<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/NCT01663662</url>
  </required_header>
  <id_info>
    <org_study_id>11-PAF06621</org_study_id>
    <nct_id>NCT01663662</nct_id>
  </id_info>
  <brief_title>The Use of Tolvaptan to Prevent Renal Dysfunction in High Risk Patients With Heart Failure-Pilot Study</brief_title>
  <official_title>The Use of Tolvaptan to Prevent Renal Dysfunction in High Risk Patients With Acute Decompensated Heart Failure-Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Otsuka Pharmaceuticals</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Michigan</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      It is well known that the use of loop diuretics in acute setting may decrease glomerular&#xD;
      filtration rate (GFR) and increase serum creatinine leading to renal dysfunction. Loop&#xD;
      diuretic induced elevation in serum creatinine can lead to increase in length of hospital&#xD;
      stay and possibly morbidity. Previous studies have suggested that tolvaptan unlike aggressive&#xD;
      loop diuretic therapy may not activate neurohormonal system nor decrease renal blood flow.&#xD;
      These properties may make tolvaptan a useful addition to diuretic therapy to prevent renal&#xD;
      dysfunction in high-risk patients. Therefore the primary objective of this study is to&#xD;
      determine if the use of tolvaptan in combination with diuretic therapy may prevent&#xD;
      development of renal dysfunction in high risk patients with heart failure.&#xD;
&#xD;
      Hypothesis: Administration of tolvaptan in combination with continuous loop diuretic therapy&#xD;
      in acutely decompensated heart failure patients at high risk for developing diuretic induced&#xD;
      renal dysfunction will have a lower proportion of patients increasing their serum creatinine&#xD;
      &gt; 0.3 mg/dL within a 96 hour time frame as compared to patients just receiving standard of&#xD;
      care continuous infusion diuretic.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Lack of eligible patients&#xD;
  </why_stopped>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">November 2013</completion_date>
  <primary_completion_date type="Actual">November 2013</primary_completion_date>
  <phase>Phase 4</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Renal dysfunction</measure>
    <time_frame>96 hours</time_frame>
    <description>Increase in serum creatinine &gt; 0.3 mg/dL within a 96 hours from enrollment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Weight</measure>
    <time_frame>24, 78, 72, 96</time_frame>
    <description>Change in weight over 24, 48, 72, and 96 hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urine output</measure>
    <time_frame>24, 48, 72, 96</time_frame>
    <description>Net urine output over 24, 48, 72, and 96 hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospitalization length of stay</measure>
    <time_frame>10</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Treatment Failure</measure>
    <time_frame>72hr</time_frame>
    <description>Need to increase diuretic dose in tolvaptan study group prior to 72 hr time point</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Heart Failure</condition>
  <arm_group>
    <arm_group_label>Tolvaptan Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Tolvaptan 30 mg qd x 3 days and Low Dose Loop Continuous Infusion - Initial Dosing:&#xD;
Furosemide - 10 mg/hr Bumentanide - 0.25 mg/hr Torsemide - 5 mg/hr</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo x 3 days and standard of care continuous infusion diuretic</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tolvaptan</intervention_name>
    <arm_group_label>Tolvaptan Arm</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;
          -  ≥ 18 years old&#xD;
&#xD;
          -  Prior clinical diagnosis of systolic heart failure (EF &lt; 40% within the past 18&#xD;
             months) with daily home use of oral loop diuretic for at least one month.&#xD;
&#xD;
          -  Daily oral dose of furosemide ≥ 40 mg and ≤ 240 mg (or equivalent)&#xD;
&#xD;
          -  Identified within 24 hours of hospital admission&#xD;
&#xD;
          -  Heart failure defined by at least 1 symptom (dyspnea, orthopnea, or edema) AND 1 sign&#xD;
             (rales on auscultation, peripheral edema, ascites, pulmonary vascular congestion on&#xD;
             chest radiography)&#xD;
&#xD;
          -  Anticipated need for IV loop diuretics for at least 48 hours&#xD;
&#xD;
          -  Likely requires daily net urine output in the range of 1-3 L/day for over a 72-96 hour&#xD;
             time period.&#xD;
&#xD;
          -  Albumin level &lt; 3.5 g/dL&#xD;
&#xD;
          -  Willingness to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Received or planned IV vasoactive treatment (inotropes, vasodilators) or&#xD;
             ultra-filtration therapy for heart failure&#xD;
&#xD;
          -  BNP &lt; 250 ng/ml or NT-proBNP &lt; 1000 mg/ml (if drawn for clinical purposes)&#xD;
&#xD;
          -  Systolic BP &lt; 90 mmHg&#xD;
&#xD;
          -  Serum creatinine &gt; 3.0 mg/dl at baseline or renal replacement therapy or creatinine&#xD;
             clearances &lt; 10 mL/min&#xD;
&#xD;
          -  Serum sodium &gt; 145 mEq/L&#xD;
&#xD;
          -  Acute coronary syndrome within 4 weeks&#xD;
&#xD;
          -  Anticipated need for coronary angiography or other procedures requiring IV contrast.&#xD;
&#xD;
          -  Patients receiving any of the following drugs: clarithromycin, ketoconazole,&#xD;
             itraconazole,ritonavir, indinavir, nelfinavir, saquinavir, nefazodone, telithromycin,&#xD;
             erythromycin, fluconazole, aprepitant, diltiazem, verapamil, cyclosporine, and&#xD;
             grapefruit juice.&#xD;
&#xD;
          -  Pregnant or nursing patients.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Barry E Bleske, Pharm. D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Michigan Health Systems</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2015</verification_date>
  <study_first_submitted>August 8, 2012</study_first_submitted>
  <study_first_submitted_qc>August 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2012</study_first_posted>
  <last_update_submitted>December 10, 2015</last_update_submitted>
  <last_update_submitted_qc>December 10, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 11, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>Barry E. Bleske</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Renal Insufficiency</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/NCT01663662
org study id: 11-PAF06621
nct id: NCT01663662
lead sponsor: 
collaborator: 
has dmc: No
It is well known that the use of loop diuretics in acute setting may decrease glomerular
      filtration rate (GFR) and increase serum creatinine leading to renal dysfunction. Loop
      diuretic induced elevation in serum creatinine can lead to increase in length of hospital
      stay and possibly morbidity. Previous studies have suggested that tolvaptan unlike aggressive
      loop diuretic therapy may not activate neurohormonal system nor decrease renal blood flow.
      These properties may make tolvaptan a useful addition to diuretic therapy to prevent renal
      dysfunction in high-risk patients. Therefore the primary objective of this study is to
      determine if the use of tolvaptan in combination with diuretic therapy may prevent
      development of renal dysfunction in high risk patients with heart failure.

      Hypothesis: Administration of tolvaptan in combination with continuous loop diuretic therapy
      in acutely decompensated heart failure patients at high risk for developing diuretic induced
      renal dysfunction will have a lower proportion of patients increasing their serum creatinine
      > 0.3 mg/dL within a 96 hour time frame as compared to patients just receiving standard of
      care continuous infusion diuretic.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Renal dysfunction
time frame: 96 hours
description: Increase in serum creatinine > 0.3 mg/dL within a 96 hours from enrollment
measure: Weight
time frame: 24, 78, 72, 96
description: Change in weight over 24, 48, 72, and 96 hours
measure: Urine output
time frame: 24, 48, 72, 96
description: Net urine output over 24, 48, 72, and 96 hours
measure: Hospitalization length of stay
time frame: 10
measure: Treatment Failure
time frame: 72hr
description: Need to increase diuretic dose in tolvaptan study group prior to 72 hr time point
arm group label: Tolvaptan Arm
arm group type: Active Comparator
description: Tolvaptan 30 mg qd x 3 days and Low Dose Loop Continuous Infusion - Initial Dosing:
Furosemide - 10 mg/hr Bumentanide - 0.25 mg/hr Torsemide - 5 mg/hr
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo x 3 days and standard of care continuous infusion diuretic
intervention type: Drug
intervention name: Tolvaptan
arm group label: Tolvaptan Arm
intervention type: Drug
intervention name: placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Barry E Bleske, Pharm. D.
role: Principal Investigator
affiliation: University of Michigan
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Michigan
investigator full name: Barry E. Bleske
investigator title: Associate Professor
mesh term: Renal Insufficiency
mesh term: Heart Failure
mesh term: Tolvaptan