<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/NCT01733134</url>
  </required_header>
  <id_info>
    <org_study_id>ACTIVATE117</org_study_id>
    <nct_id>NCT01733134</nct_id>
  </id_info>
  <brief_title>Acute Heart Failure Patients With High Copeptin Treated With Tolvaptan Targets Increased AVP Activation for Treatment (ACTIVATE)</brief_title>
  <acronym>ACTIVATE</acronym>
  <official_title>Acute Heart Failure With High Copeptin Levels Treated With Tolvaptan Targets Increased AVP Activation for Treatment Efficacy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maisel, Alan, M.D.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Otsuka Pharmaceutical Development &amp; Commercialization, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Thermo Fisher Scientific, Inc</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Maisel, Alan, M.D.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients being hospitalized for acute heart failure and already receiving standard therapy&#xD;
      will be randomized to receive either tolvaptan or placebo, based on the level of copeptin&#xD;
      measured in their bloodstream. Patients with high copeptin levels will be able to participate&#xD;
      in the trial, patients with low levels will be excluded. Patients being admitted to the&#xD;
      observation unit for acute heart failure and already receiving standard therapy will be&#xD;
      randomized to receive either tolvaptan or placebo without consideration of the copeptin&#xD;
      level. The hypothesis is that patients receiving tolvaptan will have better improvement of&#xD;
      shortness of breath than those receiving placebo, within 9 hours of drug administration.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>January 2013</start_date>
  <completion_date type="Anticipated">December 2014</completion_date>
  <primary_completion_date type="Anticipated">June 2014</primary_completion_date>
  <phase>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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dyspnea</measure>
    <time_frame>9 hours</time_frame>
    <description>Dyspnea will be evaluated at 9 hours</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Length of stay</measure>
    <time_frame>during hospitalizaton</time_frame>
    <description>The length of hospitalization will be compared between the placebo and interventional cohorts</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rehospitalization</measure>
    <time_frame>30 days</time_frame>
    <description>The number and length of re-hospitalizations will be compared between the placebo and interventional cohorts</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">350</enrollment>
  <condition>Acute Heart Failure</condition>
  <arm_group>
    <arm_group_label>Standard therapy plus Tolvaptan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient in the interventional group will receive tolvaptan in addition to standard therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard therapy plus placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tolvaptan</intervention_name>
    <description>Tolvaptan 30 mg. tablet for subjects enrolled prior to first 8 hours of coming to an emergency department. Repeated daily up to 5th day.</description>
    <arm_group_label>Standard therapy plus Tolvaptan</arm_group_label>
    <other_name>Samsca</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Patient in the placebo group will receive tolvaptan in addition to standard therapy</description>
    <arm_group_label>Standard therapy plus placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Older than or equal to 18 years of age, with diagnosis and planned treatment for Acute&#xD;
             Heart Failure&#xD;
&#xD;
          2. Dyspnea at rest or minimal exertion per the patient&#xD;
&#xD;
          3. Evidence of extracellular volume expansion by at least one of the following: JVD,&#xD;
             Rales, Ascites, Edema or positive Chest X-ray defined as cardiomegaly, pulmonary&#xD;
             vascular congestion, Kerley B-lines, pulmonary edema and/or pleural effusion.&#xD;
&#xD;
          4. Elevated BNP level &gt;200 pg/ml, or NTproBNP &gt; 1000pg/mL&#xD;
&#xD;
          5. Able to administer study drug within 8 hours from triage time&#xD;
&#xD;
        Inpatient Hospitalized Inclusion Only:&#xD;
&#xD;
        Co-peptin level &gt; 27 pmol/L&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Unable to provide informed consent&#xD;
&#xD;
          2. Unable to have 30 day telephone follow up&#xD;
&#xD;
          3. Not expected to survive past 6 months&#xD;
&#xD;
          4. On Renal replacement therapy or creatinine &gt;3.5&#xD;
&#xD;
          5. History of allergy or intolerance to Tolvaptan&#xD;
&#xD;
          6. Suspected Pregnancy&#xD;
&#xD;
          7. Cardiogenic Shock&#xD;
&#xD;
          8. Participation in any interventional trial in prior 30 days.&#xD;
&#xD;
          9. Receiving or planned to receive IV Inotropic therapy&#xD;
&#xD;
         10. ACS now or in the past 30 days&#xD;
&#xD;
         11. Treatment with IV infusion vasoactive drugs in the hour prior to enrollment&#xD;
&#xD;
         12. Temperature &gt; 100.5&#xD;
&#xD;
         13. Heart Failure due to atrial fibrillation with Rapid Ventricular Response&#xD;
&#xD;
         14. SBP &lt; 90 mmHg&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alan S Maisel, MD</last_name>
    <role>Principal Investigator</role>
  </overall_official>
  <overall_contact>
    <last_name>Elizabeth B Gaul, RN</last_name>
    <phone>440-625-0499</phone>
    <email>comprehensiveresearch@gmail.com</email>
  </overall_contact>
  <verification_date>January 2013</verification_date>
  <study_first_submitted>November 20, 2012</study_first_submitted>
  <study_first_submitted_qc>November 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 26, 2012</study_first_posted>
  <last_update_submitted>January 17, 2013</last_update_submitted>
  <last_update_submitted_qc>January 17, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 18, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>acute heart failure</keyword>
  <keyword>emergency department</keyword>
  <keyword>copeptin</keyword>
  <keyword>adh antagonists</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Insipidus</mesh_term>
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tolvaptan</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01733134
org study id: ACTIVATE117
nct id: NCT01733134
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
Patients being hospitalized for acute heart failure and already receiving standard therapy
      will be randomized to receive either tolvaptan or placebo, based on the level of copeptin
      measured in their bloodstream. Patients with high copeptin levels will be able to participate
      in the trial, patients with low levels will be excluded. Patients being admitted to the
      observation unit for acute heart failure and already receiving standard therapy will be
      randomized to receive either tolvaptan or placebo without consideration of the copeptin
      level. The hypothesis is that patients receiving tolvaptan will have better improvement of
      shortness of breath than those receiving placebo, within 9 hours of drug administration.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Dyspnea
time frame: 9 hours
description: Dyspnea will be evaluated at 9 hours
measure: Length of stay
time frame: during hospitalizaton
description: The length of hospitalization will be compared between the placebo and interventional cohorts
measure: Rehospitalization
time frame: 30 days
description: The number and length of re-hospitalizations will be compared between the placebo and interventional cohorts
arm group label: Standard therapy plus Tolvaptan
arm group type: Experimental
description: Patient in the interventional group will receive tolvaptan in addition to standard therapy
arm group label: Standard therapy plus placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Tolvaptan
description: Tolvaptan 30 mg. tablet for subjects enrolled prior to first 8 hours of coming to an emergency department. Repeated daily up to 5th day.
arm group label: Standard therapy plus Tolvaptan
other name: Samsca
intervention type: Drug
intervention name: placebo
description: Patient in the placebo group will receive tolvaptan in addition to standard therapy
arm group label: Standard therapy plus placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alan S Maisel, MD
role: Principal Investigator
last name: Elizabeth B Gaul, RN
phone: 440-625-0499
email: comprehensiveresearch@gmail.com
responsible party type: Sponsor
mesh term: Diabetes Insipidus
mesh term: Heart Failure
mesh term: Tolvaptan