<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/NCT03002467</url>
  </required_header>
  <id_info>
    <org_study_id>iAPP study</org_study_id>
    <nct_id>NCT03002467</nct_id>
  </id_info>
  <brief_title>Impact Analysis of Prognostic Stratification for Pulmonary Embolism</brief_title>
  <acronym>iAPP</acronym>
  <official_title>Impact Analysis of Prognostic Stratification for Pulmonary Embolism: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Università degli Studi dell'Insubria</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Università degli Studi dell'Insubria</source>
  <brief_summary>
    <textblock>
      The Investigator postulate that the use of PESI in addition to routine clinical practice, as&#xD;
      opposed to routine clinical practice based on clinical judgment alone, will help physicians&#xD;
      to correctly identify PE patients at low-risk of adverse outcomes. Considered that low-risk&#xD;
      patients could benefit from a short hospital stay, aim of this study is to demonstrate that&#xD;
      the use of PESI will lead physicians to discharge these patients earlier, thus reducing the&#xD;
      duration of hospital stay of PE patients (primary outcome).&#xD;
&#xD;
      Outpatients diagnosed with PE at the emergency department (ED) and admitted to participating&#xD;
      units represent the target population&#xD;
&#xD;
      As the availability of DOACs may influence the duration of hospital stay, the secondary&#xD;
      objectives of the present study are:&#xD;
&#xD;
        1. to demonstrate that a shorter hospital stay for low-risk PE patients (independently on&#xD;
           the method used to identify them) will reduce the incidence of hospital-associated&#xD;
           complications and improve patients satisfaction and quality of life, without increasing&#xD;
           the incidence of PE-related complications&#xD;
&#xD;
        2. to demonstrate that the use of PESI, as opposed to clinical judgment alone, will be&#xD;
           associated with a greater proportion of patients discharged early (&lt; 72 hours from ED&#xD;
           admission) or treated entirely at home (&lt; 24 hours from ED admission).&#xD;
&#xD;
        3. to demonstrate that the use of DOACs will reduce the duration of hospital stay of PE&#xD;
           patients&#xD;
&#xD;
        4. to demonstrate that the use of DOACs, as opposed to standard treatment, will be&#xD;
           associated with a greater proportion of patients discharged early (&lt; 72 hours from ED&#xD;
           admission) or treated entirely at home (&lt; 24 hours from ED admission).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      STUDY DESIGN&#xD;
&#xD;
      Within 24 hours from acute PE diagnosis, each treating physician (local Investigator) will be&#xD;
      centrally randomized. Treating physicians (local Investigator) of the participating Units&#xD;
      will call the coordinating centres by phone for randomization. Before randomization, in order&#xD;
      to avoid any influence on treatment choice, each treating physician (local Investigator)&#xD;
      should declare in advance which treatment strategy will use for his patient&#xD;
      (intention-to-treat), i.e. standard treatment with heparin plus vitamin K antagonist&#xD;
      (standard group) or DOACs (DOACs group) Randomization will be stratified by treatment choice&#xD;
      of the local Investigator. Each of two 'intention-to-treat' approaches will be therefore&#xD;
      randomized to two arms, i.e. arm 1 or arm 2.&#xD;
&#xD;
      Arm 1: treating physicians must formally calculate PESI and report in the clinical record&#xD;
      form* each day of hospitalization on top of routine clinical practice (standard care)&#xD;
&#xD;
      Arm 2: standard care (i.e. no formally calculation of PESI on top)&#xD;
&#xD;
      Randomization will be performed centrally with a 1:1 ratio, following a computer-generated&#xD;
      list of randomization.&#xD;
&#xD;
      STUDY POPULATION&#xD;
&#xD;
      1.1 Population&#xD;
&#xD;
      Randomised physicians:&#xD;
&#xD;
      Each Local Investigator of participating canters. All participating centres are Internal&#xD;
      Medicine Unit.&#xD;
&#xD;
      PE population:&#xD;
&#xD;
      Consecutive adult outpatients of any age, gender and race, with an objectively confirmed&#xD;
      diagnosis of a suspected or unsuspected acute PE at the emergency department (ED) and&#xD;
      admitted to participating units will be included.&#xD;
&#xD;
      Suspected PE means that diagnosis has been made by an imaging test (computed tomographic&#xD;
      pulmonary angiography [CTPA], pulmonary angiography, V/Q lung scan) prescribed by a treating&#xD;
      physician who had clinical suspicion of PE.&#xD;
&#xD;
      Unsuspected PE means that diagnosis has been made incidentally by an imaging test performed&#xD;
      for other clinical indications (e.g. cancer staging or follow-up).&#xD;
&#xD;
      Objective diagnosis of acute PE means: a positive computed tomographic pulmonary angiography&#xD;
      (CTPA), a positive pulmonary angiography, a high-probability V/Q lung scan (or perfusion lung&#xD;
      scan with negative chest X-ray), or intermediate probability V/Q or perfusion lung scan with&#xD;
      proximal deep-vein thrombosis (DVT) documented by compression ultrasonography.&#xD;
&#xD;
      1.2 Sample size calculation&#xD;
&#xD;
      The Investigators hypothesize that the distribution of hospital stay duration for PE will&#xD;
      have a standard deviation of 4 days. The I vestigators also hypothesize that the mean&#xD;
      duration of hospital stay will be reduced by at least 15% in PE patients whose treating&#xD;
      physician will be randomised to formally use PESI and by 5% in PE patients whose treating&#xD;
      physician will not be randomised to formally calculate PESI. Low-risk PE patients are almost&#xD;
      50% of all PE population. Therefore, with an α error of 0.05 and a statistical power (1-β&#xD;
      error) of 80%, 200 patients for each group (a total of 400 patients) need to be enrolled to&#xD;
      find a statistically significant difference (p&lt;0.05) between the mean hospital stay length.&#xD;
      As the variable 'hospital stay length' will have a non-normal distribution and needs to be&#xD;
      expressed and reported as median, 10% extra patients need to be enrolled to reach a&#xD;
      statistically significant difference with the previous statistical assumptions.&#xD;
&#xD;
      Final total sample size will be, therefore, of 440 patients (220 patients for each group)&#xD;
&#xD;
      OUTCOMES&#xD;
&#xD;
        1. Main study parameter/endpoint&#xD;
&#xD;
           The primary outcome is the median length of hospital stay&#xD;
&#xD;
        2. Secondary study parameters/endpoints&#xD;
&#xD;
      The secondary efficacy outcomes will be the following:&#xD;
&#xD;
        1. health-system measures&#xD;
&#xD;
             -  proportion of patients undergoing short-hospital stay&#xD;
&#xD;
             -  proportion of patients undergoing complete home-treatment&#xD;
&#xD;
             -  post-discharge hospital re-admission&#xD;
&#xD;
             -  post-discharge outpatient visits to emergency department&#xD;
&#xD;
        2. patient-related outcomes&#xD;
&#xD;
             -  quality of life (5-point Likert scale questionnaire)&#xD;
&#xD;
      The safety outcomes will be the following:&#xD;
&#xD;
        1. overall mortality&#xD;
&#xD;
        2. PE-related&#xD;
&#xD;
             -  PE-related mortality&#xD;
&#xD;
             -  recurrent PE and/or deep vein thrombosis (DVT)&#xD;
&#xD;
             -  major bleeding&#xD;
&#xD;
             -  clinically relevant non-major bleeding&#xD;
&#xD;
             -  minor bleeding&#xD;
&#xD;
             -  other anticoagulation-related complications (hematoma/infection at heparin or&#xD;
                fondaparinux injection sites, heparin-induced thrombocytopenia)&#xD;
&#xD;
        3. Hospitalization-related&#xD;
&#xD;
             -  hospital-acquired infections (pneumonia; urinary tract infection; other)&#xD;
&#xD;
             -  iatrogenic complications&#xD;
&#xD;
             -  immobilization syndrome&#xD;
&#xD;
             -  pressure sores&#xD;
&#xD;
      Overall mortality, PE-related safety outcomes, post-discharge hospital re-admission and&#xD;
      outpatient visits to emergency department will be measured at 14 days, 30 days, and 90 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low recruitment rate&#xD;
  </why_stopped>
  <start_date>September 2016</start_date>
  <completion_date type="Actual">December 2019</completion_date>
  <primary_completion_date type="Actual">December 2019</primary_completion_date>
  <phase>N/A</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Length of hospital stay</measure>
    <time_frame>Up to 3 months</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">125</enrollment>
  <condition>Pulmonary Embolism</condition>
  <arm_group>
    <arm_group_label>PESI score</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>treating physicians must formally calculate PESI and report in the clinical record form* each day of hospitalization on top of routine clinical practice (standard care)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>standard care (i.e. no formally calculation of PESI on top)</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>PESI score</intervention_name>
    <arm_group_label>PESI score</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Outpatients with objectively diagnosed PE, both suspected or unsuspected (e.g. during&#xD;
             CT for cancer staging and/or follow-up)&#xD;
&#xD;
          -  Age &gt; 18 years&#xD;
&#xD;
          -  Signature of written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Children&#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>Alessandro Squizzato, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Università degli Studi dell'Insubria</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Cuneo</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>December 11, 2016</study_first_submitted>
  <study_first_submitted_qc>December 20, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 23, 2016</study_first_posted>
  <last_update_submitted>November 13, 2020</last_update_submitted>
  <last_update_submitted_qc>November 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Università degli Studi dell'Insubria</investigator_affiliation>
    <investigator_full_name>Alessandro Squizzato</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>Pulmonary Embolism</mesh_term>
    <mesh_term>Embolism</mesh_term>
  </condition_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/NCT03002467
org study id: iAPP study
nct id: NCT03002467
lead sponsor: 
The Investigator postulate that the use of PESI in addition to routine clinical practice, as
      opposed to routine clinical practice based on clinical judgment alone, will help physicians
      to correctly identify PE patients at low-risk of adverse outcomes. Considered that low-risk
      patients could benefit from a short hospital stay, aim of this study is to demonstrate that
      the use of PESI will lead physicians to discharge these patients earlier, thus reducing the
      duration of hospital stay of PE patients (primary outcome).

      Outpatients diagnosed with PE at the emergency department (ED) and admitted to participating
      units represent the target population

      As the availability of DOACs may influence the duration of hospital stay, the secondary
      objectives of the present study are:

        1. to demonstrate that a shorter hospital stay for low-risk PE patients (independently on
           the method used to identify them) will reduce the incidence of hospital-associated
           complications and improve patients satisfaction and quality of life, without increasing
           the incidence of PE-related complications

        2. to demonstrate that the use of PESI, as opposed to clinical judgment alone, will be
           associated with a greater proportion of patients discharged early (< 72 hours from ED
           admission) or treated entirely at home (< 24 hours from ED admission).

        3. to demonstrate that the use of DOACs will reduce the duration of hospital stay of PE
           patients

        4. to demonstrate that the use of DOACs, as opposed to standard treatment, will be
           associated with a greater proportion of patients discharged early (< 72 hours from ED
           admission) or treated entirely at home (< 24 hours from ED admission).
STUDY DESIGN

      Within 24 hours from acute PE diagnosis, each treating physician (local Investigator) will be
      centrally randomized. Treating physicians (local Investigator) of the participating Units
      will call the coordinating centres by phone for randomization. Before randomization, in order
      to avoid any influence on treatment choice, each treating physician (local Investigator)
      should declare in advance which treatment strategy will use for his patient
      (intention-to-treat), i.e. standard treatment with heparin plus vitamin K antagonist
      (standard group) or DOACs (DOACs group) Randomization will be stratified by treatment choice
      of the local Investigator. Each of two 'intention-to-treat' approaches will be therefore
      randomized to two arms, i.e. arm 1 or arm 2.

      Arm 1: treating physicians must formally calculate PESI and report in the clinical record
      form* each day of hospitalization on top of routine clinical practice (standard care)

      Arm 2: standard care (i.e. no formally calculation of PESI on top)

      Randomization will be performed centrally with a 1:1 ratio, following a computer-generated
      list of randomization.

      STUDY POPULATION

      1.1 Population

      Randomised physicians:

      Each Local Investigator of participating canters. All participating centres are Internal
      Medicine Unit.

      PE population:

      Consecutive adult outpatients of any age, gender and race, with an objectively confirmed
      diagnosis of a suspected or unsuspected acute PE at the emergency department (ED) and
      admitted to participating units will be included.

      Suspected PE means that diagnosis has been made by an imaging test (computed tomographic
      pulmonary angiography [CTPA], pulmonary angiography, V/Q lung scan) prescribed by a treating
      physician who had clinical suspicion of PE.

      Unsuspected PE means that diagnosis has been made incidentally by an imaging test performed
      for other clinical indications (e.g. cancer staging or follow-up).

      Objective diagnosis of acute PE means: a positive computed tomographic pulmonary angiography
      (CTPA), a positive pulmonary angiography, a high-probability V/Q lung scan (or perfusion lung
      scan with negative chest X-ray), or intermediate probability V/Q or perfusion lung scan with
      proximal deep-vein thrombosis (DVT) documented by compression ultrasonography.

      1.2 Sample size calculation

      The Investigators hypothesize that the distribution of hospital stay duration for PE will
      have a standard deviation of 4 days. The I vestigators also hypothesize that the mean
      duration of hospital stay will be reduced by at least 15% in PE patients whose treating
      physician will be randomised to formally use PESI and by 5% in PE patients whose treating
      physician will not be randomised to formally calculate PESI. Low-risk PE patients are almost
      50% of all PE population. Therefore, with an α error of 0.05 and a statistical power (1-β
      error) of 80%, 200 patients for each group (a total of 400 patients) need to be enrolled to
      find a statistically significant difference (p<0.05) between the mean hospital stay length.
      As the variable 'hospital stay length' will have a non-normal distribution and needs to be
      expressed and reported as median, 10% extra patients need to be enrolled to reach a
      statistically significant difference with the previous statistical assumptions.

      Final total sample size will be, therefore, of 440 patients (220 patients for each group)

      OUTCOMES

        1. Main study parameter/endpoint

           The primary outcome is the median length of hospital stay

        2. Secondary study parameters/endpoints

      The secondary efficacy outcomes will be the following:

        1. health-system measures

             -  proportion of patients undergoing short-hospital stay

             -  proportion of patients undergoing complete home-treatment

             -  post-discharge hospital re-admission

             -  post-discharge outpatient visits to emergency department

        2. patient-related outcomes

             -  quality of life (5-point Likert scale questionnaire)

      The safety outcomes will be the following:

        1. overall mortality

        2. PE-related

             -  PE-related mortality

             -  recurrent PE and/or deep vein thrombosis (DVT)

             -  major bleeding

             -  clinically relevant non-major bleeding

             -  minor bleeding

             -  other anticoagulation-related complications (hematoma/infection at heparin or
                fondaparinux injection sites, heparin-induced thrombocytopenia)

        3. Hospitalization-related

             -  hospital-acquired infections (pneumonia; urinary tract infection; other)

             -  iatrogenic complications

             -  immobilization syndrome

             -  pressure sores

      Overall mortality, PE-related safety outcomes, post-discharge hospital re-admission and
      outpatient visits to emergency department will be measured at 14 days, 30 days, and 90 days.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Length of hospital stay
time frame: Up to 3 months
arm group label: PESI score
arm group type: Experimental
description: treating physicians must formally calculate PESI and report in the clinical record form* each day of hospitalization on top of routine clinical practice (standard care)
arm group label: Standard care
arm group type: No Intervention
description: standard care (i.e. no formally calculation of PESI on top)
intervention type: Other
intervention name: PESI score
arm group label: PESI score
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alessandro Squizzato, MD PhD
role: Principal Investigator
affiliation: Università degli Studi dell'Insubria
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: Università degli Studi dell'Insubria
investigator full name: Alessandro Squizzato
investigator title: Associate Professor
mesh term: Pulmonary Embolism
mesh term: Embolism