<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/NCT03274401</url>
  </required_header>
  <id_info>
    <org_study_id>SAFE-PE</org_study_id>
    <nct_id>NCT03274401</nct_id>
  </id_info>
  <brief_title>Screening for Atrial Fibrillation in Pulmonary Embolism Study -SAFE-PE Study</brief_title>
  <acronym>SAFE-PE</acronym>
  <official_title>Screening for Atrial Fibrillation in Pulmonary Embolism Study - SAFE-PE Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Danderyd Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Karolinska Institutet</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Danderyd Hospital</source>
  <oversight_info>
    <has_dmc>No</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>
      Patients with newly diagnosed pulmonary embolism and high thromboembolic risk will be&#xD;
      randomized to screening for atrial fibrillation or standard of care using intermittent ECG&#xD;
      registration for at least two weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients included in the study might be referred for an ultrasound of deep vein thrombosis&#xD;
      unless this has already been performed. Blood will be drawn in a subset of patients to assess&#xD;
      cardiac biomarkers, and stored in a biobank for further analysis of thrombotic biomarkers. If&#xD;
      a computed tomography (CT) angiogram was used as diagnostic method for pulmonary embolism a&#xD;
      radiologic review will be performed to assess presence of right atrium thrombus, with the&#xD;
      reviewer will be blinded to the presence of atrial fibrillation (AF). In addition, an&#xD;
      echocardiogram of the heart will be performed.&#xD;
&#xD;
      Many patients with pulmonary embolism have prolonged symptoms of dyspnoea, and palpitations.&#xD;
      These symptoms are also described in patients with atrial fibrillation. All participants will&#xD;
      be asked to fill out a standardized quality of life (RAND-36)-, and a symptoms questionnaire&#xD;
      (modified European Heart Rhythm association symptom scale). Upon inclusion all patients will&#xD;
      be reviewed for factors predisposing to PE such as recent surgery, or illness requiring&#xD;
      immobilisation within the past three months prior to index event.&#xD;
&#xD;
      After inclusion patients will be randomised to screening for atrial fibrillation or standard&#xD;
      of care. Participants who get randomised into the screening arm will be screened for AF using&#xD;
      a validated, handheld ECG device at least twice daily for two weeks. Participants who get AF&#xD;
      diagnosed during the study will be referred for appropriate cardiology follow-up and the&#xD;
      anticoagulant therapy will be changed from a fixed time to continued (subject to yearly&#xD;
      reviews). Patients will then be followed for five years using the Swedish death registry, and&#xD;
      the Swedish national patient registry, in combination with the national prescription registry&#xD;
      for the outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Due to Covid-19&#xD;
  </why_stopped>
  <start_date type="Actual">September 13, 2017</start_date>
  <completion_date type="Actual">April 1, 2022</completion_date>
  <primary_completion_date type="Actual">December 31, 2020</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>
    <intervention_model_description>Patients with newly diagnosed pulmonary embolism will be randomized to screening for atrial fibrillation or standard of care</intervention_model_description>
    <primary_purpose>Screening</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mortality</measure>
    <time_frame>5 years after intervention</time_frame>
    <description>Mortality in the screening arm compared to the control arm</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mortality and thromboembolic events</measure>
    <time_frame>5 years after intervention</time_frame>
    <description>Combined endpoint of mortality and thromboembolic events (stroke, transient ischemic attack, systemic embolism, deep vein thrombosis and pulmonary embolism) in the screening arm compared to the control arm</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Quality of life using RAND-36</measure>
    <time_frame>1 year after inclusion</time_frame>
    <description>All patients will fill in a quality of life questionnaire (RAND-36). Quality of life will be compared in patients where AF is detected compared to the group where AF is not detected in patients with PE. Quality of life will be measured using a RAND-36 questionnaire that uses questions regarding physical, mental and social wellbeing based on the World Health Organization's definition of health.</description>
  </other_outcome>
  <other_outcome>
    <measure>Quality of life using EHRA symptom scale</measure>
    <time_frame>1 year after inclusion</time_frame>
    <description>Quality of life will be compared in patients where AF is detected compared to the group where AF is not detected. Quality of life will be measured using a modified European Heart Rhythm association (EHRA) symptom scale and reported as a separate outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Assessment of clinical risk factors for atrial fibrillation in patients with pulmonary embolism</measure>
    <time_frame>1 year after inclusion</time_frame>
    <description>Comparison of clinical characteristics (diagnosis of prior hypertension, diabetes mellitus type 2, vascular disease, heart failure, stroke/TIA) to identify risk factors for detection of AF in patients with PE, and use to build a risk score for AF detection. Patients in the intervention arm who had atrial fibrillation discovered after screening with intermittent ECG will be compared to participants in the intervention arm where atrial fibrillation was not discovered. Multivariable logistic regression will be used to determine which risk factors are most important in order to detect previously undetected AF in patients with pulmonary embolism.</description>
  </other_outcome>
  <other_outcome>
    <measure>Biomarkers as a prediction of diagnosis in pulmonary embolism</measure>
    <time_frame>5 years after inclusion</time_frame>
    <description>The use of biomarkers to predict risk of future thromboembolic events and mortality in patients with PE. Blood will be collected from the majority of participants in the stuydy and stored in a biobank. Different biomarkers will be measured (for instance NT-proBNP, troponin, CRP and thromboembolic biomarkers) and the association between the levels of biomarkers and mortality, and thromboembolic morbitidy will be analysed using Cox proportional regression models.</description>
  </other_outcome>
  <other_outcome>
    <measure>The association between biomarkers and newly detected AF in patients with pulmonary embolism</measure>
    <time_frame>1 years after inclusion</time_frame>
    <description>Biomarkers will be collected in the majority of patients. The levels of various biomarkers in the intervention group where AF was detected will be compared to participants in the intervention group where AF was not detected. Multivariable logistic regression will be used to study the association between biomarkers and the detection of AF in patients with PE.</description>
  </other_outcome>
  <other_outcome>
    <measure>Echocardiographic measures and their association with outcome in patients with PE</measure>
    <time_frame>5 years after inclusion</time_frame>
    <description>Various echocardiographic parameters will be measured in all included patients. The echocardiographic measures in patients in the study who had a secondary outcome will be compared to patients who did not have a secondary outcome. Echocardiographic measures will be analysed using multivariable Cox regression analysis in order to find parameters that are associated with poor outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Echocardiographic parameters and their association with newly detected AF in patients with PE</measure>
    <time_frame>1 years after inclusion</time_frame>
    <description>In the intervention arm echocardiographic parameters will be compared for the group where AF was detected compared to the group where AF was not detected. Using multivariable logistic regression echocardiographic variables associated with the detection of atrial fibrillation in patients with pulmonary embolism will be studied.</description>
  </other_outcome>
  <other_outcome>
    <measure>Presence of right atrial thrombus on DT angiography in PE</measure>
    <time_frame>5 years after inclusion</time_frame>
    <description>In participants where DT angiography was used in order to diagnose PE the images will be reviewed in order assess whether a right atrial thrombi could be detected. The outcome between participants with right atrial thrombus on DT angiography will be compared to participants who did not have right atrial thrombus on DT.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">90</enrollment>
  <condition>Atrial Fibrillation</condition>
  <condition>Pulmonary Embolism</condition>
  <arm_group>
    <arm_group_label>Screening Arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Screening for atrial fibrillation using a hand-held ECG device (Zenicor intermittent ECG) at least twice daily for two weeks. In patients where AF is detected prolonged OAC therapy will be administered.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Standard of care</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Zenicor intermittent ECG device</intervention_name>
    <description>At least two weeks of screening twice daily for atrial fibrillation using intermittent ECG recordings, and prolonged use of OAC-therapy if atrial fibrillation is detected</description>
    <arm_group_label>Screening Arm</arm_group_label>
    <other_name>Oral anticoagulant therapy prolonged (if AF detected)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>5 day ECG patch</intervention_name>
    <description>Selection of device for monitoring clinicians' choice</description>
    <arm_group_label>Screening Arm</arm_group_label>
    <other_name>Oral anticoagulant therapy prolonged if AF detected</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Recent pulmonary embolism (within three months)&#xD;
&#xD;
        Fulfilling Chads-Vasc criteria for life-long oral anticoagulant therapy (2 points for men,&#xD;
        and 3 points for women), or age &gt; 65 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known diagnosis of atrial fibrillation Contra-indication to oral anticoagulant therapy&#xD;
             Provoked pulmonary embolism in sub-segmental artery only Active cancer therapy&#xD;
             (on-going therapy, recent surgery or life-expectancy below 1 year)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Håkan Wallén, MD PhD</last_name>
    <role>Study Director</role>
    <affiliation>Karolinska Institutet - Danderyd Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Emma Svennberg, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Karolinska Institutet - Danderyd Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Danderyd Hospital</name>
      <address>
        <city>Stockholm</city>
        <zip>182 88</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>August 24, 2017</study_first_submitted>
  <study_first_submitted_qc>September 3, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>July 26, 2022</last_update_submitted>
  <last_update_submitted_qc>July 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Atrial fibrillation</keyword>
  <keyword>Pulmonary embolism</keyword>
  <keyword>Screening</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Embolism</mesh_term>
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Embolism</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anticoagulants</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03274401
org study id: SAFE-PE
nct id: NCT03274401
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Patients with newly diagnosed pulmonary embolism and high thromboembolic risk will be
      randomized to screening for atrial fibrillation or standard of care using intermittent ECG
      registration for at least two weeks.
Patients included in the study might be referred for an ultrasound of deep vein thrombosis
      unless this has already been performed. Blood will be drawn in a subset of patients to assess
      cardiac biomarkers, and stored in a biobank for further analysis of thrombotic biomarkers. If
      a computed tomography (CT) angiogram was used as diagnostic method for pulmonary embolism a
      radiologic review will be performed to assess presence of right atrium thrombus, with the
      reviewer will be blinded to the presence of atrial fibrillation (AF). In addition, an
      echocardiogram of the heart will be performed.

      Many patients with pulmonary embolism have prolonged symptoms of dyspnoea, and palpitations.
      These symptoms are also described in patients with atrial fibrillation. All participants will
      be asked to fill out a standardized quality of life (RAND-36)-, and a symptoms questionnaire
      (modified European Heart Rhythm association symptom scale). Upon inclusion all patients will
      be reviewed for factors predisposing to PE such as recent surgery, or illness requiring
      immobilisation within the past three months prior to index event.

      After inclusion patients will be randomised to screening for atrial fibrillation or standard
      of care. Participants who get randomised into the screening arm will be screened for AF using
      a validated, handheld ECG device at least twice daily for two weeks. Participants who get AF
      diagnosed during the study will be referred for appropriate cardiology follow-up and the
      anticoagulant therapy will be changed from a fixed time to continued (subject to yearly
      reviews). Patients will then be followed for five years using the Swedish death registry, and
      the Swedish national patient registry, in combination with the national prescription registry
      for the outcomes.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Patients with newly diagnosed pulmonary embolism will be randomized to screening for atrial fibrillation or standard of care
primary purpose: Screening
masking: None (Open Label)
measure: Mortality
time frame: 5 years after intervention
description: Mortality in the screening arm compared to the control arm
measure: Mortality and thromboembolic events
time frame: 5 years after intervention
description: Combined endpoint of mortality and thromboembolic events (stroke, transient ischemic attack, systemic embolism, deep vein thrombosis and pulmonary embolism) in the screening arm compared to the control arm
measure: Quality of life using RAND-36
time frame: 1 year after inclusion
description: All patients will fill in a quality of life questionnaire (RAND-36). Quality of life will be compared in patients where AF is detected compared to the group where AF is not detected in patients with PE. Quality of life will be measured using a RAND-36 questionnaire that uses questions regarding physical, mental and social wellbeing based on the World Health Organization's definition of health.
measure: Quality of life using EHRA symptom scale
time frame: 1 year after inclusion
description: Quality of life will be compared in patients where AF is detected compared to the group where AF is not detected. Quality of life will be measured using a modified European Heart Rhythm association (EHRA) symptom scale and reported as a separate outcome.
measure: Assessment of clinical risk factors for atrial fibrillation in patients with pulmonary embolism
time frame: 1 year after inclusion
description: Comparison of clinical characteristics (diagnosis of prior hypertension, diabetes mellitus type 2, vascular disease, heart failure, stroke/TIA) to identify risk factors for detection of AF in patients with PE, and use to build a risk score for AF detection. Patients in the intervention arm who had atrial fibrillation discovered after screening with intermittent ECG will be compared to participants in the intervention arm where atrial fibrillation was not discovered. Multivariable logistic regression will be used to determine which risk factors are most important in order to detect previously undetected AF in patients with pulmonary embolism.
measure: Biomarkers as a prediction of diagnosis in pulmonary embolism
time frame: 5 years after inclusion
description: The use of biomarkers to predict risk of future thromboembolic events and mortality in patients with PE. Blood will be collected from the majority of participants in the stuydy and stored in a biobank. Different biomarkers will be measured (for instance NT-proBNP, troponin, CRP and thromboembolic biomarkers) and the association between the levels of biomarkers and mortality, and thromboembolic morbitidy will be analysed using Cox proportional regression models.
measure: The association between biomarkers and newly detected AF in patients with pulmonary embolism
time frame: 1 years after inclusion
description: Biomarkers will be collected in the majority of patients. The levels of various biomarkers in the intervention group where AF was detected will be compared to participants in the intervention group where AF was not detected. Multivariable logistic regression will be used to study the association between biomarkers and the detection of AF in patients with PE.
measure: Echocardiographic measures and their association with outcome in patients with PE
time frame: 5 years after inclusion
description: Various echocardiographic parameters will be measured in all included patients. The echocardiographic measures in patients in the study who had a secondary outcome will be compared to patients who did not have a secondary outcome. Echocardiographic measures will be analysed using multivariable Cox regression analysis in order to find parameters that are associated with poor outcome.
measure: Echocardiographic parameters and their association with newly detected AF in patients with PE
time frame: 1 years after inclusion
description: In the intervention arm echocardiographic parameters will be compared for the group where AF was detected compared to the group where AF was not detected. Using multivariable logistic regression echocardiographic variables associated with the detection of atrial fibrillation in patients with pulmonary embolism will be studied.
measure: Presence of right atrial thrombus on DT angiography in PE
time frame: 5 years after inclusion
description: In participants where DT angiography was used in order to diagnose PE the images will be reviewed in order assess whether a right atrial thrombi could be detected. The outcome between participants with right atrial thrombus on DT angiography will be compared to participants who did not have right atrial thrombus on DT.
arm group label: Screening Arm
arm group type: Active Comparator
description: Screening for atrial fibrillation using a hand-held ECG device (Zenicor intermittent ECG) at least twice daily for two weeks. In patients where AF is detected prolonged OAC therapy will be administered.
arm group label: Control Arm
arm group type: No Intervention
description: Standard of care
intervention type: Device
intervention name: Zenicor intermittent ECG device
description: At least two weeks of screening twice daily for atrial fibrillation using intermittent ECG recordings, and prolonged use of OAC-therapy if atrial fibrillation is detected
arm group label: Screening Arm
other name: Oral anticoagulant therapy prolonged (if AF detected)
intervention type: Device
intervention name: 5 day ECG patch
description: Selection of device for monitoring clinicians' choice
arm group label: Screening Arm
other name: Oral anticoagulant therapy prolonged if AF detected
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Håkan Wallén, MD PhD
role: Study Director
affiliation: Karolinska Institutet - Danderyd Hospital
last name: Emma Svennberg, MD PhD
role: Principal Investigator
affiliation: Karolinska Institutet - Danderyd Hospital
facility: 
country: Sweden
responsible party type: Sponsor
mesh term: Pulmonary Embolism
mesh term: Atrial Fibrillation
mesh term: Embolism
mesh term: Anticoagulants
sharing ipd: No