<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/NCT03280368</url>
  </required_header>
  <id_info>
    <org_study_id>1-16-02-191-14</org_study_id>
    <nct_id>NCT03280368</nct_id>
  </id_info>
  <brief_title>Adherence and Coagulation Assays in Dabigatran-treated Patients With Atrial Fibrillation</brief_title>
  <acronym>ARCADE</acronym>
  <official_title>Adherence and the Role of Coagulation Assays in Patients Treated With Dabigatran Etexilate for Non-valvular Atrial Fibrillation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospitalsenheden Vest</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Catharina Ziekenhuis Eindhoven</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Siemens Corporation, Corporate Technology</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Diagnostica Stago</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>European Society of Cardiology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>ANIARA</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Aarhus</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Erasmus Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospitalsenheden Vest</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In patients with non-valvular atrial fibrillation treated with dabigatran etexilate, the&#xD;
      level of adherence will be measured using a questionnaire, the Danish National Prescription&#xD;
      Registry and pillcount and will be related to plasma levels of dabigatran measured by liquid&#xD;
      chromatography tandem mass spectrometry (LC-MS/MS) and coagulation assays. The aim of the&#xD;
      study is to measure the level of adherence and evaluate the usefulness of different&#xD;
      coagulation assays to measure adherence in these patients. Furthermore, the aim is to&#xD;
      determine the correlation between the anticoagulant effect of dabigatran using different&#xD;
      coagulation assays and plasma levels of dabigatran.&#xD;
&#xD;
      Most studies so far have been performed in vitro with plasma samples spiked with dabigatran.&#xD;
      In this study the present knowledge from results of coagulation assays in dabigatran spiked&#xD;
      plasma samples will be compared to the results of coagulation assays using blood samples from&#xD;
      real-life patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2014</start_date>
  <completion_date type="Actual">January 2020</completion_date>
  <primary_completion_date type="Actual">November 2019</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>Medication adherence Stability after storage at -80 degrees C; correlation between plasma concentration and the anticoagulant effect of dabigatran</measure>
    <time_frame>2 years</time_frame>
    <description>Measured by pillcount, bloodtests, the Danish National Prescription Registry and the Morisky Medication Adherence Scale</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Patient treatment satisfaction</measure>
    <time_frame>2 years</time_frame>
    <description>Measured by the Anticlot Treatment Scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Medication persistence</measure>
    <time_frame>2 years</time_frame>
    <description>Time from start to end of dabigatran treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kidney function</measure>
    <time_frame>2 years</time_frame>
    <description>Creatinine and Glomerular Filtration Rate calculated by the Cockroft Gault formula</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Side-effects</measure>
    <time_frame>2 years</time_frame>
    <description>Bleeding, gastrointestinal side-effects</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dabigatran plasma concentrations</measure>
    <time_frame>2 years</time_frame>
    <description>Measured by liquid-chromatography tandem mass spectrometry (ng/mL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weight</measure>
    <time_frame>2 years</time_frame>
    <description>kilograms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Height</measure>
    <time_frame>2 years</time_frame>
    <description>meters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Waist circumference</measure>
    <time_frame>2 years</time_frame>
    <description>centimeters</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prothrombin time</measure>
    <time_frame>2 years</time_frame>
    <description>seconds</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Activated partial thromboplastin time</measure>
    <time_frame>2 years</time_frame>
    <description>seconds</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ROTEM</measure>
    <time_frame>2 years</time_frame>
    <description>Clotting time (seconds)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diluted thrombin time (calibrated for dabigatran)</measure>
    <time_frame>2 years</time_frame>
    <description>ng/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ecarin chromogenic assay</measure>
    <time_frame>2 years</time_frame>
    <description>ng/mL</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">430</enrollment>
  <condition>Atrial Fibrillation</condition>
  <condition>Medication Adherence</condition>
  <condition>Blood Coagulation Tests</condition>
  <condition>Anticoagulants; Circulating, Hemorrhagic Disorder</condition>
  <condition>Drug Effect</condition>
  <condition>Drug Use</condition>
  <condition>Drug Toxicity</condition>
  <condition>Drug Intolerance</condition>
  <condition>Blood Clot</condition>
  <condition>Blood Coagulation Disorder</condition>
  <condition>Laboratory Problem</condition>
  <condition>Bleeding</condition>
  <condition>Thrombosis</condition>
  <arm_group>
    <arm_group_label>A healthy volunteers</arm_group_label>
    <description>Pre-clinical study. Healthy volunteers. Plasma pooled and spiked with dabigatran. Measurement of plasma concentration of dabigatran with liquid chromatography tandem mass-spectrometry and the anticoagulant effect of dabigatran using coagulation assays.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>A patients</arm_group_label>
    <description>Pre-clinical study. Patients with atrial fibrillation treated with dabigatran etexilate.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B</arm_group_label>
    <description>Patients with an indication for treatment with dabigatran etexilate for atrial fibrillation and intended for electrocardioversion.&#xD;
Inclusion before initiation of anticoagulation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C</arm_group_label>
    <description>Patients with an indication for treatment with dabigatran etexilate for atrial fibrillation. Inclusion before initiation of anticoagulation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Bloodtest</intervention_name>
    <arm_group_label>A healthy volunteers</arm_group_label>
    <arm_group_label>A patients</arm_group_label>
    <arm_group_label>B</arm_group_label>
    <arm_group_label>C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaires</intervention_name>
    <arm_group_label>B</arm_group_label>
    <arm_group_label>C</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with atrial fibrillation with an indication for initiation of dabigatran etexilate&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 years or older&#xD;
&#xD;
          -  Non-valvular atrial fibrillation&#xD;
&#xD;
          -  Indication for dabigatran etexilate&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of anticoagulant medication within the last month&#xD;
&#xD;
          -  Contra-indication to dabigatran etexilate&#xD;
&#xD;
          -  Unable or not wishing to give informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Willemijn Comuth, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospitalsenheden Vest</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Steen Husted, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Hospitalsenheden Vest</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Unit West</name>
      <address>
        <city>Herning</city>
        <state>Mid-Jutland</state>
        <zip>7400</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <results_reference>
    <citation>Comuth WJ, de Maat MPM, van de Kerkhof D, Malczynski J, Husted S, Kristensen SD, Munster AB. Adherence to dabigatran etexilate in atrial fibrillation patients intended to undergo electrical cardioversion. Eur Heart J Cardiovasc Pharmacother. 2019 Apr 1;5(2):91-99. doi: 10.1093/ehjcvp/pvy047. Erratum In: Eur Heart J Cardiovasc Pharmacother. 2019 Apr 1;5(2):99.</citation>
    <PMID>30608563</PMID>
  </results_reference>
  <results_reference>
    <citation>Comuth WJ, Lauridsen HH, Kristensen SD, Munster AB. Translation, Cultural Adaptation, and Psychometric Properties of the Danish Version of the Anti-Clot Treatment Scale. TH Open. 2018 Sep 13;2(3):e280-e290. doi: 10.1055/s-0038-1670631. eCollection 2018 Jul.</citation>
    <PMID>31249952</PMID>
  </results_reference>
  <results_reference>
    <citation>Comuth WJ, Henriksen LO, van de Kerkhof D, Husted SE, Kristensen SD, de Maat MPM, Munster AB. Comprehensive characteristics of the anticoagulant activity of dabigatran in relation to its plasma concentration. Thromb Res. 2018 Apr;164:32-39. doi: 10.1016/j.thromres.2018.02.141. Epub 2018 Feb 17.</citation>
    <PMID>29475179</PMID>
  </results_reference>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>October 26, 2016</study_first_submitted>
  <study_first_submitted_qc>September 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>February 10, 2020</last_update_submitted>
  <last_update_submitted_qc>February 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 12, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospitalsenheden Vest</investigator_affiliation>
    <investigator_full_name>Willemijn Comuth</investigator_full_name>
    <investigator_title>Cardiologist, PhD-fellow</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Thrombosis</mesh_term>
    <mesh_term>Hemostatic Disorders</mesh_term>
    <mesh_term>Blood Coagulation Disorders</mesh_term>
    <mesh_term>Hemorrhagic Disorders</mesh_term>
    <mesh_term>Drug-Related Side Effects and Adverse Reactions</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/NCT03280368
org study id: 1-16-02-191-14
nct id: NCT03280368
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
In patients with non-valvular atrial fibrillation treated with dabigatran etexilate, the
      level of adherence will be measured using a questionnaire, the Danish National Prescription
      Registry and pillcount and will be related to plasma levels of dabigatran measured by liquid
      chromatography tandem mass spectrometry (LC-MS/MS) and coagulation assays. The aim of the
      study is to measure the level of adherence and evaluate the usefulness of different
      coagulation assays to measure adherence in these patients. Furthermore, the aim is to
      determine the correlation between the anticoagulant effect of dabigatran using different
      coagulation assays and plasma levels of dabigatran.

      Most studies so far have been performed in vitro with plasma samples spiked with dabigatran.
      In this study the present knowledge from results of coagulation assays in dabigatran spiked
      plasma samples will be compared to the results of coagulation assays using blood samples from
      real-life patients.
observational model: Cohort
time perspective: Prospective
measure: Medication adherence Stability after storage at -80 degrees C; correlation between plasma concentration and the anticoagulant effect of dabigatran
time frame: 2 years
description: Measured by pillcount, bloodtests, the Danish National Prescription Registry and the Morisky Medication Adherence Scale
measure: Patient treatment satisfaction
time frame: 2 years
description: Measured by the Anticlot Treatment Scale
measure: Medication persistence
time frame: 2 years
description: Time from start to end of dabigatran treatment
measure: Kidney function
time frame: 2 years
description: Creatinine and Glomerular Filtration Rate calculated by the Cockroft Gault formula
measure: Side-effects
time frame: 2 years
description: Bleeding, gastrointestinal side-effects
measure: Dabigatran plasma concentrations
time frame: 2 years
description: Measured by liquid-chromatography tandem mass spectrometry (ng/mL)
measure: Weight
time frame: 2 years
description: kilograms
measure: Height
time frame: 2 years
description: meters
measure: Waist circumference
time frame: 2 years
description: centimeters
measure: Prothrombin time
time frame: 2 years
description: seconds
measure: Activated partial thromboplastin time
time frame: 2 years
description: seconds
measure: ROTEM
time frame: 2 years
description: Clotting time (seconds)
measure: Diluted thrombin time (calibrated for dabigatran)
time frame: 2 years
description: ng/mL
measure: Ecarin chromogenic assay
time frame: 2 years
description: ng/mL
arm group label: A healthy volunteers
description: Pre-clinical study. Healthy volunteers. Plasma pooled and spiked with dabigatran. Measurement of plasma concentration of dabigatran with liquid chromatography tandem mass-spectrometry and the anticoagulant effect of dabigatran using coagulation assays.
arm group label: A patients
description: Pre-clinical study. Patients with atrial fibrillation treated with dabigatran etexilate.
arm group label: B
description: Patients with an indication for treatment with dabigatran etexilate for atrial fibrillation and intended for electrocardioversion.
Inclusion before initiation of anticoagulation.
arm group label: C
description: Patients with an indication for treatment with dabigatran etexilate for atrial fibrillation. Inclusion before initiation of anticoagulation.
intervention type: Other
intervention name: Bloodtest
arm group label: A healthy volunteers
arm group label: A patients
arm group label: B
arm group label: C
intervention type: Other
intervention name: Questionnaires
arm group label: B
arm group label: C
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Willemijn Comuth, MD
role: Principal Investigator
affiliation: Hospitalsenheden Vest
last name: Steen Husted, MD, PhD
role: Study Chair
affiliation: Hospitalsenheden Vest
facility: 
country: Denmark
citation: Comuth WJ, de Maat MPM, van de Kerkhof D, Malczynski J, Husted S, Kristensen SD, Munster AB. Adherence to dabigatran etexilate in atrial fibrillation patients intended to undergo electrical cardioversion. Eur Heart J Cardiovasc Pharmacother. 2019 Apr 1;5(2):91-99. doi: 10.1093/ehjcvp/pvy047. Erratum In: Eur Heart J Cardiovasc Pharmacother. 2019 Apr 1;5(2):99.
PMID: 30608563
citation: Comuth WJ, Lauridsen HH, Kristensen SD, Munster AB. Translation, Cultural Adaptation, and Psychometric Properties of the Danish Version of the Anti-Clot Treatment Scale. TH Open. 2018 Sep 13;2(3):e280-e290. doi: 10.1055/s-0038-1670631. eCollection 2018 Jul.
PMID: 31249952
citation: Comuth WJ, Henriksen LO, van de Kerkhof D, Husted SE, Kristensen SD, de Maat MPM, Munster AB. Comprehensive characteristics of the anticoagulant activity of dabigatran in relation to its plasma concentration. Thromb Res. 2018 Apr;164:32-39. doi: 10.1016/j.thromres.2018.02.141. Epub 2018 Feb 17.
PMID: 29475179
responsible party type: Principal Investigator
investigator affiliation: Hospitalsenheden Vest
investigator full name: Willemijn Comuth
investigator title: Cardiologist, PhD-fellow
mesh term: Atrial Fibrillation
mesh term: Thrombosis
mesh term: Hemostatic Disorders
mesh term: Blood Coagulation Disorders
mesh term: Hemorrhagic Disorders
mesh term: Drug-Related Side Effects and Adverse Reactions
sharing ipd: No