<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/NCT03301935</url>
  </required_header>
  <id_info>
    <org_study_id>RASAP</org_study_id>
    <nct_id>NCT03301935</nct_id>
  </id_info>
  <brief_title>Risk Assessment in Patients With Symptomatic- and Asymptomatic Preexcitation</brief_title>
  <acronym>RASAP</acronym>
  <official_title>Risk Assessment in Patients With Symptomatic- and Asymptomatic Preexcitation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Karolinska University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Karolinska University 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>
      Prospective cohort study including 150 patients with pre-excitation on ECG referred to our&#xD;
      clinic for risk assessment. There will be equal numbers of symptomatic and asymptomatic&#xD;
      patients included in the study. Each patient will perform an exercise stress test on bicycle&#xD;
      before an invasive electrophysiological test. The purpose of this study is to compare&#xD;
      exercise stress testing on bicycle to an invasive electrophysiological study, regarding risk&#xD;
      assessment of patients with pre-excitation. The electrophysiology study is set as reference.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hypothesis:&#xD;
&#xD;
      The sensitivity and specificity for exercise stress test (bicycle) is low in identifying&#xD;
      patients with benign accessory pathways and cannot replace an invasive electrophysiological&#xD;
      study in risk assessment of symptomatic and asymptomatic patients with pre-excitation.&#xD;
      Invasive electrophysiological assessment should be recommended for all patients with&#xD;
      pre-excitation despite symptoms or documented arrhythmia.&#xD;
&#xD;
      Methods:&#xD;
&#xD;
      Prospective cohort study including 150 patients with pre-excitation on ECG referred to our&#xD;
      clinic for risk assessment. There will be equal numbers of symptomatic and asymptomatic&#xD;
      patients included in the study. Each patient will perform an exercise stress test on bicycle&#xD;
      before an invasive electrophysiological test. The purpose of this study is to compare&#xD;
      exercise stress testing on bicycle to an invasive electrophysiological study, regarding risk&#xD;
      assessment of patients with pre-excitation. The electrophysiology study is set as reference.&#xD;
&#xD;
      A. Instruments and methods for analysis:&#xD;
&#xD;
        -  All patients will perform an exercise stress test on a test bike according to standard&#xD;
           protocol. ECG will be monitored closely regarding loss of pre-excitation during&#xD;
           exercise.&#xD;
&#xD;
        -  After exercise testing all patients will undergo an invasive electrophysiological study&#xD;
           according to standard protocol.&#xD;
&#xD;
      This procedure is set as reference in identifying potentially dangerous accessory pathways.&#xD;
&#xD;
        -  APERP as well as shortest R-R interval during atrial fibrillation, when applicable, will&#xD;
           be used to characterize the conduction properties of the pathway defining high risk&#xD;
           pathway with APERP ≤ 250 ms with or without isoprenaline.&#xD;
&#xD;
        -  Inducibility in AVRT (orthodromic or antidromic reentry tachycardia) and atrial&#xD;
           fibrillation will be recorded as well as tachycardia cycle length.&#xD;
&#xD;
        -  The results of the two tests will be compared with each patient being their own control.&#xD;
&#xD;
      Programmed stimulation for risk assessment in patients with pre-excitation/accessory&#xD;
      pathways:&#xD;
&#xD;
        1. AV block or block in AP during IAP, ms&#xD;
&#xD;
        2. VA block or block in AP during IVP, ms&#xD;
&#xD;
        3. Antegrade curve (single ES 600 ms or longer and 400 ms): APERP And AVNERP&#xD;
&#xD;
        4. Retrograde curve (single ES 600 ms): Retrograde APERP and AVNERP&#xD;
&#xD;
        5. Tachycardia induction (Double ES from atrium): Inducibility&#xD;
&#xD;
        6. Burst pacing from atrium&#xD;
&#xD;
        7. Isoprenaline: Dose adjustment until heart rate&gt;100/min or &gt;50% increase from basal&#xD;
           level.&#xD;
&#xD;
             -  Antegrade curve during isoprenaline: APERP, AVNERP&#xD;
&#xD;
             -  Retrograde curve during Isoprenaline:&#xD;
&#xD;
      Retrograde APERP and AVNERP&#xD;
&#xD;
      - Tachycardia induction during Isoprenaline&#xD;
&#xD;
      Statistical analysis: Sensitivity, specificity, positive predictive value and negative&#xD;
      predictive value of exercise stress test will be assessed, using the electrophysiological&#xD;
      study as a reference standard. A true positive and a false negative will be defined,&#xD;
      respectively, as the persistence and the disappearance of pre-excitation in the symptomatic&#xD;
      and asymptomatic group. A true negative and a false positive will be defined, respectively,&#xD;
      as the disappearance and the persistence of pre-excitation in the symptomatic and&#xD;
      asymptomatic group. Moreover, we will consider the shortest value between the minimum RR&#xD;
      interval during atrial fibrillation and accessory pathway anterograde effective refractory&#xD;
      period (APERP) in each patient and look for the value that could be predicted by noninvasive&#xD;
      tests with the best combination of sensitivity, specificity, positive and negative predictive&#xD;
      value.&#xD;
&#xD;
      Chi Square statistics will be used in comparing categorical data such as inducibility and&#xD;
      tachycardia cycle length.&#xD;
&#xD;
      B. Calculation of power: With the planned number of patients, 150, a 10% difference should be&#xD;
      detected with a power of 80% at α 0,1.&#xD;
&#xD;
      C. Expected results: We expect exercise testing to have high sensitivity, but low specificity&#xD;
      and a low positive predictive value.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 1, 2016</start_date>
  <completion_date type="Actual">January 31, 2022</completion_date>
  <primary_completion_date type="Actual">January 31, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>RASAP</measure>
    <time_frame>Approximately 1 year from inclusion to 6 months follow-up.</time_frame>
    <description>Number of potentially dangerous pathways (i.e APERP &lt;250 ms) identified by exercise stress test compared to the invasive electrophysiological test in the symptomatic- and asymptomatic Group.</description>
  </primary_outcome>
  <enrollment type="Actual">168</enrollment>
  <condition>Wolff-Parkinson-White Syndrome</condition>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Electrophysiology testing and exercise stress testing</intervention_name>
    <description>Each patient will perform an exercise stress test on bicycle before an invasive electrophysiological test. Both examinations will be performed according to current Clinical practice.</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        All patients with documented ventricular preexcitation, referred for risk assessment to the&#xD;
        Arrhythmia department at Karolinska University Hospital, were asked to participate in the&#xD;
        study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ventricular pre exciatation on 12 lead ECG&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to perform invasive electrophysiology testing or exercise stress test on&#xD;
             bicycle.&#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>Mats Jensen-Urstad, Professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Karolinska Institutet</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Karolinska University Hospital</name>
      <address>
        <city>Stockholm</city>
        <zip>SE-14186</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>February 23, 2017</study_first_submitted>
  <study_first_submitted_qc>September 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 4, 2017</study_first_posted>
  <last_update_submitted>May 21, 2022</last_update_submitted>
  <last_update_submitted_qc>May 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Karolinska University Hospital</investigator_affiliation>
    <investigator_full_name>Mats Jensen-Urstad</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Risk assessment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Wolff-Parkinson-White Syndrome</mesh_term>
  </condition_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/NCT03301935
org study id: RASAP
nct id: NCT03301935
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Prospective cohort study including 150 patients with pre-excitation on ECG referred to our
      clinic for risk assessment. There will be equal numbers of symptomatic and asymptomatic
      patients included in the study. Each patient will perform an exercise stress test on bicycle
      before an invasive electrophysiological test. The purpose of this study is to compare
      exercise stress testing on bicycle to an invasive electrophysiological study, regarding risk
      assessment of patients with pre-excitation. The electrophysiology study is set as reference.
Hypothesis:

      The sensitivity and specificity for exercise stress test (bicycle) is low in identifying
      patients with benign accessory pathways and cannot replace an invasive electrophysiological
      study in risk assessment of symptomatic and asymptomatic patients with pre-excitation.
      Invasive electrophysiological assessment should be recommended for all patients with
      pre-excitation despite symptoms or documented arrhythmia.

      Methods:

      Prospective cohort study including 150 patients with pre-excitation on ECG referred to our
      clinic for risk assessment. There will be equal numbers of symptomatic and asymptomatic
      patients included in the study. Each patient will perform an exercise stress test on bicycle
      before an invasive electrophysiological test. The purpose of this study is to compare
      exercise stress testing on bicycle to an invasive electrophysiological study, regarding risk
      assessment of patients with pre-excitation. The electrophysiology study is set as reference.

      A. Instruments and methods for analysis:

        -  All patients will perform an exercise stress test on a test bike according to standard
           protocol. ECG will be monitored closely regarding loss of pre-excitation during
           exercise.

        -  After exercise testing all patients will undergo an invasive electrophysiological study
           according to standard protocol.

      This procedure is set as reference in identifying potentially dangerous accessory pathways.

        -  APERP as well as shortest R-R interval during atrial fibrillation, when applicable, will
           be used to characterize the conduction properties of the pathway defining high risk
           pathway with APERP ≤ 250 ms with or without isoprenaline.

        -  Inducibility in AVRT (orthodromic or antidromic reentry tachycardia) and atrial
           fibrillation will be recorded as well as tachycardia cycle length.

        -  The results of the two tests will be compared with each patient being their own control.

      Programmed stimulation for risk assessment in patients with pre-excitation/accessory
      pathways:

        1. AV block or block in AP during IAP, ms

        2. VA block or block in AP during IVP, ms

        3. Antegrade curve (single ES 600 ms or longer and 400 ms): APERP And AVNERP

        4. Retrograde curve (single ES 600 ms): Retrograde APERP and AVNERP

        5. Tachycardia induction (Double ES from atrium): Inducibility

        6. Burst pacing from atrium

        7. Isoprenaline: Dose adjustment until heart rate>100/min or >50% increase from basal
           level.

             -  Antegrade curve during isoprenaline: APERP, AVNERP

             -  Retrograde curve during Isoprenaline:

      Retrograde APERP and AVNERP

      - Tachycardia induction during Isoprenaline

      Statistical analysis: Sensitivity, specificity, positive predictive value and negative
      predictive value of exercise stress test will be assessed, using the electrophysiological
      study as a reference standard. A true positive and a false negative will be defined,
      respectively, as the persistence and the disappearance of pre-excitation in the symptomatic
      and asymptomatic group. A true negative and a false positive will be defined, respectively,
      as the disappearance and the persistence of pre-excitation in the symptomatic and
      asymptomatic group. Moreover, we will consider the shortest value between the minimum RR
      interval during atrial fibrillation and accessory pathway anterograde effective refractory
      period (APERP) in each patient and look for the value that could be predicted by noninvasive
      tests with the best combination of sensitivity, specificity, positive and negative predictive
      value.

      Chi Square statistics will be used in comparing categorical data such as inducibility and
      tachycardia cycle length.

      B. Calculation of power: With the planned number of patients, 150, a 10% difference should be
      detected with a power of 80% at α 0,1.

      C. Expected results: We expect exercise testing to have high sensitivity, but low specificity
      and a low positive predictive value.
observational model: Cohort
time perspective: Prospective
measure: RASAP
time frame: Approximately 1 year from inclusion to 6 months follow-up.
description: Number of potentially dangerous pathways (i.e APERP <250 ms) identified by exercise stress test compared to the invasive electrophysiological test in the symptomatic- and asymptomatic Group.
intervention type: Procedure
intervention name: Electrophysiology testing and exercise stress testing
description: Each patient will perform an exercise stress test on bicycle before an invasive electrophysiological test. Both examinations will be performed according to current Clinical practice.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Mats Jensen-Urstad, Professor
role: Principal Investigator
affiliation: Karolinska Institutet
facility: 
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Karolinska University Hospital
investigator full name: Mats Jensen-Urstad
investigator title: Professor
mesh term: Wolff-Parkinson-White Syndrome
sharing ipd: No