xml: <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/NCT06036914</url>
    </required_header>
    <id_info>
      <org_study_id>23-005262</org_study_id>
      <nct_id>NCT06036914</nct_id>
    </id_info>
    <brief_title>A Study of Ultra High Dose Diuretics to Treat Heart Failure</brief_title>
    <official_title>Ultra High Dose Diuretic Strategy for Management of Acute Decompensated Heart Failure - A Randomized, Double-Blind Pilot Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Mayo Clinic</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Mayo Clinic</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this study is to determine the safety and effectiveness of ultrahigh dose&#xD;
        diuretics compared to standard dose diuretics over 24 hours in patients with decompensated&#xD;
        heart failure.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">January 2024</completion_date>
    <primary_completion_date type="Anticipated">January 2024</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>Urine Output</measure>
      <time_frame>24 hours</time_frame>
      <description>The total volume of urine produced in liters (L) over 24 hours after initiation of intravenous diuretic.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in Body Weight</measure>
      <time_frame>Baseline, 24 hours</time_frame>
      <description>Change in Body Weight (kg) from Baseline to 24 hours after initiation of intravenous diuretic.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in NT-proBNP</measure>
      <time_frame>Baseline, 24 hours</time_frame>
      <description>Change in NT-proBNP levels (pg/ml) from Baseline to 24 hours after initiation of intravenous diuretic.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Urine Sodium Excretion</measure>
      <time_frame>Baseline, 24 hours</time_frame>
      <description>Change in amount of sodium (mmol) excreted in the urine from Baseline to 24 hours after initiation of intravenous diuretic.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in apnea-hypopnea index</measure>
      <time_frame>Baseline, 24 hours</time_frame>
      <description>The apnea-hypopnea index (AHI) is the number of apneas and hypopneas per hour of sleep which is an indicator of severity of sleep apnea&#xD;
  AHI will be measured using a Watch Pat device at Baseline and 24 hours after initiation of intravenous diuretic.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Iothalamate glomerular filtration rate (GFR)</measure>
      <time_frame>Baseline, 24 hours</time_frame>
      <description>Renal or kidney function was measured by GFR determined by iothalamate clearance.&#xD;
  Iothalamate GFR will be measured at Baseline and 24 hours after initiation of intravenous diuretic.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Peripheral Vein Pressure</measure>
      <time_frame>Baseline, 24 hours</time_frame>
      <description>Peripheral vein pressure (mm Hg) will be recorded from existing IV lines through pressure transducer monitoring at Baseline and 24 hours after initiation of intravenous diuretic.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Cardiac Output</measure>
      <time_frame>Baseline, 24 hours</time_frame>
      <description>Cardiac output (L/min) is the total volume of blood moved by the heart per minute and will be measured by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in estimated Right Ventricular (RV) systolic pressure</measure>
      <time_frame>Baseline, 24 hours</time_frame>
      <description>Estimated RV systolic pressure (mm Hg) will be measured by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Right Atrial (RA) pressure</measure>
      <time_frame>Baseline, 24 hours</time_frame>
      <description>RA pressure (mm Hg) will be measured by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Left Atrial (LA) strain</measure>
      <time_frame>Baseline, 24 hours</time_frame>
      <description>LA strain will be assessed by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Left Ventricular (LV) global longitudinal strain</measure>
      <time_frame>Baseline, 24 hours</time_frame>
      <description>LV global longitudinal strain will be assessed by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Right Ventricular (RV) global longitudinal strain</measure>
      <time_frame>Baseline, 24 hours</time_frame>
      <description>RV global longitudinal strain will be assessed by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in E/e'</measure>
      <time_frame>Baseline, 24 hours</time_frame>
      <description>E/e' will be assessed using echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic. It is defined as the ratio of peak early diastolic mitral inflow velocity (E) and peak early diastolic mitral annular velocity (e').</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Heart Failure; With Decompensation</condition>
    <arm_group>
      <arm_group_label>Ultra-high dose diuretic group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subjects with decompensated heart failure requiring hospitalization will receive IV bumetanide.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Standard dose diuretic group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Subjects with decompensated heart failure requiring hospitalization will receive IV furosemide.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Bumetanide</intervention_name>
      <description>Bumetanide will be administered via intravenous (IV) infusion at a dose of 12.5 mg two times a day (BID) for 2 doses total within 24 hours.</description>
      <arm_group_label>Ultra-high dose diuretic group</arm_group_label>
      <other_name>Ultra-high dose diuretic</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Furosemide</intervention_name>
      <description>Furosemide will be administered via intravenous (IV) infusion at usual doses (twice the home dose of oral daily diuretic in furosemide equivalents) administered as 2 doses total within 24 hours.&#xD;
  Furosemide equivalents will be considered as follows (40 mg of intravenous furosemide = 1 mg oral bumetanide or 40 mg of torsemide or 80 mg of oral furosemide consistent with prior literature). The lowest dose of furosemide administered during the study will be 40 mg IV two times a day (BID) and the maximum dose will be 100 mg IV BID.</description>
      <arm_group_label>Standard dose diuretic group</arm_group_label>
      <other_name>Standard dose diuretic</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Diagnosis of decompensated heart failure receiving intravenous diuretics&#xD;
  &#xD;
            -  Ability to provide informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Patients on home inotrope medications&#xD;
  &#xD;
            -  Patients with Chronic Kidney disease stage V and end stage renal failure on dialysis&#xD;
  &#xD;
            -  Patients lacking the capacity to consent for themselves&#xD;
  &#xD;
            -  Known pregnancy or breastfeeding mothers&#xD;
  &#xD;
            -  Complex congenital heart disease&#xD;
  &#xD;
            -  Allergy to furosemide or bumetanide&#xD;
  &#xD;
            -  Respiratory failure requiring non-invasive ventilation (CPAP/BiPAP) or invasive&#xD;
               mechanical ventilatory support at the time of randomization&#xD;
  &#xD;
            -  Hypotension with systolic blood pressure &lt;80 mm Hg at the time of randomization&#xD;
  &#xD;
            -  Acute coronary syndrome&#xD;
  &#xD;
            -  Sustained Ventricular tachycardia requiring treatment in the last 48 hours&#xD;
  &#xD;
            -  Patients weighing ≤ 40 kg&#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>Yogesh Reddy, M.B.B.S</last_name>
      <role>Principal Investigator</role>
      <affiliation>Mayo Clinic</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Circulatory Failure Research Team</last_name>
      <phone>(507) 255-2200</phone>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Yogesh Reddy, M.B.B.S</last_name>
      <phone>(507) 284-3687</phone>
      <email>Reddy.Yogesh@mayo.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Mayo Clinic in Rochester</name>
        <address>
          <city>Rochester</city>
          <state>Minnesota</state>
          <zip>55905</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Circulatory Failure Research Team</last_name>
        <phone>507-255-2200</phone>
      </contact>
      <contact_backup>
        <last_name>Yogesh Reddy, M.B.B.S</last_name>
        <phone>(507) 284-3687</phone>
        <email>Reddy.Yogesh@mayo.edu</email>
      </contact_backup>
      <investigator>
        <last_name>Yogesh Reddy, MBBS</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Naveen Pereira, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>http://www.mayo.edu/research/clinical-trials</url>
      <description>Mayo Clinic Clinical Trials</description>
    </link>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 7, 2023</study_first_submitted>
    <study_first_submitted_qc>September 7, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 14, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Mayo Clinic</investigator_affiliation>
      <investigator_full_name>Yogesh Reddy</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <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>Furosemide</mesh_term>
      <mesh_term>Bumetanide</mesh_term>
      <mesh_term>Diuretics</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06036914
  org study id: 23-005262
  nct id: NCT06036914
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: No
  The purpose of this study is to determine the safety and effectiveness of ultrahigh dose
        diuretics compared to standard dose diuretics over 24 hours in patients with decompensated
        heart failure.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  measure: Urine Output
  time frame: 24 hours
  description: The total volume of urine produced in liters (L) over 24 hours after initiation of intravenous diuretic.
  measure: Change in Body Weight
  time frame: Baseline, 24 hours
  description: Change in Body Weight (kg) from Baseline to 24 hours after initiation of intravenous diuretic.
  measure: Change in NT-proBNP
  time frame: Baseline, 24 hours
  description: Change in NT-proBNP levels (pg/ml) from Baseline to 24 hours after initiation of intravenous diuretic.
  measure: Change in Urine Sodium Excretion
  time frame: Baseline, 24 hours
  description: Change in amount of sodium (mmol) excreted in the urine from Baseline to 24 hours after initiation of intravenous diuretic.
  measure: Change in apnea-hypopnea index
  time frame: Baseline, 24 hours
  description: The apnea-hypopnea index (AHI) is the number of apneas and hypopneas per hour of sleep which is an indicator of severity of sleep apnea
  AHI will be measured using a Watch Pat device at Baseline and 24 hours after initiation of intravenous diuretic.
  measure: Change in Iothalamate glomerular filtration rate (GFR)
  time frame: Baseline, 24 hours
  description: Renal or kidney function was measured by GFR determined by iothalamate clearance.
  Iothalamate GFR will be measured at Baseline and 24 hours after initiation of intravenous diuretic.
  measure: Change in Peripheral Vein Pressure
  time frame: Baseline, 24 hours
  description: Peripheral vein pressure (mm Hg) will be recorded from existing IV lines through pressure transducer monitoring at Baseline and 24 hours after initiation of intravenous diuretic.
  measure: Change in Cardiac Output
  time frame: Baseline, 24 hours
  description: Cardiac output (L/min) is the total volume of blood moved by the heart per minute and will be measured by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.
  measure: Change in estimated Right Ventricular (RV) systolic pressure
  time frame: Baseline, 24 hours
  description: Estimated RV systolic pressure (mm Hg) will be measured by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.
  measure: Change in Right Atrial (RA) pressure
  time frame: Baseline, 24 hours
  description: RA pressure (mm Hg) will be measured by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.
  measure: Change in Left Atrial (LA) strain
  time frame: Baseline, 24 hours
  description: LA strain will be assessed by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.
  measure: Change in Left Ventricular (LV) global longitudinal strain
  time frame: Baseline, 24 hours
  description: LV global longitudinal strain will be assessed by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.
  measure: Change in Right Ventricular (RV) global longitudinal strain
  time frame: Baseline, 24 hours
  description: RV global longitudinal strain will be assessed by echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic.
  measure: Change in E/e'
  time frame: Baseline, 24 hours
  description: E/e' will be assessed using echocardiography conducted at Baseline and 24 hours after initiation of intravenous diuretic. It is defined as the ratio of peak early diastolic mitral inflow velocity (E) and peak early diastolic mitral annular velocity (e').
  arm group label: Ultra-high dose diuretic group
  arm group type: Experimental
  description: Subjects with decompensated heart failure requiring hospitalization will receive IV bumetanide.
  arm group label: Standard dose diuretic group
  arm group type: Active Comparator
  description: Subjects with decompensated heart failure requiring hospitalization will receive IV furosemide.
  intervention type: Drug
  intervention name: Bumetanide
  description: Bumetanide will be administered via intravenous (IV) infusion at a dose of 12.5 mg two times a day (BID) for 2 doses total within 24 hours.
  arm group label: Ultra-high dose diuretic group
  other name: Ultra-high dose diuretic
  intervention type: Drug
  intervention name: Furosemide
  description: Furosemide will be administered via intravenous (IV) infusion at usual doses (twice the home dose of oral daily diuretic in furosemide equivalents) administered as 2 doses total within 24 hours.
  Furosemide equivalents will be considered as follows (40 mg of intravenous furosemide = 1 mg oral bumetanide or 40 mg of torsemide or 80 mg of oral furosemide consistent with prior literature). The lowest dose of furosemide administered during the study will be 40 mg IV two times a day (BID) and the maximum dose will be 100 mg IV BID.
  arm group label: Standard dose diuretic group
  other name: Standard dose diuretic
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Yogesh Reddy, M.B.B.S
  role: Principal Investigator
  affiliation: Mayo Clinic
  last name: Circulatory Failure Research Team
  phone: (507) 255-2200
  last name: Yogesh Reddy, M.B.B.S
  phone: (507) 284-3687
  email: Reddy.Yogesh@mayo.edu
  facility: 
  contact: 
  contact backup: 
  investigator: 
  investigator: 
  country: United States
  url: http://www.mayo.edu/research/clinical-trials
  description: Mayo Clinic Clinical Trials
  responsible party type: Principal Investigator
  investigator affiliation: Mayo Clinic
  investigator full name: Yogesh Reddy
  investigator title: Principal Investigator
  mesh term: Heart Failure
  mesh term: Furosemide
  mesh term: Bumetanide
  mesh term: Diuretics
  sharing ipd: No