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/NCT05986773</url>
    </required_header>
    <id_info>
      <org_study_id>P-Value-AHF</org_study_id>
      <nct_id>NCT05986773</nct_id>
    </id_info>
    <brief_title>Diuretic Strategies in Acute Heart Failure Patients at High Risk for Diuretic Resistance</brief_title>
    <acronym>P-Value-AHF</acronym>
    <official_title>Diuretic Strategies in Acute Heart Failure Patients at High Risk for Diuretic Resistance (P-Value-AHF): A Multicentre, Randomized, Parallel-group, Open-label Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Stadtspital Zürich</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Ospedale Regionale di Lugano</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Stadtspital Zürich</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The P-VALUE-AHF trial is a multicenter, randomized, open-label, parallel-group trial on the&#xD;
        diuretic and decongestive effects of different diuretic escalation strategies in patients&#xD;
        with acute heart failure and diuretic resistance.&#xD;
  &#xD;
        The main aims are&#xD;
  &#xD;
          -  to compare the diuretic efficacy of three therapeutic strategies in patients with acute&#xD;
             heart failure and diuretic resistance.&#xD;
  &#xD;
          -  to assess the improvement in clinical congestion and to compare the symptom-relief among&#xD;
             the different treatment regimens&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The P-VALUE-AHF trial is a multicenter, randomized, open-label, parallel-group trial on the&#xD;
        diuretic and decongestive effects of different diuretic escalation strategies in patients&#xD;
        with acute heart failure (AHF) and diuretic resistance (DR).&#xD;
  &#xD;
        Consenting patients with AHF and DR will be will be randomized towards 3 diuretic regimens.&#xD;
        Two to five hours after the initial standard dose Furosemide i.v,&#xD;
  &#xD;
          -  the first group will receive a doubled dose Furosemide (group FF)&#xD;
  &#xD;
          -  the second group will receive a combination of standard dose Furosemide and Metolazone&#xD;
             (group FM)&#xD;
  &#xD;
          -  the third group will receive a combination of standard dose Furosemide and Acetazolamide&#xD;
             (group FA)&#xD;
  &#xD;
        Objectives&#xD;
  &#xD;
          -  The primary objective is to compare the diuretic efficacy (measured as natriuresis and&#xD;
             urine volume) of three therapeutic strategies in patients with acute heart failure and&#xD;
             diuretic resistance.&#xD;
  &#xD;
          -  The secondary objective is to assess the improvement in clinical congestion (EVEREST&#xD;
             congestion score) and to compare the symptom-relief (improvement of dyspnoea (VAS))&#xD;
             among the different treatment regimens (FF vs. FM vs. FA).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2025</completion_date>
    <primary_completion_date type="Anticipated">August 1, 2025</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>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Diuretic efficacy after 6h</measure>
      <time_frame>6 hours after administration of the study-specific diuretic regimen</time_frame>
      <description>urine- natrium concentration (mmol/L)</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Diuretic efficacy after 2h</measure>
      <time_frame>2 hours after administration of the study-specific diuretic regimen</time_frame>
      <description>urine- natrium concentration (mmol/L)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Diuretic efficacy after 24h</measure>
      <time_frame>24 hours after administration of the study-specific diuretic regimen</time_frame>
      <description>urine- natrium concentration (mmol/L)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in clinical congestion</measure>
      <time_frame>0 and 24 hours after administration of the study-specific diuretic regimen</time_frame>
      <description>EVEREST congestion score</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in dyspnea severity</measure>
      <time_frame>0 and 24 hours after administration of the study-specific diuretic regimen.</time_frame>
      <description>numeric rating scale</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Safety Outcomes 1</measure>
      <time_frame>0-24 hours after administration of the study-specific diuretic regimen</time_frame>
      <description>Hypotension (SBP&lt; 90 mmHg) with symptoms or requiring therapeutic intervention</description>
    </other_outcome>
    <other_outcome>
      <measure>Safety Outcomes 2</measure>
      <time_frame>0-24 hours after administration of the study-specific diuretic regimen</time_frame>
      <description>Increase in serum creatinine &gt;50% from baseline</description>
    </other_outcome>
    <other_outcome>
      <measure>Safety Outcomes 3</measure>
      <time_frame>0-24 hours after administration of the study-specific diuretic regimen</time_frame>
      <description>New electrolyte disturbances (sodium &lt; 130mmol/l or &gt; 150mmol/l, potassium &lt; 3.0mmol/l or &gt; 5.5 mmol/l)</description>
    </other_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">75</enrollment>
    <condition>Acute Heart Failure</condition>
    <condition>Diuretic Resistance</condition>
    <arm_group>
      <arm_group_label>group FF</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Group FF will receive a doubled dose Furosemide i.v.&#xD;
  The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v.&#xD;
  Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>group FM</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Group FM will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o.&#xD;
  The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v.&#xD;
  Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection. Metolazone will be administered orally.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>group FA</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Group FA will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v.&#xD;
  The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v.&#xD;
  Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection. Acetazolamide (500mg) will be administered intravenously as a short infusion.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Furosemide</intervention_name>
      <description>Two to five hours after the initial standard dose Furosemide i.v, the patients are randomized towards 3 study-specific diuretic regimens: the first group will receive a doubled dose Furosemide i.v. (group FF), the second group will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o. (group FM), the third group will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v. (group FA).</description>
      <arm_group_label>group FA</arm_group_label>
      <arm_group_label>group FF</arm_group_label>
      <arm_group_label>group FM</arm_group_label>
      <other_name>Furosemide, doubled dose</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Metolazone</intervention_name>
      <description>Two to five hours after the initial standard dose Furosemide i.v, the patients are randomized towards 3 study-specific diuretic regimens: the first group will receive a doubled dose Furosemide i.v. (group FF), the second group will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o. (group FM), the third group will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v. (group FA).</description>
      <arm_group_label>group FM</arm_group_label>
      <other_name>Furosemide + Metolazone</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Acetazolamide</intervention_name>
      <description>Two to five hours after the initial standard dose Furosemide i.v, the patients are randomized towards 3 study-specific diuretic regimens: the first group will receive a doubled dose Furosemide i.v. (group FF), the second group will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o. (group FM), the third group will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v. (group FA).</description>
      <arm_group_label>group FA</arm_group_label>
      <other_name>Furosemide + Acetazolamide</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Elective or emergency hospital admission with clinical diagnosis of acute heart&#xD;
               failure&#xD;
  &#xD;
            -  One or more clinical signs of volume overload (i.e., peripheral edema, pleural&#xD;
               effusion, jugular venous distension)&#xD;
  &#xD;
            -  Low diuretic efficacy in the first 2 hours after the first standard dose Furosemide&#xD;
               i.v. (i.e., urine volume &lt; 300 ml and urine sodium concentration &lt; 70 mmol/L)&#xD;
  &#xD;
            -  Plasma N terminal-proBNP level at admission &gt; 1000 ng/L&#xD;
  &#xD;
            -  Signed Informed Consent form&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Previous use of intravenous diuretics during the index hospitalization (exception&#xD;
               first standard dose Furosemide i.v.)&#xD;
  &#xD;
            -  Maintenance treatment with Acetazolamide or Metolazone&#xD;
  &#xD;
            -  Use of any non-protocol defined diuretic agent that cannot be stopped upon study&#xD;
               inclusion except for sodium-glucose co-transporter-2 inhibitors (e.g., dapagliflozin,&#xD;
               empagliflozin, canagliflozin) and mineralocorticoid receptor antagonists (e.g.,&#xD;
               spironolactone, eplerenone)&#xD;
  &#xD;
            -  Systolic blood pressure &lt; 90 mmHg&#xD;
  &#xD;
            -  Expected use of intravenous vasopressors (e.g., noradrenaline, adrenaline), inotropes&#xD;
               (e.g., dobutamine, milrinone, levosimendan) at any time point during the study&#xD;
  &#xD;
            -  Severe chronic kidney disease (estimated glomerular filtration rate &lt; 15 ml/min/1.73&#xD;
               m2) or use of renal replacement therapy at any time before study inclusion&#xD;
  &#xD;
            -  Severe liver dysfunction or cirrhosis at risk of hepatic encephalopathy&#xD;
  &#xD;
            -  Severe electrolyte disturbances or metabolic acidosis requiring specific intravenous&#xD;
               treatment&#xD;
  &#xD;
            -  Concurrent diagnosis of acute coronary syndrome requiring urgent revascularization&#xD;
  &#xD;
            -  History of cardiac transplantation or ventricular assist device&#xD;
  &#xD;
            -  Allergy, intolerance or other contraindication against one of the study drugs&#xD;
  &#xD;
            -  Pregnancy or breastfeeding&#xD;
  &#xD;
            -  Age below 18 years.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>100 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Mattia Arrigo, PD, Dr. med.</last_name>
      <role>Principal Investigator</role>
      <affiliation>City Hospital Zürich Triemli, Birmensdorferstr. 497, 8063 Zürich, Switzerland</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Mattia Arrigo, PD, Dr. med.</last_name>
      <phone>+41 44 416 30 03</phone>
      <email>mattia.arrigo@stadtspital.ch</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Melina Stüssi-Helbling, Dr.med.</last_name>
      <phone>+41 44 416 31 13</phone>
      <email>melina.stuessi-helbling@stadtspital.ch</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>April 27, 2023</study_first_submitted>
    <study_first_submitted_qc>August 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 8, 2023</last_update_submitted>
    <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Diuretic therapy</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>Metolazone</mesh_term>
      <mesh_term>Furosemide</mesh_term>
      <mesh_term>Acetazolamide</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/NCT05986773
  org study id: P-Value-AHF
  nct id: NCT05986773
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The P-VALUE-AHF trial is a multicenter, randomized, open-label, parallel-group trial on the
        diuretic and decongestive effects of different diuretic escalation strategies in patients
        with acute heart failure and diuretic resistance.
  
        The main aims are
  
          -  to compare the diuretic efficacy of three therapeutic strategies in patients with acute
             heart failure and diuretic resistance.
  
          -  to assess the improvement in clinical congestion and to compare the symptom-relief among
             the different treatment regimens
  The P-VALUE-AHF trial is a multicenter, randomized, open-label, parallel-group trial on the
        diuretic and decongestive effects of different diuretic escalation strategies in patients
        with acute heart failure (AHF) and diuretic resistance (DR).
  
        Consenting patients with AHF and DR will be will be randomized towards 3 diuretic regimens.
        Two to five hours after the initial standard dose Furosemide i.v,
  
          -  the first group will receive a doubled dose Furosemide (group FF)
  
          -  the second group will receive a combination of standard dose Furosemide and Metolazone
             (group FM)
  
          -  the third group will receive a combination of standard dose Furosemide and Acetazolamide
             (group FA)
  
        Objectives
  
          -  The primary objective is to compare the diuretic efficacy (measured as natriuresis and
             urine volume) of three therapeutic strategies in patients with acute heart failure and
             diuretic resistance.
  
          -  The secondary objective is to assess the improvement in clinical congestion (EVEREST
             congestion score) and to compare the symptom-relief (improvement of dyspnoea (VAS))
             among the different treatment regimens (FF vs. FM vs. FA).
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Diuretic efficacy after 6h
  time frame: 6 hours after administration of the study-specific diuretic regimen
  description: urine- natrium concentration (mmol/L)
  measure: Diuretic efficacy after 2h
  time frame: 2 hours after administration of the study-specific diuretic regimen
  description: urine- natrium concentration (mmol/L)
  measure: Diuretic efficacy after 24h
  time frame: 24 hours after administration of the study-specific diuretic regimen
  description: urine- natrium concentration (mmol/L)
  measure: Change in clinical congestion
  time frame: 0 and 24 hours after administration of the study-specific diuretic regimen
  description: EVEREST congestion score
  measure: Change in dyspnea severity
  time frame: 0 and 24 hours after administration of the study-specific diuretic regimen.
  description: numeric rating scale
  measure: Safety Outcomes 1
  time frame: 0-24 hours after administration of the study-specific diuretic regimen
  description: Hypotension (SBP< 90 mmHg) with symptoms or requiring therapeutic intervention
  measure: Safety Outcomes 2
  time frame: 0-24 hours after administration of the study-specific diuretic regimen
  description: Increase in serum creatinine >50% from baseline
  measure: Safety Outcomes 3
  time frame: 0-24 hours after administration of the study-specific diuretic regimen
  description: New electrolyte disturbances (sodium < 130mmol/l or > 150mmol/l, potassium < 3.0mmol/l or > 5.5 mmol/l)
  arm group label: group FF
  arm group type: Active Comparator
  description: Group FF will receive a doubled dose Furosemide i.v.
  The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v.
  Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection.
  arm group label: group FM
  arm group type: Active Comparator
  description: Group FM will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o.
  The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v.
  Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection. Metolazone will be administered orally.
  arm group label: group FA
  arm group type: Active Comparator
  description: Group FA will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v.
  The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v.
  Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection. Acetazolamide (500mg) will be administered intravenously as a short infusion.
  intervention type: Drug
  intervention name: Furosemide
  description: Two to five hours after the initial standard dose Furosemide i.v, the patients are randomized towards 3 study-specific diuretic regimens: the first group will receive a doubled dose Furosemide i.v. (group FF), the second group will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o. (group FM), the third group will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v. (group FA).
  arm group label: group FA
  arm group label: group FF
  arm group label: group FM
  other name: Furosemide, doubled dose
  intervention type: Drug
  intervention name: Metolazone
  description: Two to five hours after the initial standard dose Furosemide i.v, the patients are randomized towards 3 study-specific diuretic regimens: the first group will receive a doubled dose Furosemide i.v. (group FF), the second group will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o. (group FM), the third group will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v. (group FA).
  arm group label: group FM
  other name: Furosemide + Metolazone
  intervention type: Drug
  intervention name: Acetazolamide
  description: Two to five hours after the initial standard dose Furosemide i.v, the patients are randomized towards 3 study-specific diuretic regimens: the first group will receive a doubled dose Furosemide i.v. (group FF), the second group will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o. (group FM), the third group will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v. (group FA).
  arm group label: group FA
  other name: Furosemide + Acetazolamide
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 100 Years
  healthy volunteers: No
  last name: Mattia Arrigo, PD, Dr. med.
  role: Principal Investigator
  affiliation: City Hospital Zürich Triemli, Birmensdorferstr. 497, 8063 Zürich, Switzerland
  last name: Mattia Arrigo, PD, Dr. med.
  phone: +41 44 416 30 03
  email: mattia.arrigo@stadtspital.ch
  last name: Melina Stüssi-Helbling, Dr.med.
  phone: +41 44 416 31 13
  email: melina.stuessi-helbling@stadtspital.ch
  responsible party type: Sponsor
  mesh term: Heart Failure
  mesh term: Metolazone
  mesh term: Furosemide
  mesh term: Acetazolamide
  sharing ipd: No