<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/NCT03259165</url>
  </required_header>
  <id_info>
    <org_study_id>17IRG33411129</org_study_id>
    <nct_id>NCT03259165</nct_id>
  </id_info>
  <brief_title>Nitroglycerin vs. Furosemide Using Lung Ultrasound Pilot Trial</brief_title>
  <acronym>N-FURIOUS</acronym>
  <official_title>Nitroglycerin vs. Furosemide Using Lung Ultrasound Pilot Trial (N-FURIOUS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Indiana University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Vanderbilt University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Indiana University</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>
      Nearly 80% of acute heart failure (AHF) patients admitted to the hospital are initially&#xD;
      treated in the emergency department (ED). Once admitted, within 30 days post-discharge, 27%&#xD;
      of patients are re-hospitalized or die. Attempts to improve outcomes with novel therapies&#xD;
      have all failed. The evidence for existing AHF therapies are poor: No currently used AHF&#xD;
      treatment is known to improve outcomes. ED treatment is largely the same today as 40 years&#xD;
      ago. Congestion, such as difficulty breathing, weight gain, and leg swelling, is the primary&#xD;
      reason why patients present to the hospital for AHF. Treating congestion is the cornerstone&#xD;
      of AHF management. Yet half of all AHF patients leave the hospital inadequately decongested.&#xD;
&#xD;
      Although it is the investigators' belief patients are often inadequately decongested in the&#xD;
      ED, it is common teaching within emergency medicine to focus on vasodilators and avoid or&#xD;
      minimize diuretics, especially in those patients with elevated blood pressure. This practice&#xD;
      is largely driven by retrospective analyses or small studies suggesting vasodilators are&#xD;
      efficacious and IV loop diuretics may be associated with harm. The evidence base to guide&#xD;
      early ED management is poor, and the AHA/ACC guidelines provide little to no guidance for ED&#xD;
      treatment. This reflects the lack of high quality data, a critical unmet need that the&#xD;
      investigators will address in this study.&#xD;
&#xD;
      Using clearance of LUS B-lines as the study endpoint, the investigators will study whether a&#xD;
      diuretic intense vs. nitrate intense strategy achieves better decongestion. Although nearly&#xD;
      two decades old, a small study of 100 patients suggested a nitrate intense strategy led to&#xD;
      better outcomes in AHF patients with pulmonary edema when compared with a diuretic intense&#xD;
      strategy. The investigators aim to perform a small pilot study, in hypertensive patients (SBP&#xD;
      &gt; 140mmHg) to test such a strategy to inform a larger, more definitive multicenter randomized&#xD;
      trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary goal of the N-FURIOUS pilot trial is to determine whether a nitrate intense&#xD;
      strategy safely reduces congestion, defined by LUS B-lines, better than a diuretic intense&#xD;
      strategy.&#xD;
&#xD;
      This pilot trial is designed to provide the necessary and sufficient information for a&#xD;
      larger, definitive trial.&#xD;
&#xD;
      PUBLIC HEALTH IMPACT:&#xD;
&#xD;
      Over one million hospitalizations for AHF occur every year in the US. Within 30 days after&#xD;
      hospitalization, over 25% of AHF patients will be dead or re-hospitalized. By one year after&#xD;
      hospitalization, up to 67% of patients will be re-hospitalized and 36% will be dead.&#xD;
      Worldwide, the costs of AHF exceed 100 billion annually. For patients aged 65 years and&#xD;
      older, AHF is the most common and most expensive reason for hospitalization. Despite major&#xD;
      reductions in morbidity and mortality for chronic HF, considerably less progress has been&#xD;
      seen in AHF.&#xD;
&#xD;
      The emergency department (ED) initiates diagnosis and management for the vast majority of AHF&#xD;
      patients. Nearly 80% of all admissions originate from the ED. Delays in diagnosis,&#xD;
      misdiagnosis, and delayed or improper treatment are costly, associated with greater morbidity&#xD;
      and mortality. Despite this crucial starting role, ED AHF pharmacological management today is&#xD;
      largely the same as 40 years ago. In fact, guidelines state: &quot;the treatment of AHF remains&#xD;
      largely opinion-based with little good evidence to guide therapy.&quot; Consensus statements from&#xD;
      the American Heart Association as well as a working group from the NHLBI on ED AHF management&#xD;
      further corroborate this lack of evidence: &quot;the evidence base on which this foundation of&#xD;
      acute care is built is astonishly thin.&quot; There remains a critical unmet need for evidence&#xD;
      based ED AHF management.&#xD;
&#xD;
      Limitations of Current AHF Therapy:&#xD;
&#xD;
      There are currently no Class I, Level of Evidence A therapeutic guideline recommendations for&#xD;
      AHF, highlighting the unmet need. In fact, therapeutic recommendations from the ACCF/AHA&#xD;
      begin with hospital based management, highlighting the absence of ED based evidence. The last&#xD;
      ED based guidelines were published in 2007 and have yet to be updated. The investigators&#xD;
      argue this lack of evidence leads to tremendous variation in ED care. Combined, this&#xD;
      contributes to worse outcomes.&#xD;
&#xD;
      Targeting Congestion in AHF:&#xD;
&#xD;
      Freedom from congestion is associated with improved outcomes; yet many patients leave the&#xD;
      hospital inadequately decongested. In fact, many patients leave the hospital without a&#xD;
      pre-discharge assessment of congestion. The investigators would argue, many ED AHF patients&#xD;
      are poorly assessed prior to hospitalization. The absence of robust, reliable methods to&#xD;
      assess congestion is a primary reason why it is not assessed. A recent consensus statement&#xD;
      published in 2010 highlights this fact: &quot;…no method to assess congestion prior to discharge&#xD;
      has been validated.&quot; While physical exam is currently the cornerstone of congestion&#xD;
      assessment, it lacks sensitivity and inter-rater reliability. The ED is the beginning of AHF&#xD;
      management for &gt;75% of admitted patients; delays in diagnosis, misdiagnosis, and resultant&#xD;
      delays in management are associated with greater morbidity and mortality.&#xD;
&#xD;
      Initial Therapy:&#xD;
&#xD;
      IV loop diuretics are the mainstay of AHF management. Yet emergency physicians are often&#xD;
      reluctant to use IV loop diuretics, largely influenced by small studies and retrospective&#xD;
      studies suggesting an association with harm. Nitrates are either recommended above diuretics&#xD;
      or even to replace diuretics in popular blogs, podcasts, or online forums. Arguably, neither&#xD;
      IV loop diuretics nor nitrates have definitive outcome data regarding efficacy or harm. This&#xD;
      is evident in guidelines, where IV loop diuretics receive a class I, B indication, and&#xD;
      nitrates a IIb, A recommendation. The evidence that does exist supports their use. Whether&#xD;
      one should be used before another, both, how to combine them, and in whom, is not well&#xD;
      defined.&#xD;
&#xD;
      Lung Ultrasound as an Endpoint:&#xD;
&#xD;
      For years, the lungs have been considered 'off-limits' to ultrasound: with aerated lungs, the&#xD;
      ultrasound beam is reflected and scattered due to acoustic mismatch. However, in the setting&#xD;
      of pulmonary congestion, extra vascular lung water (EVLW) can be directly visualized and&#xD;
      quantitated. Lung ultrasound measurement of B-lines are an objective, semi-quantitative&#xD;
      measure of extra vascular lung water (EVLW). B-lines are well-defined, vertical echogenic&#xD;
      lines, originating from water-thickened interlobular septa. They are a marker of congestion.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    COVID-19 pandemic. Initially had planned to resume study, but ultimately decided to close.&#xD;
  </why_stopped>
  <start_date type="Actual">December 14, 2017</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2021</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The total number of B-lines at the conclusion of ED AHF management</measure>
    <time_frame>During the ED phase of management, no more than 6 hours</time_frame>
    <description>The total number of B-lines at the conclusion of ED AHF management or maximum of 6 hours after enrollment, whichever comes first.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Dyspnea assessment</measure>
    <time_frame>During the ED phase of management, no more than 6 hours</time_frame>
    <description>A patient reported measurement of dyspnea using both 5 and 7-point Likert scales in a standardized position</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>B-lines &lt;= 15 at the conclusion of ED AHF management</measure>
    <time_frame>During the ED phase of management, no more than 6 hours</time_frame>
    <description>B-lines &lt;= 15 at the conclusion of ED AHF management or maximum of 6 hours after enrollment, whichever comes first</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Total DAOOH</measure>
    <time_frame>Up through 30 days post discharge</time_frame>
    <description>Total days alive and out of hospital through 30 days post-discharge</description>
  </other_outcome>
  <other_outcome>
    <measure>Association of B-lines at discharge and 30-day outcome</measure>
    <time_frame>Up through 30 days post discharge</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Time to reach B-lines &lt;15</measure>
    <time_frame>Throughout hospitalization, on average 5-7 days</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Association of baseline, discharge, and change of b-lines with 30-day outcomes</measure>
    <time_frame>Up through 30 days post discharge</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>All Cause readmissions, All cause ED re-visits</measure>
    <time_frame>30 days post discharge</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in physical exam findings and body weight from presentation to pre-discharge</measure>
    <time_frame>From admission to pre-discharge from the hospital, on average 5 to 7 days</time_frame>
    <description>Physical exam includes peripheral edema, jugular venous distention, pulmonary and cardiac auscultation</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">51</enrollment>
  <condition>Heart Failure</condition>
  <condition>Heart Failure Acute</condition>
  <condition>Acute Cardiac Failure</condition>
  <condition>Acute Cardiac Pulmonary Edema</condition>
  <arm_group>
    <arm_group_label>Nitrate Intense Strategy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients randomized to the Nitrate intense strategy will be treated according to protocol with nitrates in combination with IV loop diuretics. This protocol only involves therapies used in everyday AHF clinical practice.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diuretic Intense Strategy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients randomized to the Diuretic intense strategy will be treated according to protocol with IV loop diuretics in combination with nitrates. This protocol only involves therapies used in everyday AHF clinical practice.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nitrates</intervention_name>
    <description>For patients randomized to the Nitrate intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.&#xD;
Treatment protocol:&#xD;
IV furosemide (unless already given) (All patients receive at minimum 20 mg IV furosemide or equivalent)&#xD;
SL nitroglycerin (400 ucg) will be given every 5 minutes, a total of three times. (May be repeated) (Held if SBP decreases to &lt; 120 mmHg)&#xD;
Reassessment every 2 hours. If LUS B-lines &gt;15, repeat step 2. If &lt; 15, stop algorithm.</description>
    <arm_group_label>Nitrate Intense Strategy</arm_group_label>
    <other_name>SL or IV Nitrates</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Loop Diuretics</intervention_name>
    <description>For patients randomized to the Diuretic intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.&#xD;
Treatment protocol:&#xD;
Patients receive 1 inch topical nitropaste&#xD;
IV Loop diuretic dose = patients total oral dose (max dose of 200 mg IV)&#xD;
Reassessment every 2 hours. If LUS B-lines &gt;15, repeat step 2. If &lt; 15, stop algorithm.</description>
    <arm_group_label>Diuretic Intense Strategy</arm_group_label>
    <other_name>IV Loop Diuretics</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 21 years&#xD;
&#xD;
          -  Presents with shortness of breath at rest or with minimal exertion&#xD;
&#xD;
          -  Clinical diagnosis of AHF and presence of &gt; 15 total bilateral B-lines distributed in&#xD;
             at least 4 zones on initial LUS&#xD;
&#xD;
          -  Hx of chronic HF and ANY ONE OF THE FOLLOWING:&#xD;
&#xD;
          -  [Chest radiograph consistent with AHF&#xD;
&#xD;
          -  Jugular venous distension&#xD;
&#xD;
          -  Pulmonary rales on auscultation&#xD;
&#xD;
          -  Lower extremity edema&#xD;
&#xD;
          -  BNP &gt; 500pg/mL]&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronic renal dysfunction, including ESRD or eGFR &lt; 20 ml//min/1.73m2.&#xD;
&#xD;
          -  Shock of any kind. Any requirement for vasopressors or inotropes.&#xD;
&#xD;
          -  SBP &lt; 120&#xD;
&#xD;
          -  Need for immediate intubation&#xD;
&#xD;
          -  Acute Coronary Syndrome OR new ST-segment elevation/depression on EKG. (troponin&#xD;
             release outside of ACS is allowed)&#xD;
&#xD;
          -  Fever &gt;101.5ºF&#xD;
&#xD;
          -  End stage HF: transplant list, ventricular assist device&#xD;
&#xD;
          -  Anemia requiring transfusion&#xD;
&#xD;
          -  Known interstitial lung disease&#xD;
&#xD;
          -  Suspected acute lung injury or acute respiratory distress syndrome (ARDS)&#xD;
&#xD;
          -  Pregnant or recently pregnant within the last 6 months&#xD;
&#xD;
          -  Severe valvular disease&#xD;
&#xD;
          -  Anuria&#xD;
&#xD;
          -  Allergy or hypersensitivity to nitroglycerin, furosemide or sulfa&#xD;
&#xD;
          -  Concern for cardiac tamponade or restrictive cardiomyopathy&#xD;
&#xD;
          -  Elevated intracranial pressure&#xD;
&#xD;
          -  Recent use of PDE5 inhibitors&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peter S Pang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Indiana University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Eskenazi Health</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IU Health Methodist Hospital</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>August 19, 2017</study_first_submitted>
  <study_first_submitted_qc>August 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <last_update_submitted>March 24, 2022</last_update_submitted>
  <last_update_submitted_qc>March 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Indiana University</investigator_affiliation>
    <investigator_full_name>PETER S PANG</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Heart Failure</keyword>
  <keyword>Acute Heart Failure</keyword>
  <keyword>Pulmonary Edema</keyword>
  <keyword>Lung Ultrasound</keyword>
  <keyword>Extra vascular lung water</keyword>
  <keyword>B-lines</keyword>
  <keyword>Diuretics</keyword>
  <keyword>Nitrates</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Edema</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>Diuretics</mesh_term>
    <mesh_term>Sodium Potassium Chloride Symporter Inhibitors</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>September 4, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03259165
org study id: 17IRG33411129
nct id: NCT03259165
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Nearly 80% of acute heart failure (AHF) patients admitted to the hospital are initially
      treated in the emergency department (ED). Once admitted, within 30 days post-discharge, 27%
      of patients are re-hospitalized or die. Attempts to improve outcomes with novel therapies
      have all failed. The evidence for existing AHF therapies are poor: No currently used AHF
      treatment is known to improve outcomes. ED treatment is largely the same today as 40 years
      ago. Congestion, such as difficulty breathing, weight gain, and leg swelling, is the primary
      reason why patients present to the hospital for AHF. Treating congestion is the cornerstone
      of AHF management. Yet half of all AHF patients leave the hospital inadequately decongested.

      Although it is the investigators' belief patients are often inadequately decongested in the
      ED, it is common teaching within emergency medicine to focus on vasodilators and avoid or
      minimize diuretics, especially in those patients with elevated blood pressure. This practice
      is largely driven by retrospective analyses or small studies suggesting vasodilators are
      efficacious and IV loop diuretics may be associated with harm. The evidence base to guide
      early ED management is poor, and the AHA/ACC guidelines provide little to no guidance for ED
      treatment. This reflects the lack of high quality data, a critical unmet need that the
      investigators will address in this study.

      Using clearance of LUS B-lines as the study endpoint, the investigators will study whether a
      diuretic intense vs. nitrate intense strategy achieves better decongestion. Although nearly
      two decades old, a small study of 100 patients suggested a nitrate intense strategy led to
      better outcomes in AHF patients with pulmonary edema when compared with a diuretic intense
      strategy. The investigators aim to perform a small pilot study, in hypertensive patients (SBP
      > 140mmHg) to test such a strategy to inform a larger, more definitive multicenter randomized
      trial.
The primary goal of the N-FURIOUS pilot trial is to determine whether a nitrate intense
      strategy safely reduces congestion, defined by LUS B-lines, better than a diuretic intense
      strategy.

      This pilot trial is designed to provide the necessary and sufficient information for a
      larger, definitive trial.

      PUBLIC HEALTH IMPACT:

      Over one million hospitalizations for AHF occur every year in the US. Within 30 days after
      hospitalization, over 25% of AHF patients will be dead or re-hospitalized. By one year after
      hospitalization, up to 67% of patients will be re-hospitalized and 36% will be dead.
      Worldwide, the costs of AHF exceed 100 billion annually. For patients aged 65 years and
      older, AHF is the most common and most expensive reason for hospitalization. Despite major
      reductions in morbidity and mortality for chronic HF, considerably less progress has been
      seen in AHF.

      The emergency department (ED) initiates diagnosis and management for the vast majority of AHF
      patients. Nearly 80% of all admissions originate from the ED. Delays in diagnosis,
      misdiagnosis, and delayed or improper treatment are costly, associated with greater morbidity
      and mortality. Despite this crucial starting role, ED AHF pharmacological management today is
      largely the same as 40 years ago. In fact, guidelines state: "the treatment of AHF remains
      largely opinion-based with little good evidence to guide therapy." Consensus statements from
      the American Heart Association as well as a working group from the NHLBI on ED AHF management
      further corroborate this lack of evidence: "the evidence base on which this foundation of
      acute care is built is astonishly thin." There remains a critical unmet need for evidence
      based ED AHF management.

      Limitations of Current AHF Therapy:

      There are currently no Class I, Level of Evidence A therapeutic guideline recommendations for
      AHF, highlighting the unmet need. In fact, therapeutic recommendations from the ACCF/AHA
      begin with hospital based management, highlighting the absence of ED based evidence. The last
      ED based guidelines were published in 2007 and have yet to be updated. The investigators
      argue this lack of evidence leads to tremendous variation in ED care. Combined, this
      contributes to worse outcomes.

      Targeting Congestion in AHF:

      Freedom from congestion is associated with improved outcomes; yet many patients leave the
      hospital inadequately decongested. In fact, many patients leave the hospital without a
      pre-discharge assessment of congestion. The investigators would argue, many ED AHF patients
      are poorly assessed prior to hospitalization. The absence of robust, reliable methods to
      assess congestion is a primary reason why it is not assessed. A recent consensus statement
      published in 2010 highlights this fact: "…no method to assess congestion prior to discharge
      has been validated." While physical exam is currently the cornerstone of congestion
      assessment, it lacks sensitivity and inter-rater reliability. The ED is the beginning of AHF
      management for >75% of admitted patients; delays in diagnosis, misdiagnosis, and resultant
      delays in management are associated with greater morbidity and mortality.

      Initial Therapy:

      IV loop diuretics are the mainstay of AHF management. Yet emergency physicians are often
      reluctant to use IV loop diuretics, largely influenced by small studies and retrospective
      studies suggesting an association with harm. Nitrates are either recommended above diuretics
      or even to replace diuretics in popular blogs, podcasts, or online forums. Arguably, neither
      IV loop diuretics nor nitrates have definitive outcome data regarding efficacy or harm. This
      is evident in guidelines, where IV loop diuretics receive a class I, B indication, and
      nitrates a IIb, A recommendation. The evidence that does exist supports their use. Whether
      one should be used before another, both, how to combine them, and in whom, is not well
      defined.

      Lung Ultrasound as an Endpoint:

      For years, the lungs have been considered 'off-limits' to ultrasound: with aerated lungs, the
      ultrasound beam is reflected and scattered due to acoustic mismatch. However, in the setting
      of pulmonary congestion, extra vascular lung water (EVLW) can be directly visualized and
      quantitated. Lung ultrasound measurement of B-lines are an objective, semi-quantitative
      measure of extra vascular lung water (EVLW). B-lines are well-defined, vertical echogenic
      lines, originating from water-thickened interlobular septa. They are a marker of congestion.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The total number of B-lines at the conclusion of ED AHF management
time frame: During the ED phase of management, no more than 6 hours
description: The total number of B-lines at the conclusion of ED AHF management or maximum of 6 hours after enrollment, whichever comes first.
measure: Dyspnea assessment
time frame: During the ED phase of management, no more than 6 hours
description: A patient reported measurement of dyspnea using both 5 and 7-point Likert scales in a standardized position
measure: B-lines <= 15 at the conclusion of ED AHF management
time frame: During the ED phase of management, no more than 6 hours
description: B-lines <= 15 at the conclusion of ED AHF management or maximum of 6 hours after enrollment, whichever comes first
measure: Total DAOOH
time frame: Up through 30 days post discharge
description: Total days alive and out of hospital through 30 days post-discharge
measure: Association of B-lines at discharge and 30-day outcome
time frame: Up through 30 days post discharge
measure: Time to reach B-lines <15
time frame: Throughout hospitalization, on average 5-7 days
measure: Association of baseline, discharge, and change of b-lines with 30-day outcomes
time frame: Up through 30 days post discharge
measure: All Cause readmissions, All cause ED re-visits
time frame: 30 days post discharge
measure: Change in physical exam findings and body weight from presentation to pre-discharge
time frame: From admission to pre-discharge from the hospital, on average 5 to 7 days
description: Physical exam includes peripheral edema, jugular venous distention, pulmonary and cardiac auscultation
arm group label: Nitrate Intense Strategy
arm group type: Experimental
description: Patients randomized to the Nitrate intense strategy will be treated according to protocol with nitrates in combination with IV loop diuretics. This protocol only involves therapies used in everyday AHF clinical practice.
arm group label: Diuretic Intense Strategy
arm group type: Experimental
description: Patients randomized to the Diuretic intense strategy will be treated according to protocol with IV loop diuretics in combination with nitrates. This protocol only involves therapies used in everyday AHF clinical practice.
intervention type: Drug
intervention name: Nitrates
description: For patients randomized to the Nitrate intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.
Treatment protocol:
IV furosemide (unless already given) (All patients receive at minimum 20 mg IV furosemide or equivalent)
SL nitroglycerin (400 ucg) will be given every 5 minutes, a total of three times. (May be repeated) (Held if SBP decreases to < 120 mmHg)
Reassessment every 2 hours. If LUS B-lines >15, repeat step 2. If < 15, stop algorithm.
arm group label: Nitrate Intense Strategy
other name: SL or IV Nitrates
intervention type: Drug
intervention name: Loop Diuretics
description: For patients randomized to the Diuretic intense arm, the treatment protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first.
Treatment protocol:
Patients receive 1 inch topical nitropaste
IV Loop diuretic dose = patients total oral dose (max dose of 200 mg IV)
Reassessment every 2 hours. If LUS B-lines >15, repeat step 2. If < 15, stop algorithm.
arm group label: Diuretic Intense Strategy
other name: IV Loop Diuretics
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Peter S Pang, MD
role: Principal Investigator
affiliation: Indiana University
facility: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Indiana University
investigator full name: PETER S PANG
investigator title: Associate Professor
mesh term: Pulmonary Edema
mesh term: Heart Failure
mesh term: Diuretics
mesh term: Sodium Potassium Chloride Symporter Inhibitors
sharing ipd: No
submitted: September 4, 2023