<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/NCT01661634</url>
  </required_header>
  <id_info>
    <org_study_id>ULA01</org_study_id>
    <secondary_id>2010-024249-59</secondary_id>
    <nct_id>NCT01661634</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Ularitide for the Treatment of Acute Decompensated Heart Failure</brief_title>
  <acronym>TRUE-AHF</acronym>
  <official_title>Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Ularitide (Urodilatin) Intravenous Infusion in Patients Suffering From Acute Decompensated Heart Failure [TRUE-AHF]</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cardiorentis</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Quintiles, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Cardiorentis</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the efficacy and safety of a continuous intravenous&#xD;
      (IV) ularitide infusion on the clinical status and outcome of patients with acute&#xD;
      decompensated heart failure (ADHF).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objective of the TRUE-AHF study is to evaluate the effect of a 48-h continuous IV&#xD;
      infusion of ularitide (15 ng/kg/min) versus placebo on the clinical status of patients with&#xD;
      acute decompensated heart failure (ADHF).&#xD;
&#xD;
      The study drug will be administered in addition to the standard treatment. The nature of&#xD;
      standard therapy will be carried out according to the clinical judgment of the Investigator&#xD;
      and may include vasodilator, inotropic, and diuretic drugs, as clinically indicated.&#xD;
&#xD;
      There are two co-primary endpoints for this study. Co-primary endpoint 1 will be a&#xD;
      hierarchical clinical composite variable that includes a patient-centered assessment of&#xD;
      clinical progress, an assessment of lack of improvement or worsening of HF requiring a&#xD;
      pre-specified intervention, and death.&#xD;
&#xD;
      The endpoint is intended to mimic the assessment that would be carried out by a physician&#xD;
      caring for the patient. If, during the 48 h infusion, a patient's clinical course&#xD;
      deteriorates because he/she dies, fails to improve or develops worsening HF requiring a&#xD;
      pre-specified intervention or if the patient considers his/her general clinical status as&#xD;
      moderately or markedly worse, the patient will be considered to be &quot;worse&quot;. If the patient&#xD;
      considers his/her general clinical status as moderately or markedly improved and if such&#xD;
      improvement is sustained without fulfilling the criteria for &quot;worse&quot; throughout the 48-h&#xD;
      infusion (from 0 h to 48 h), the patient will be considered to be &quot;improved&quot;. If the patient&#xD;
      is neither improved nor worse, the patient's clinical status will be considered to be&#xD;
      &quot;unchanged&quot;.&#xD;
&#xD;
      Co-primary efficacy endpoint 2 evaluates freedom from cardiovascular mortality during follow&#xD;
      up after randomization, for the entire duration of the trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">March 2016</completion_date>
  <primary_completion_date type="Actual">November 2015</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>Two Co-primary Efficacy Endpoints</measure>
    <time_frame>6, 24, 48 hours post infusion through the entire duration of the trial</time_frame>
    <description>Improvement in a hierarchical clinical composite comprised of elements associated with: patient global assessment using a 7-point scale of symptomatic improvement, lack of improvement, or worsening; persistent or worsening heart failure (HF) requiring an intervention (initiation or intensification of IV therapy, circulatory or ventilatory mechanical support, surgical intervention, ultrafiltration, hemofiltration or dialysis); and all-cause mortality. Assessment of the clinical composite will be performed at 6 hour (h), 24 h and 48 h after start of IV ularitide infusion&#xD;
Freedom from cardiovascular mortality during follow up after randomization, for the entire duration of the trial.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Length of stay of index hospitalization in hours after start of study drug infusion</measure>
    <time_frame>up to 30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of stay in intensive care (intensive care unit [ICU] or critical care unit [CCU])</measure>
    <time_frame>during the first 120 h following the start of the study drug infusion.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of events of persistent or worsening HF requiring an intervention</measure>
    <time_frame>from the start of the study drug infusion to 120 h.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with persistent or worsening HF and requiring an intervention</measure>
    <time_frame>from the start of study drug infusion to 120 h.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction in rehospitalization for heart failure</measure>
    <time_frame>within 30 days after initial hospital</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of N-terminal pro brain natriuretic peptide (NT-pro BNP)</measure>
    <time_frame>48 h of treatment compared to baseline.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to completion of last dose of any IV drugs that can be used for the treatment of HF (e.g., diuretics, vasodilators, or positive inotropic agents)</measure>
    <time_frame>for the first 120 h following the start of the drug infusion.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum creatinine</measure>
    <time_frame>from baseline through 72 h.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>180 days after start of study drug infusion, including patients still hospitalized at Day 30.</measure>
    <time_frame>All-cause mortality and cardiovascular rehospitalization</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">2157</enrollment>
  <condition>Acute Decompensated Heart Failure</condition>
  <arm_group>
    <arm_group_label>Ularitide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ularitide, lyophilizate for i.v. infusion, 15 ng/kg BW/min, for 48 hours</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo lyophilizate for i.v. infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ularitide</intervention_name>
    <arm_group_label>Ularitide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males and females aged 18 to 85 years.&#xD;
&#xD;
          2. Unplanned hospitalization or emergency department visit for ADHF. Acute HF is defined&#xD;
             as including all of the following:&#xD;
&#xD;
               -  Dyspnea at rest in a recumbent sitting position (30 to 45 degrees), which has&#xD;
                  worsened within the past week;&#xD;
&#xD;
               -  Radiological evidence of HF on a chest X-ray (if an appropriate chest;&#xD;
&#xD;
               -  computerized tomography scan is done; the X-ray need not be performed);&#xD;
&#xD;
               -  Brain natriuretic peptide (BNP) &gt;500 pg/mL or NT-pro BNP &gt;2000 pg/mL.&#xD;
&#xD;
          3. Ability to start infusion of the study drug within 12 h after initial clinical&#xD;
             assessment.&#xD;
&#xD;
          4. Ability to reliably carry out self-assessment of symptoms.&#xD;
&#xD;
          5. Systolic blood pressure ≥116 mmHg and ≤180 mmHg at the time of randomization.&#xD;
&#xD;
          6. Persisting dyspnea at rest despite standard background therapy for ADHF (as determined&#xD;
             by the Investigator) which must include IV furosemide (or equivalent diuretic) at ≥40&#xD;
             mg (or its equivalent) at any time after start of emergency services (ambulance,&#xD;
             emergency department, or hospital). At the time of randomization, the patient must&#xD;
             still be symptomatic. In addition, the patient should not have received an IV bolus of&#xD;
             a diuretic for at least 2 h prior to randomization, and the infusion rates of all&#xD;
             ongoing IV infusions of medications to treat HF must not have been increased or&#xD;
             decreased for at least 2 h prior to randomization.&#xD;
&#xD;
          7. Ability to understand the purpose and risks of the study and provide signed and dated&#xD;
             informed consent and authorization to use protected health information (in accordance&#xD;
             with national and local privacy regulations).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known active myocarditis, obstructive hypertrophic cardiomyopathy, congenital heart&#xD;
             disease, restrictive cardiomyopathy, constrictive pericarditis, uncorrected clinically&#xD;
             significant primary valvular disease.&#xD;
&#xD;
          2. Treatment with dobutamine at a dose &gt;5 μg/kg/min or use of drugs for support of BP at&#xD;
             the time of randomization.&#xD;
&#xD;
          3. Treatment with levosimendan, milrinone, or any other phosphodiesterase inhibitor&#xD;
             within 7 days before randomization.&#xD;
&#xD;
          4. Treatment with nesiritide within 30 days before randomization.&#xD;
&#xD;
          5. Creatinine clearance &lt;25 mL/min/1.73m² (as measured by the MDRD formula) at the time&#xD;
             of screening.&#xD;
&#xD;
          6. Planned coronary revascularization procedure (percutaneous coronary intervention or&#xD;
             coronary artery bypass grafting) within 5 days of randomization.&#xD;
&#xD;
          7. Clinical diagnosis of acute coronary syndrome meeting any 2 of the following 3&#xD;
             criteria:&#xD;
&#xD;
               1. Prolonged chest pain at rest, or an accelerated pattern of angina&#xD;
&#xD;
               2. Electrocardiogram changes indicative of ischemia or myocardial injury defined as:&#xD;
                  a new ST elevation at the J point of two anatomically contiguous leads with the&#xD;
                  cut-off points: ≥0.2 mV in men ≥40 years (&gt;0.25 mV in men &lt;40 years) or ≥0.15 mV&#xD;
                  in women in leads V2-V3 and/or ≥0.1 mV in other leads; or ST depression and T&#xD;
                  wave changes. New horizontal or down sloping ST depression ≥0.05 mV in two&#xD;
                  contiguous leads; and/or new T inversion ≥0.3 mV in two contiguous leads.&#xD;
&#xD;
               3. Serum troponin &gt;3 times upper limit of normal.&#xD;
&#xD;
          8. Clinically suspected acute mechanical cause of ADHF (e.g., papillary muscular&#xD;
             rupture). The diagnosis need not be confirmed by imaging or cardiac catheterization.&#xD;
&#xD;
          9. Anemia (hemoglobin &lt;9 g/dL or a hematocrit &lt;25%).&#xD;
&#xD;
         10. Known vasculitis, active infective endocarditis, or suspected infections, e.g.,&#xD;
             pneumonia, acute hepatitis, systemic inflammatory response syndrome, or sepsis.&#xD;
&#xD;
         11. Body temperature ≥38°C just prior to randomization.&#xD;
&#xD;
         12. Acute or chronic respiratory disorder (e.g., severe chronic obstructive pulmonary&#xD;
             disease) or primary pulmonary hypertension sufficient to cause dyspnea at rest, which&#xD;
             may interfere with the ability to interpret dyspnea assessments or hemodynamic&#xD;
             measurements.&#xD;
&#xD;
         13. Terminal illness other than congestive HF with expected survival &lt;180 days.&#xD;
&#xD;
         14. Any previous exposure to ularitide.&#xD;
&#xD;
         15. Known allergy to natriuretic peptides.&#xD;
&#xD;
         16. Participation in an investigational clinical drug study within 30 days prior to&#xD;
             randomization.&#xD;
&#xD;
         17. Current drug abuse or chronic alcoholism sufficient to impair participation and&#xD;
             compliance to the study protocol.&#xD;
&#xD;
         18. Women who are breast-feeding.&#xD;
&#xD;
         19. Women of child-bearing potential (i.e., pre-menopausal women) without documentation of&#xD;
             a negative urine/blood pregnancy assay within 12 h prior to randomization.&#xD;
&#xD;
         20. Any condition that, in the Investigator's opinion, makes the patient unsuitable for&#xD;
             study participation.&#xD;
&#xD;
         21. Legal incapacity or limited legal capacity.&#xD;
&#xD;
         22. Patients requiring mechanical circulatory support.&#xD;
&#xD;
         23. Patients with severe hepatic impairment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Milton Packer, MD</last_name>
    <role>Study Chair</role>
  </overall_official>
  <overall_official>
    <last_name>Christopher O'Connor, MD</last_name>
    <role>Principal Investigator</role>
  </overall_official>
  <overall_official>
    <last_name>William F. Peacock, MD</last_name>
    <role>Principal Investigator</role>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Huntsville</city>
        <state>Alabama</state>
        <zip>35801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Montgomery</city>
        <state>Alabama</state>
        <zip>36106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Littleton</city>
        <state>Colorado</state>
        <zip>80120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Trumbull</city>
        <state>Connecticut</state>
        <zip>06611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20422</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lawrenceville</city>
        <state>Georgia</state>
        <zip>30046</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Rockford</city>
        <state>Illinois</state>
        <zip>61107</zip>
        <country>United States</country>
      </address>
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  </location>
  <location>
    <facility>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Alexandria</city>
        <state>Louisiana</state>
        <zip>71303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Worcester</city>
        <state>Massachusetts</state>
        <zip>01655</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
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        <country>United States</country>
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  </location>
  <location>
    <facility>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48235</zip>
        <country>United States</country>
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    </facility>
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      <address>
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        <state>Michigan</state>
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      <address>
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        <state>Minnesota</state>
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        <country>United States</country>
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    <facility>
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        <state>Missouri</state>
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        <country>United States</country>
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      <address>
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        <state>Nebraska</state>
        <zip>68526</zip>
        <country>United States</country>
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    <facility>
      <address>
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        <state>New Jersey</state>
        <zip>07107</zip>
        <country>United States</country>
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    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
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        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
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  <location>
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      <address>
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        <state>Ohio</state>
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        <country>United States</country>
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      <address>
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        <country>United States</country>
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      <address>
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  <location>
    <facility>
      <address>
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        <state>Pennsylvania</state>
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  <location>
    <facility>
      <address>
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        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
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  <location>
    <facility>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37403</zip>
        <country>United States</country>
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  </location>
  <location>
    <facility>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
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  </location>
  <location>
    <facility>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78758</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
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  <location>
    <facility>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
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  </location>
  <location>
    <facility>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Midlothian</city>
        <state>Virginia</state>
        <zip>23114</zip>
        <country>United States</country>
      </address>
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  </location>
  <location>
    <facility>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23507</zip>
        <country>United States</country>
      </address>
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  <location>
    <facility>
      <address>
        <city>Salem</city>
        <state>Virginia</state>
        <zip>24153</zip>
        <country>United States</country>
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  <location>
    <facility>
      <address>
        <city>Ciudad Autonoma</city>
        <state>Buenos Aires</state>
        <zip>1180</zip>
        <country>Argentina</country>
      </address>
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  </location>
  <location>
    <facility>
      <address>
        <city>Coronel Suarez</city>
        <state>Buenos Aires</state>
        <zip>B7540GHD</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>La Plata</city>
        <state>Buenos Aires</state>
        <zip>1900</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Córdoba</city>
        <state>Cordoba</state>
        <zip>X5008KKF</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Vicente</city>
        <state>Cordoba</state>
        <zip>5006</zip>
        <country>Argentina</country>
      </address>
    </facility>
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  <location>
    <facility>
      <address>
        <city>Rosario</city>
        <state>Santa Fe</state>
        <zip>2000</zip>
        <country>Argentina</country>
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    </facility>
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  <location>
    <facility>
      <address>
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    <facility>
      <address>
        <city>Alicante</city>
        <zip>03010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Barcelona</city>
        <zip>08025</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Basel</city>
        <zip>4031</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lugano</city>
        <zip>6900</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Zuerich</city>
        <zip>8091</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Eskisehir</city>
        <zip>26480</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Istanbul</city>
        <zip>34662</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kocaeli</city>
        <zip>41300</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sivas</city>
        <zip>58140</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Belgium</country>
    <country>Brazil</country>
    <country>Canada</country>
    <country>Czechia</country>
    <country>Estonia</country>
    <country>Finland</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Latvia</country>
    <country>Lithuania</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Romania</country>
    <country>Serbia</country>
    <country>Spain</country>
    <country>Switzerland</country>
    <country>Turkey</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Chile</country>
    <country>Colombia</country>
    <country>Czech Republic</country>
  </removed_countries>
  <reference>
    <citation>Mitrovic V, Luss H, Nitsche K, Forssmann K, Maronde E, Fricke K, Forssmann WG, Meyer M. Effects of the renal natriuretic peptide urodilatin (ularitide) in patients with decompensated chronic heart failure: a double-blind, placebo-controlled, ascending-dose trial. Am Heart J. 2005 Dec;150(6):1239. doi: 10.1016/j.ahj.2005.01.022.</citation>
    <PMID>16338265</PMID>
  </reference>
  <reference>
    <citation>Mitrovic V, Seferovic PM, Simeunovic D, Ristic AD, Miric M, Moiseyev VS, Kobalava Z, Nitsche K, Forssmann WG, Luss H, Meyer M. Haemodynamic and clinical effects of ularitide in decompensated heart failure. Eur Heart J. 2006 Dec;27(23):2823-32. doi: 10.1093/eurheartj/ehl337. Epub 2006 Oct 30.</citation>
    <PMID>17074775</PMID>
  </reference>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>July 31, 2012</study_first_submitted>
  <study_first_submitted_qc>August 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 9, 2012</study_first_posted>
  <disposition_first_submitted>July 18, 2017</disposition_first_submitted>
  <disposition_first_submitted_qc>October 18, 2018</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">October 23, 2018</disposition_first_posted>
  <last_update_submitted>October 18, 2018</last_update_submitted>
  <last_update_submitted_qc>October 18, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Acute decompensated heart failure</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ularitide</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT01661634
org study id: ULA01
secondary id: 2010-024249-59
nct id: NCT01661634
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to evaluate the efficacy and safety of a continuous intravenous
      (IV) ularitide infusion on the clinical status and outcome of patients with acute
      decompensated heart failure (ADHF).
The objective of the TRUE-AHF study is to evaluate the effect of a 48-h continuous IV
      infusion of ularitide (15 ng/kg/min) versus placebo on the clinical status of patients with
      acute decompensated heart failure (ADHF).

      The study drug will be administered in addition to the standard treatment. The nature of
      standard therapy will be carried out according to the clinical judgment of the Investigator
      and may include vasodilator, inotropic, and diuretic drugs, as clinically indicated.

      There are two co-primary endpoints for this study. Co-primary endpoint 1 will be a
      hierarchical clinical composite variable that includes a patient-centered assessment of
      clinical progress, an assessment of lack of improvement or worsening of HF requiring a
      pre-specified intervention, and death.

      The endpoint is intended to mimic the assessment that would be carried out by a physician
      caring for the patient. If, during the 48 h infusion, a patient's clinical course
      deteriorates because he/she dies, fails to improve or develops worsening HF requiring a
      pre-specified intervention or if the patient considers his/her general clinical status as
      moderately or markedly worse, the patient will be considered to be "worse". If the patient
      considers his/her general clinical status as moderately or markedly improved and if such
      improvement is sustained without fulfilling the criteria for "worse" throughout the 48-h
      infusion (from 0 h to 48 h), the patient will be considered to be "improved". If the patient
      is neither improved nor worse, the patient's clinical status will be considered to be
      "unchanged".

      Co-primary efficacy endpoint 2 evaluates freedom from cardiovascular mortality during follow
      up after randomization, for the entire duration of the trial.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Two Co-primary Efficacy Endpoints
time frame: 6, 24, 48 hours post infusion through the entire duration of the trial
description: Improvement in a hierarchical clinical composite comprised of elements associated with: patient global assessment using a 7-point scale of symptomatic improvement, lack of improvement, or worsening; persistent or worsening heart failure (HF) requiring an intervention (initiation or intensification of IV therapy, circulatory or ventilatory mechanical support, surgical intervention, ultrafiltration, hemofiltration or dialysis); and all-cause mortality. Assessment of the clinical composite will be performed at 6 hour (h), 24 h and 48 h after start of IV ularitide infusion
Freedom from cardiovascular mortality during follow up after randomization, for the entire duration of the trial.
measure: Length of stay of index hospitalization in hours after start of study drug infusion
time frame: up to 30 days
measure: Length of stay in intensive care (intensive care unit [ICU] or critical care unit [CCU])
time frame: during the first 120 h following the start of the study drug infusion.
measure: Number of events of persistent or worsening HF requiring an intervention
time frame: from the start of the study drug infusion to 120 h.
measure: Proportion of patients with persistent or worsening HF and requiring an intervention
time frame: from the start of study drug infusion to 120 h.
measure: Reduction in rehospitalization for heart failure
time frame: within 30 days after initial hospital
measure: Changes of N-terminal pro brain natriuretic peptide (NT-pro BNP)
time frame: 48 h of treatment compared to baseline.
measure: Time to completion of last dose of any IV drugs that can be used for the treatment of HF (e.g., diuretics, vasodilators, or positive inotropic agents)
time frame: for the first 120 h following the start of the drug infusion.
measure: Change in serum creatinine
time frame: from baseline through 72 h.
measure: 180 days after start of study drug infusion, including patients still hospitalized at Day 30.
time frame: All-cause mortality and cardiovascular rehospitalization
arm group label: Ularitide
arm group type: Experimental
description: Ularitide, lyophilizate for i.v. infusion, 15 ng/kg BW/min, for 48 hours
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo lyophilizate for i.v. infusion
intervention type: Drug
intervention name: Ularitide
arm group label: Ularitide
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Milton Packer, MD
role: Study Chair
last name: Christopher O'Connor, MD
role: Principal Investigator
last name: William F. Peacock, MD
role: Principal Investigator
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country: Argentina
country: Belgium
country: Brazil
country: Canada
country: Czechia
country: Estonia
country: Finland
country: France
country: Germany
country: Hungary
country: Israel
country: Italy
country: Latvia
country: Lithuania
country: Netherlands
country: Poland
country: Romania
country: Serbia
country: Spain
country: Switzerland
country: Turkey
country: United States
country: Chile
country: Colombia
country: Czech Republic
citation: Mitrovic V, Luss H, Nitsche K, Forssmann K, Maronde E, Fricke K, Forssmann WG, Meyer M. Effects of the renal natriuretic peptide urodilatin (ularitide) in patients with decompensated chronic heart failure: a double-blind, placebo-controlled, ascending-dose trial. Am Heart J. 2005 Dec;150(6):1239. doi: 10.1016/j.ahj.2005.01.022.
PMID: 16338265
citation: Mitrovic V, Seferovic PM, Simeunovic D, Ristic AD, Miric M, Moiseyev VS, Kobalava Z, Nitsche K, Forssmann WG, Luss H, Meyer M. Haemodynamic and clinical effects of ularitide in decompensated heart failure. Eur Heart J. 2006 Dec;27(23):2823-32. doi: 10.1093/eurheartj/ehl337. Epub 2006 Oct 30.
PMID: 17074775
responsible party type: Sponsor
mesh term: Heart Failure
mesh term: Ularitide