomization to end of 24 weeks of treatment
arm group label: abatacept
arm group type: Active Comparator
description: Subjects randomized to abatacept weighing 60 to 100 kg will receive 750 mg, and those >100 kg will receive 1000 mg abatacept by intravenous infusion at 0 [randomization], 2, and 4 weeks and then every 4 weeks thereafter for a total of 24 weeks.
All subjects will be treated with chlorthalidone 25 mg/day, lisinopril 20 mg/day [Patients with a history of adverse reaction to lisinopril will be treated with losartan 50 mg/day], amlodipine 5 mg/day and spironolactone 25 mg bid as standardized treatment of hypertension prior to randomization and throughout the active treatment phase.
arm group label: placebo
arm group type: Placebo Comparator
description: Subjects randomized to placebo will receive 100 ml normal saline by intravenous infusion at 0 [randomization], 2, and 4 weeks and then every 4 weeks thereafter for a total of 24 weeks.
All subjects will be treated with chlorthalidone 25 mg/day, lisinopril 20 mg/day [Patients with a history of adverse reaction to lisinopril will be treated with losartan 50 mg/day], amlodipine 5 mg/day and spironolactone 25 mg bid as standardized treatment of hypertension prior to randomization and throughout the active treatment phase.
intervention type: Drug
intervention name: Abatacept
description: All subjects will be treated with chlorthalidone 25 mg/day, lisinopril 20 mg/day [Patients with a history of adverse reaction to lisinopril will be treated with losartan 50 mg/day], amlodipine 5 mg/day and spironolactone 25 mg bid as standardized treatment of hypertension prior to randomization and throughout the active treatment phase.
arm group label: abatacept
other name: Orencia
intervention type: Drug
intervention name: Placebo
description: All subjects will be treated with chlorthalidone 25 mg/day, lisinopril 20 mg/day [Patients with a history of adverse reaction to lisinopril will be treated with losartan 50 mg/day], amlodipine 5 mg/day and spironolactone 25 mg bid as standardized treatment of hypertension prior to randomization and throughout the active treatment phase.
arm group label: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: David G Harrison, MD
role: Principal Investigator
affiliation: Vanderbilt University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hypertension
mesh term: Abatacept
sharing ipd: Undecided
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: No patients received treatment prior to study termination.
point of contact: 