<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/NCT03759691</url>
  </required_header>
  <id_info>
    <org_study_id>030683</org_study_id>
    <nct_id>NCT03759691</nct_id>
  </id_info>
  <brief_title>Predictors for Prehospital Delay in Stroke Treatment</brief_title>
  <official_title>Stroke Awareness and Help-seeking Behaviour: Predictors for Prehospital Delay in Stroke Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Aarhus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Aarhus University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Research Unit for General Practice, Aarhus University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Regional Hospital West Jutland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>TrygFonden, Denmark</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Aarhus</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>
      Stroke is the second-leading cause of death worldwide and a leading cause of long-term&#xD;
      disability. Annually 12,000 people in Denmark suffers a stroke; half of them will have&#xD;
      long-term disabilities that may affect the activities of daily living. In addition to&#xD;
      substantial individual suffering, stroke is also associated with considerable costs to&#xD;
      society. Acute reperfusion therapies started within 4.5 to 6 hours (in some up to 24 hours)&#xD;
      from symptom onset for acute ischaemic stroke (AIS) have revolutionized the acute stroke&#xD;
      treatment and considerably improved the overall prognosis and mortality. However, only 15-25%&#xD;
      of Danish patients are eligible to acute treatment. Numerous attempts to reduce both&#xD;
      prehospital and in-hospital delay in stroke have been made, but much time is still lost in&#xD;
      the prehospital phase.&#xD;
&#xD;
      Many stroke patients do not recognize their own symptoms as signs of a stroke or do not&#xD;
      understand the importance of calling Emergecy Medical Services (EMS) immediately. Others&#xD;
      cannot call for help unless they have a bystander, because of cognitive impairment or&#xD;
      aphasia. Some patients have a wait-and-see attitude, contact their GP or out-of-hours GP,&#xD;
      which also can increase the delay. Educational stroke campaigns can increase knowledge,&#xD;
      improve help-seeking behaviour and increase the number of patients eligible for reperfusion&#xD;
      therapies. The foundation TrygFonden is planning a national stroke campaign in 2019.&#xD;
&#xD;
      Aims:&#xD;
&#xD;
        1. To explore the knowledge of stroke in stroke patients and bystanders.&#xD;
&#xD;
        2. To explore the process from onset of symptoms until admission to hospital and the&#xD;
           reasons for prehospital delay.&#xD;
&#xD;
        3. To explore the association between stroke knowledge, help-seeking behaviour and&#xD;
           receiving revascularization therapy.&#xD;
&#xD;
        4. To evaluate the immediate effect of the national campaign six months after initiation.&#xD;
&#xD;
      Material and methods:&#xD;
&#xD;
      Study 1:&#xD;
&#xD;
      Structured interviews of stroke patients (and bystanders) admitted to the Department of&#xD;
      Neurology at Aarhus University Hospital and Regional Hospital West Jutland (Holstebro). The&#xD;
      investigators will use the patient's medical record (EPJ) and the Danish Stroke Register&#xD;
      (DSR) and map the patient's route from onset of symptoms to admission to stroke centre,&#xD;
      including contact to general practitioner (GP), out-of-hours GP or Emergency Medical Services&#xD;
      (EMS). For patients who have been in contact with their GP, the GP will receive an electronic&#xD;
      questionnaire to explore the time- and event pathway from first contact until admitting the&#xD;
      patient to hospital. The investigators will interview 500 patients and approximately 300&#xD;
      bystanders over a period of 3 months.&#xD;
&#xD;
      Study 2:&#xD;
&#xD;
      The investigators will evaluate the effect of the national stroke campaign by conducting a&#xD;
      similar study in 2020 when the campaign has been running for six months.&#xD;
&#xD;
      Perspectives:&#xD;
&#xD;
      This study will provide new information about stroke patients and bystanders, their knowledge&#xD;
      of stroke and their help-seeking behaviour. If more knowledge about the factors that cause&#xD;
      prehospital delay in stroke treatment are obtained, the investigators will know which areas&#xD;
      to focus on in the future to improve the outcome for stroke patients. Part of this project&#xD;
      will examine the effect of TrygFondens national stroke campaign, which is expected to have&#xD;
      impact on general knowledge and help-seeking behaviour. If more people know the core symptoms&#xD;
      of stroke, hopefully more people will also know how to react to these symptoms by calling&#xD;
      EMS. This will eventually increase reperfusion therapy rates, considerably improve stroke&#xD;
      morbidity and mortality and reduce both individual suffering and the societal costs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Stroke awareness and help-seeking behaviour: predictors for prehospital delay in stroke&#xD;
      treatment&#xD;
&#xD;
      Ane Bull Iversen, MD Section for General Medical Practice Department of Public Health and&#xD;
      Department of Neurology Department of Clinical Medicine Aarhus University&#xD;
&#xD;
      Supervisors:&#xD;
&#xD;
      Professor Bo Christensen, PhD, MD Section for General Medical Practice Department of Public&#xD;
      Health Aarhus University&#xD;
&#xD;
      Professor Grethe Andersen, PhD, MD Department of Neurology Department of Clinical Medicine&#xD;
      Aarhus University&#xD;
&#xD;
      Senior researcher Morten Bondo Christensen, PhD, MD Research Unit for General Practice&#xD;
      Department of Public Health Aarhus University&#xD;
&#xD;
      Professor Søren Paaske Johnsen, PhD, MD Center for Clinical Health Services Research&#xD;
      Department of Clinical Medicine Aalborg University and Aalborg University Hospital&#xD;
&#xD;
      Background Stroke is the second-leading cause of death worldwide and a leading cause of&#xD;
      long-term disability. Each year 12,000 people in Denmark are hit by a stroke. In addition to&#xD;
      substantial individual suffering, stroke is also associated with considerable costs to&#xD;
      society.&#xD;
&#xD;
      The World Health Organization (WHO) has estimated a marked increase in the stroke prevalence&#xD;
      in 2025 as a result of ageing populations. This development will increase the need to&#xD;
      identify areas with potential for improvement in the treatment of stroke. Acute reperfusion&#xD;
      therapies started within 4.5 to 6 hours (in some up to 24 hours) from symptom onset for AIS&#xD;
      have revolutionized the acute stroke treatment and considerably improved the overall&#xD;
      prognosis and mortality. However, only 15-25% of Danish patients are eligible to acute&#xD;
      treatment. This is primarily due to presentation outside the time window for intravenous&#xD;
      thrombolysis and endo¬vascular treatment at the stroke centre. Time is also of utmost&#xD;
      importance in patients receiving reperfusions therapies, as the chance of functional&#xD;
      independence decreases rapidly during the first few hours after stroke onset.&#xD;
&#xD;
      Numerous attempts have been made to reduce both prehospital and in-hospital delay in stroke&#xD;
      by educating hospital personal, physicians, emergency medical services (EMS) and the public,&#xD;
      and by reorganizing stroke centres and EMS systems. Nevertheless, much time is still lost&#xD;
      before the patient arrives at the hospital. There are many causes for prehospital delay, but&#xD;
      most are related to patient-dependent factors and not system delay. Many stroke patients do&#xD;
      not recognize their own symptoms as signs of a stroke, do not understand the severity of&#xD;
      these symptoms and the importance of contacting EMS immediately. Besides, acute cognitive&#xD;
      impairment, aphasia and/or hemiplegia makes it difficult to call for medical assistance&#xD;
      without help from a bystander. Increased prehospital delay can also be caused by&#xD;
      inappropriate help-seeking behaviour, such as using a private vehicle, visiting a general&#xD;
      practitioner (GP) or having a wait-and-see attitude.&#xD;
&#xD;
      Half of the patients and bystanders choose not to contact the EMS, but call their GP or the&#xD;
      out-of-hours GP instead. Therefore, it is of great importance that persons working with&#xD;
      telephone triage in these health services (e.g. GPs) recognize stroke symptoms and&#xD;
      immediately refer the patient to a stroke centre. In a recent German study, GPs generally&#xD;
      perceived stroke and transient ischemic attack (TIA) as medical emergencies. However, when&#xD;
      using stroke case scenarios, only two thirds of the patients with clear stroke symptoms were&#xD;
      referred as a medical emergency.&#xD;
&#xD;
      Several studies have evaluated the effect of educational campaigns on stroke knowledge and&#xD;
      help-seeking behaviour. Many of the campaigns have successfully increased the awareness of&#xD;
      stroke symptoms in the public, but they have had little effect in improving the behavioural&#xD;
      response; this implies that the higher level of knowledge does not necessary result in&#xD;
      appropriate actions in the emergency situation. On the other hand, two recent studies found&#xD;
      an association between number of stroke symptoms correctly reported and the intention to call&#xD;
      an ambulance. Another study found that the ability to recall two core stroke symptoms (facial&#xD;
      weakness, limb weakness, or speech problems) was associated with seeking immediate ambulance&#xD;
      assistance. The few studies that have examined the effect of stroke educational campaigns on&#xD;
      revascularization therapies and reduced symptom to admission times have had inconsistent&#xD;
      findings. If future stroke campaigns are to have an impact on the number of patients&#xD;
      presenting within the reperfusion time window, it is of great importance to have a detailed&#xD;
      knowledge of the reasons for prehospital delay.&#xD;
&#xD;
      To our experience, no former studies have systematically collected detailed information about&#xD;
      stroke knowledge in patients and bystanders and combined these data with a complete&#xD;
      time-and-event mapping of the prehospital phase for all patients.&#xD;
&#xD;
      Hypotheses&#xD;
&#xD;
        1. Prehospital delay in stroke treatment is mainly caused by:&#xD;
&#xD;
             1. Patient delay: patients and/or bystanders who do not recognize stroke symptoms as&#xD;
                signs of severe illness that require immediate contact to the emergency medical&#xD;
                services (EMS).&#xD;
&#xD;
             2. System delay: low accuracy in telephone triage and the diagnostic process.&#xD;
&#xD;
        2. National multimedia stroke campaigns can improve the general knowledge of stroke, ensure&#xD;
           expedient help-seeking behaviour and increase the number of patients calling EMS&#xD;
           directly.&#xD;
&#xD;
      Research plan&#xD;
&#xD;
      Study 1: Characterization of stroke symptom knowledge, help-seeking behaviour and prehospital&#xD;
      delay in a cohort of consecutive stroke patients and their bystanders (cross sectional&#xD;
      descriptive study).&#xD;
&#xD;
      Aims:&#xD;
&#xD;
        1. To explore the knowledge of stroke in stroke patients and their bystanders.&#xD;
&#xD;
        2. To explore the process from onset of symptoms until admission to hospital (including&#xD;
           contact to EMS and/or GP/out-of-hours GP) and the reasons for prehospital delay.&#xD;
&#xD;
        3. To explore the association between stroke knowledge, help-seeking behaviour and&#xD;
           receiving revascularization therapy.&#xD;
&#xD;
           Primary objectives:&#xD;
&#xD;
           To determine:&#xD;
&#xD;
             -  The proportion of stroke patients/bystanders knowing at least two core symptoms of&#xD;
                stroke (defined as facial palsy, palsy of extremities and aphasia/dysarthria).&#xD;
&#xD;
             -  The proportion of stroke patients/bystanders making a direct EMS call.&#xD;
&#xD;
           Secondary objectives:&#xD;
&#xD;
           To determine:&#xD;
&#xD;
             -  The proportion of stroke patients/bystanders contacting their GP or out-of-hours GP&#xD;
                in first line.&#xD;
&#xD;
             -  The proportion of patients contacting a family member or friend in first line.&#xD;
&#xD;
             -  The average number of stroke symptoms each patient/bystander can identify.&#xD;
&#xD;
             -  The proportion of patients arriving at hospital within 3 hours of symptom onset&#xD;
                overall and stratified by whether the patients made a direct EMS call or had&#xD;
                knowledge of at least to core stroke symptoms.&#xD;
&#xD;
             -  The proportion of patients receiving revascularization therapy overall and&#xD;
                stratified by whether the patients made a direct EMS call or had knowledge of at&#xD;
                least to core stroke symptoms.&#xD;
&#xD;
             -  Whether stroke characteristics (stroke severity, type of stroke, stroke&#xD;
                lateralization), medical history with earlier stroke and/or socioeconomic status&#xD;
                are associated with prehospital delay.&#xD;
&#xD;
           Method:&#xD;
&#xD;
           Based on detailed pilot interviews with 30 consecutive stroke patients from The&#xD;
           Department of Neurology at Aarhus University Hospital, the investigators developed a&#xD;
           structured interview assessing the knowledge in both the patient and the bystander of&#xD;
           stroke risk factors, symptoms of stroke and their help-seeking behaviour.&#xD;
&#xD;
           The interview will be combined with background demographic characteristics and clinical&#xD;
           information. The investigators will use the patient's medical record (EPJ) and the&#xD;
           Danish Stroke Register (DSR) to complete this form. Registration of the patient's route&#xD;
           from onset of symptoms to admission to stroke centre will provide us with a complete&#xD;
           overview of the timeline.&#xD;
&#xD;
           For patients arriving by ambulance, the investigators will use the prehospital patient&#xD;
           journal (PPJ) to document the different phases of prehospital delay. For patients who&#xD;
           have been in contact with their GP, the GP will receive an electronic questionnaire to&#xD;
           explore the time- and event pathway from first contact until admitting the patient to&#xD;
           hospital, alternatively encouraging the patient/ bystander to contact EMS. The GPs will&#xD;
           be remunerated for returning a completed questionnaire, and the investigators expect a&#xD;
           response rate of 80%. For patients who have been in contact with the out of-hours GP,&#xD;
           the investigators will use the out of-hours medical record. Number of contacts to GP,&#xD;
           out-of-hours GP or EMS will be registered.&#xD;
&#xD;
           Selection of patients and bystanders:&#xD;
&#xD;
           All consecutive patients (and bystanders) with AIS, transient ischemic attack (TIA) and&#xD;
           intracerebral haemorrhage (ICH) admitted to the Department of Neurology and the vascular&#xD;
           out-patient clinic at Aarhus University Hospital and Regional Hospital West Jutland&#xD;
           (Holstebro) in the period 28 January 2018 - 10 May 2018 will be interviewed.&#xD;
&#xD;
           The investigators expect a total of 500 eligible patients and 300 bystanders included&#xD;
           during the 3-month period. Patients will be interviewed during the acute in-hospital&#xD;
           stroke phase.&#xD;
&#xD;
           The bystander is defined as the person who was with the patient, or was called for by&#xD;
           the patient, when the patient got ill. This is usually a close relative, but can also be&#xD;
           a friend, college or a nurse in home-nursing. Every effort will be made to interview the&#xD;
           bystander, either in person or by telephone.&#xD;
&#xD;
           Inclusion /exclusion criteria: see other section&#xD;
&#xD;
           Interview:&#xD;
&#xD;
           The structured interviews will be performed by trained research nurses or a research&#xD;
           physician from the Department of Neurology, Aarhus University Hospital (AUH), or&#xD;
           Regional Hospital West Jutland (Holstebro).&#xD;
&#xD;
           Study 2: Stroke awareness and help-seeking behaviour before and 6 months after&#xD;
           initiation of a national stroke awareness campaign.&#xD;
&#xD;
           Aim: To evaluate the immediate effect of the national campaign six months after&#xD;
           initiation.&#xD;
&#xD;
           Primary objectives:&#xD;
&#xD;
           To determine&#xD;
&#xD;
             -  Whether a stroke campaign has increased the proportion of stroke-patients and&#xD;
                bystanders making a primary EMS call.&#xD;
&#xD;
             -  Whether a stroke campaign has increased the proportion of stroke patients,&#xD;
                bystanders and patients with risk factors of stroke, knowing at least two core&#xD;
                symptoms of stroke.&#xD;
&#xD;
           Secondary objectives:&#xD;
&#xD;
           Objectives from study 1&#xD;
&#xD;
           Method:&#xD;
&#xD;
           The national stroke awareness campaign is planned to run in 2019 and 2020 and is&#xD;
           organized through the network of Danish Council for Resuscitation in collaboration with&#xD;
           TrygFonden. The TrygFonden supports projects that contribute to better health and safety&#xD;
           in the Danish population; from first aid courses to research projects. Coinciding this&#xD;
           campaign Danish Regions have taken initiative to a nationwide networking between the&#xD;
           pre-hospital organization and acute stroke hospitals in order to increase stroke&#xD;
           identification by EMS and paramedics and reduce prehospital time-delays.&#xD;
&#xD;
           This initiative has started in 2017 and will run through 2018 and several years. The&#xD;
           stroke awareness campaign will therefore run in an optimal situation of collaboration&#xD;
           between stroke health care professionals and public service.&#xD;
&#xD;
           The investigators will evaluate the effect of the campaign and optimization of the&#xD;
           prehospital service by comparing the results from study 1 described above and will&#xD;
           conduct a similar study in 2020 when the campaign has been running for six months.&#xD;
&#xD;
           Methodological considerations&#xD;
&#xD;
           Sample size calculation:&#xD;
&#xD;
           Study 1 (and 2):&#xD;
&#xD;
           The sample size calculation is based on data from the pilot study examining stroke&#xD;
           knowledge and help seeking behavior in patients with acute stroke. The proportion of&#xD;
           stroke patients (bystanders) who made a direct call to EMS was 40%. To detect a 15 %&#xD;
           absolute increase in in patients/bystanders making a direct EMS call after a national&#xD;
           stroke campaign, at a power of 80% and a significance level of 5%, a sample size of at&#xD;
           least 346 will be required. To account for patients with pre-stroke modified Rankin&#xD;
           Scale (mRS) ≥ 3, patients who cannot be reached and patients/bystanders not willing to&#xD;
           participate the investigators therefore plan to include 500 patients and 300 bystanders.&#xD;
&#xD;
           Planned statistical analyses:&#xD;
&#xD;
           Cohort characteristics are summarized using percentages or medians and interquartile&#xD;
           range (Q1-Q3) as appropriate. Data with non-normal distributions and/or with unequal&#xD;
           variance are compared using the Mann-Whitney U-test. In addition, comparisons will be&#xD;
           made using multivariable linear and binary regression with adjustment for potential&#xD;
           confounding factors.&#xD;
&#xD;
           Data handling and records:&#xD;
&#xD;
           All study data will be recorded in an electronic Case Report Form (REDCap) with&#xD;
           identification via a study identification number. The study will be governed by the&#xD;
           rules and regulations laid down in the Danish Act on Processing of Personal Data.&#xD;
           Approval is obtained from the Danish Data Protection Agency. No personal data will be&#xD;
           shared with any foreign countries.&#xD;
&#xD;
           Patient participation will be recorded in the medical record. Data will be deleted after&#xD;
           15 years.&#xD;
&#xD;
           Feasibility The PhD-fellow, M.D. Ane Bull Iversen (ABI) will be part of &quot;acute&#xD;
           conditions&quot; - group led by Senior researcher, GP, PhD Morten Bondo Christensen at the&#xD;
           Research Unit for General Practice, Department of Public Health, Aarhus University,&#xD;
           where also the main supervisor Professor, GP, PhD Bo Christensen is employed. The group&#xD;
           and the academic environment possess the required expertise in general practice&#xD;
           medicine, epidemiology, data management and biostatistics to fully support this project&#xD;
           during the entire PhD programme.&#xD;
&#xD;
           ABI will be employed at the Department of Neurology, Aarhus University Hospital, where&#xD;
           co-supervisor Grethe Andersen is professor and head of the Danish Stroke Center.&#xD;
           Co-supervisor Søren Paaske Johnsen is professor at the Department of Clinical Medicine,&#xD;
           Aalborg University and Aalborg University Hospital.&#xD;
&#xD;
           ABI will be responsible for the development and the execution of the structured&#xD;
           interviews and questionnaires and cooperation with other departments. She will also be&#xD;
           responsible for the data collection and the data analysis. In addition to writing her&#xD;
           PhD thesis, she will also be responsible for writing the first drafts and the final&#xD;
           versions of all papers.&#xD;
&#xD;
           ABI is a medical doctor in residency for general practice. She has obtained clinical&#xD;
           experience with general practice through 18 months of specialty training in general&#xD;
           medicine.&#xD;
&#xD;
           Ethics and approvals Approval is obtained from the Danish Data Protection Agency and the&#xD;
           Multipractice Study Committee of the Danish College of General Practitioners. Approval&#xD;
           from The Central Denmark Region Committees on Health Research Ethics is not necessary.&#xD;
&#xD;
           Economy A grant from TrygFonden will cover most of the salary for the PhD-fellow and for&#xD;
           part-time research nurses during the three-year period. The research group has received&#xD;
           a grant from the Committee for Quality Improvement and Continuing Medical Education in&#xD;
           general practice in the Central Denmark Regions and the Multipractice Study Committee of&#xD;
           the Danish College of General Practitioners. (The latest to compensate participating GPs&#xD;
           for answering the questionnaire).&#xD;
&#xD;
           Publication policy The results of the study, both negative, inconclusive and positive,&#xD;
           will be disseminated as widely as possible. This will take place through publication of&#xD;
           scientific papers in international peer-reviewed journals, conference presentations and&#xD;
           press releases (if relevant).&#xD;
&#xD;
           Perspectives This study will provide new information about stroke patients, bystanders&#xD;
           and persons at high risk of getting a stroke, their knowledge on stroke and their&#xD;
           help-seeking behaviour. If more knowledge about the factors that cause prehospital delay&#xD;
           in stroke treatment are obtained, the investigators will also know which areas to focus&#xD;
           on in the future to improve the outcome for stroke patients.&#xD;
&#xD;
           Part of this project will examine the effect of TrygFondens national stroke campaign,&#xD;
           which is expected to have impact on general knowledge and help-seeking behaviour. If&#xD;
           more people know about the core symptoms of stroke, more people will also know how to&#xD;
           react to these symptoms by calling EMS which will eventually increase reperfusion&#xD;
           therapy rates. This is expected to considerably improve stroke morbidity and mortality&#xD;
           and to reduce both the individual suffering and the societal costs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 28, 2018</start_date>
  <completion_date type="Actual">December 29, 2020</completion_date>
  <primary_completion_date type="Actual">May 10, 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>The proportion of stroke patients/bystanders knowing at least two core symptoms of stroke (defined as facial palsy, palsy of extremities and aphasia/dysarthria).</measure>
    <time_frame>Study period: 01/28/18 - 12/31/20</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>The proportion of stroke patients/bystanders making a direct EMS call.</measure>
    <time_frame>Study period: 01/28/18 - 12/31/20</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>The proportion of stroke patients/bystanders contacting their GP or out-of-hours GP in first line.</measure>
    <time_frame>Study period: 01/28/18 - 12/31/20</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients contacting a family member or friend in first line.</measure>
    <time_frame>Study period: 01/28/18 - 12/31/20</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The average number of stroke symptoms each patient/bystander can identify.</measure>
    <time_frame>Study period: 01/28/18 - 12/31/20</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients arriving at hospital within 3 hours of symptom onset overall and stratified by whether the patients made a direct EMS call or had knowledge of at least to core stroke symptoms.</measure>
    <time_frame>Study period: 01/28/18 - 12/31/20</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients receiving revascularization therapy overall and stratified by whether the patients made a direct EMS call or had knowledge of at least to core stroke symptoms.</measure>
    <time_frame>Study period: 01/28/18 - 12/31/20</time_frame>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">650</enrollment>
  <condition>Stroke</condition>
  <arm_group>
    <arm_group_label>Stroke patients</arm_group_label>
    <description>Structured interviews of patients with stroke, admitted at the Department of Neurology, Aarhus University hospital and Regional Hospital West Jutland (Holstebro)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Bystander</arm_group_label>
    <description>Structured interviews of bystanders of patients with stroke, admitted at the Department of Neurology, Aarhus University hospital and Regional Hospital West Jutland (Holstebro)</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Structured interview</intervention_name>
    <description>Interview contains questions about stroke knowledge and help-seeking behaviour on the day the stroke occured.</description>
    <arm_group_label>Bystander</arm_group_label>
    <arm_group_label>Stroke patients</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        All consecutive patients (and bystanders) with AIS, transient ischemic attack (TIA) and&#xD;
        intracerebral haemorrhage (ICH) admitted to the Department of Neurology and the vascular&#xD;
        out-patient clinic at Aarhus University Hospital and Regional Hospital West Jutland&#xD;
        (Holstebro) in the two study periodes.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosed with AIS, TIA or ICH&#xD;
&#xD;
          -  Admitted to the Department of Neurology at Aarhus University Hospital or Regional&#xD;
             Hospital West Jutland (Holstebro)&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Onset of symptoms ≤ 7 days before time of interview&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Modified Rankin Scale (mRS) ≥ 3* (pre-stroke)&#xD;
&#xD;
          -  Transferred from other regions in Denmark or abroad&#xD;
&#xD;
          -  Not willing to participate in the study&#xD;
&#xD;
          -  Cannot be reached (&quot;out of office&quot;)&#xD;
&#xD;
          -  Non-Danish speaking&#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>Grethe Andersen, DMSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor, DMSc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Aarhus University Hospital</name>
      <address>
        <city>Aarhus</city>
        <zip>8000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Unit for General Practice</name>
      <address>
        <city>Aarhus</city>
        <zip>8000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
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  <verification_date>April 2021</verification_date>
  <study_first_submitted>November 22, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 30, 2018</study_first_posted>
  <last_update_submitted>April 27, 2021</last_update_submitted>
  <last_update_submitted_qc>April 27, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>prehospital delay</keyword>
  <keyword>help-seeking behaviour</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</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/NCT03759691
org study id: 030683
nct id: NCT03759691
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Stroke is the second-leading cause of death worldwide and a leading cause of long-term
      disability. Annually 12,000 people in Denmark suffers a stroke; half of them will have
      long-term disabilities that may affect the activities of daily living. In addition to
      substantial individual suffering, stroke is also associated with considerable costs to
      society. Acute reperfusion therapies started within 4.5 to 6 hours (in some up to 24 hours)
      from symptom onset for acute ischaemic stroke (AIS) have revolutionized the acute stroke
      treatment and considerably improved the overall prognosis and mortality. However, only 15-25%
      of Danish patients are eligible to acute treatment. Numerous attempts to reduce both
      prehospital and in-hospital delay in stroke have been made, but much time is still lost in
      the prehospital phase.

      Many stroke patients do not recognize their own symptoms as signs of a stroke or do not
      understand the importance of calling Emergecy Medical Services (EMS) immediately. Others
      cannot call for help unless they have a bystander, because of cognitive impairment or
      aphasia. Some patients have a wait-and-see attitude, contact their GP or out-of-hours GP,
      which also can increase the delay. Educational stroke campaigns can increase knowledge,
      improve help-seeking behaviour and increase the number of patients eligible for reperfusion
      therapies. The foundation TrygFonden is planning a national stroke campaign in 2019.

      Aims:

        1. To explore the knowledge of stroke in stroke patients and bystanders.

        2. To explore the process from onset of symptoms until admission to hospital and the
           reasons for prehospital delay.

        3. To explore the association between stroke knowledge, help-seeking behaviour and
           receiving revascularization therapy.

        4. To evaluate the immediate effect of the national campaign six months after initiation.

      Material and methods:

      Study 1:

      Structured interviews of stroke patients (and bystanders) admitted to the Department of
      Neurology at Aarhus University Hospital and Regional Hospital West Jutland (Holstebro). The
      investigators will use the patient's medical record (EPJ) and the Danish Stroke Register
      (DSR) and map the patient's route from onset of symptoms to admission to stroke centre,
      including contact to general practitioner (GP), out-of-hours GP or Emergency Medical Services
      (EMS). For patients who have been in contact with their GP, the GP will receive an electronic
      questionnaire to explore the time- and event pathway from first contact until admitting the
      patient to hospital. The investigators will interview 500 patients and approximately 300
      bystanders over a period of 3 months.

      Study 2:

      The investigators will evaluate the effect of the national stroke campaign by conducting a
      similar study in 2020 when the campaign has been running for six months.

      Perspectives:

      This study will provide new information about stroke patients and bystanders, their knowledge
      of stroke and their help-seeking behaviour. If more knowledge about the factors that cause
      prehospital delay in stroke treatment are obtained, the investigators will know which areas
      to focus on in the future to improve the outcome for stroke patients. Part of this project
      will examine the effect of TrygFondens national stroke campaign, which is expected to have
      impact on general knowledge and help-seeking behaviour. If more people know the core symptoms
      of stroke, hopefully more people will also know how to react to these symptoms by calling
      EMS. This will eventually increase reperfusion therapy rates, considerably improve stroke
      morbidity and mortality and reduce both individual suffering and the societal costs.
Stroke awareness and help-seeking behaviour: predictors for prehospital delay in stroke
      treatment

      Ane Bull Iversen, MD Section for General Medical Practice Department of Public Health and
      Department of Neurology Department of Clinical Medicine Aarhus University

      Supervisors:

      Professor Bo Christensen, PhD, MD Section for General Medical Practice Department of Public
      Health Aarhus University

      Professor Grethe Andersen, PhD, MD Department of Neurology Department of Clinical Medicine
      Aarhus University

      Senior researcher Morten Bondo Christensen, PhD, MD Research Unit for General Practice
      Department of Public Health Aarhus University

      Professor Søren Paaske Johnsen, PhD, MD Center for Clinical Health Services Research
      Department of Clinical Medicine Aalborg University and Aalborg University Hospital

      Background Stroke is the second-leading cause of death worldwide and a leading cause of
      long-term disability. Each year 12,000 people in Denmark are hit by a stroke. In addition to
      substantial individual suffering, stroke is also associated with considerable costs to
      society.

      The World Health Organization (WHO) has estimated a marked increase in the stroke prevalence
      in 2025 as a result of ageing populations. This development will increase the need to
      identify areas with potential for improvement in the treatment of stroke. Acute reperfusion
      therapies started within 4.5 to 6 hours (in some up to 24 hours) from symptom onset for AIS
      have revolutionized the acute stroke treatment and considerably improved the overall
      prognosis and mortality. However, only 15-25% of Danish patients are eligible to acute
      treatment. This is primarily due to presentation outside the time window for intravenous
      thrombolysis and endo¬vascular treatment at the stroke centre. Time is also of utmost
      importance in patients receiving reperfusions therapies, as the chance of functional
      independence decreases rapidly during the first few hours after stroke onset.

      Numerous attempts have been made to reduce both prehospital and in-hospital delay in stroke
      by educating hospital personal, physicians, emergency medical services (EMS) and the public,
      and by reorganizing stroke centres and EMS systems. Nevertheless, much time is still lost
      before the patient arrives at the hospital. There are many causes for prehospital delay, but
      most are related to patient-dependent factors and not system delay. Many stroke patients do
      not recognize their own symptoms as signs of a stroke, do not understand the severity of
      these symptoms and the importance of contacting EMS immediately. Besides, acute cognitive
      impairment, aphasia and/or hemiplegia makes it difficult to call for medical assistance
      without help from a bystander. Increased prehospital delay can also be caused by
      inappropriate help-seeking behaviour, such as using a private vehicle, visiting a general
      practitioner (GP) or having a wait-and-see attitude.

      Half of the patients and bystanders choose not to contact the EMS, but call their GP or the
      out-of-hours GP instead. Therefore, it is of great importance that persons working with
      telephone triage in these health services (e.g. GPs) recognize stroke symptoms and
      immediately refer the patient to a stroke centre. In a recent German study, GPs generally
      perceived stroke and transient ischemic attack (TIA) as medical emergencies. However, when
      using stroke case scenarios, only two thirds of the patients with clear stroke symptoms were
      referred as a medical emergency.

      Several studies have evaluated the effect of educational campaigns on stroke knowledge and
      help-seeking behaviour. Many of the campaigns have successfully increased the awareness of
      stroke symptoms in the public, but they have had little effect in improving the behavioural
      response; this implies that the higher level of knowledge does not necessary result in
      appropriate actions in the emergency situation. On the other hand, two recent studies found
      an association between number of stroke symptoms correctly reported and the intention to call
      an ambulance. Another study found that the ability to recall two core stroke symptoms (facial
      weakness, limb weakness, or speech problems) was associated with seeking immediate ambulance
      assistance. The few studies that have examined the effect of stroke educational campaigns on
      revascularization therapies and reduced symptom to admission times have had inconsistent
      findings. If future stroke campaigns are to have an impact on the number of patients
      presenting within the reperfusion time window, it is of great importance to have a detailed
      knowledge of the reasons for prehospital delay.

      To our experience, no former studies have systematically collected detailed information about
      stroke knowledge in patients and bystanders and combined these data with a complete
      time-and-event mapping of the prehospital phase for all patients.

      Hypotheses

        1. Prehospital delay in stroke treatment is mainly caused by:

             1. Patient delay: patients and/or bystanders who do not recognize stroke symptoms as
                signs of severe illness that require immediate contact to the emergency medical
                services (EMS).

             2. System delay: low accuracy in telephone triage and the diagnostic process.

        2. National multimedia stroke campaigns can improve the general knowledge of stroke, ensure
           expedient help-seeking behaviour and increase the number of patients calling EMS
           directly.

      Research plan

      Study 1: Characterization of stroke symptom knowledge, help-seeking behaviour and prehospital
      delay in a cohort of consecutive stroke patients and their bystanders (cross sectional
      descriptive study).

      Aims:

        1. To explore the knowledge of stroke in stroke patients and their bystanders.

        2. To explore the process from onset of symptoms until admission to hospital (including
           contact to EMS and/or GP/out-of-hours GP) and the reasons for prehospital delay.

        3. To explore the association between stroke knowledge, help-seeking behaviour and
           receiving revascularization therapy.

           Primary objectives:

           To determine:

             -  The proportion of stroke patients/bystanders knowing at least two core symptoms of
                stroke (defined as facial palsy, palsy of extremities and aphasia/dysarthria).

             -  The proportion of stroke patients/bystanders making a direct EMS call.

           Secondary objectives:

           To determine:

             -  The proportion of stroke patients/bystanders contacting their GP or out-of-hours GP
                in first line.

             -  The proportion of patients contacting a family member or friend in first line.

             -  The average number of stroke symptoms each patient/bystander can identify.

             -  The proportion of patients arriving at hospital within 3 hours of symptom onset
                overall and stratified by whether the patients made a direct EMS call or had
                knowledge of at least to core stroke symptoms.

             -  The proportion of patients receiving revascularization therapy overall and
                stratified by whether the patients made a direct EMS call or had knowledge of at
                least to core stroke symptoms.

             -  Whether stroke characteristics (stroke severity, type of stroke, stroke
                lateralization), medical history with earlier stroke and/or socioeconomic status
                are associated with prehospital delay.

           Method:

           Based on detailed pilot interviews with 30 consecutive stroke patients from The
           Department of Neurology at Aarhus University Hospital, the investigators developed a
           structured interview assessing the knowledge in both the patient and the bystander of
           stroke risk factors, symptoms of stroke and their help-seeking behaviour.

           The interview will be combined with background demographic characteristics and clinical
           information. The investigators will use the patient's medical record (EPJ) and the
           Danish Stroke Register (DSR) to complete this form. Registration of the patient's route
           from onset of symptoms to admission to stroke centre will provide us with a complete
           overview of the timeline.

           For patients arriving by ambulance, the investigators will use the prehospital patient
           journal (PPJ) to document the different phases of prehospital delay. For patients who
           have been in contact with their GP, the GP will receive an electronic questionnaire to
           explore the time- and event pathway from first contact until admitting the patient to
           hospital, alternatively encouraging the patient/ bystander to contact EMS. The GPs will
           be remunerated for returning a completed questionnaire, and the investigators expect a
           response rate of 80%. For patients who have been in contact with the out of-hours GP,
           the investigators will use the out of-hours medical record. Number of contacts to GP,
           out-of-hours GP or EMS will be registered.

           Selection of patients and bystanders:

           All consecutive patients (and bystanders) with AIS, transient ischemic attack (TIA) and
           intracerebral haemorrhage (ICH) admitted to the Department of Neurology and the vascular
           out-patient clinic at Aarhus University Hospital and Regional Hospital West Jutland
           (Holstebro) in the period 28 January 2018 - 10 May 2018 will be interviewed.

           The investigators expect a total of 500 eligible patients and 300 bystanders included
           during the 3-month period. Patients will be interviewed during the acute in-hospital
           stroke phase.

           The bystander is defined as the person who was with the patient, or was called for by
           the patient, when the patient got ill. This is usually a close relative, but can also be
           a friend, college or a nurse in home-nursing. Every effort will be made to interview the
           bystander, either in person or by telephone.

           Inclusion /exclusion criteria: see other section

           Interview:

           The structured interviews will be performed by trained research nurses or a research
           physician from the Department of Neurology, Aarhus University Hospital (AUH), or
           Regional Hospital West Jutland (Holstebro).

           Study 2: Stroke awareness and help-seeking behaviour before and 6 months after
           initiation of a national stroke awareness campaign.

           Aim: To evaluate the immediate effect of the national campaign six months after
           initiation.

           Primary objectives:

           To determine

             -  Whether a stroke campaign has increased the proportion of stroke-patients and
                bystanders making a primary EMS call.

             -  Whether a stroke campaign has increased the proportion of stroke patients,
                bystanders and patients with risk factors of stroke, knowing at least two core
                symptoms of stroke.

           Secondary objectives:

           Objectives from study 1

           Method:

           The national stroke awareness campaign is planned to run in 2019 and 2020 and is
           organized through the network of Danish Council for Resuscitation in collaboration with
           TrygFonden. The TrygFonden supports projects that contribute to better health and safety
           in the Danish population; from first aid courses to research projects. Coinciding this
           campaign Danish Regions have taken initiative to a nationwide networking between the
           pre-hospital organization and acute stroke hospitals in order to increase stroke
           identification by EMS and paramedics and reduce prehospital time-delays.

           This initiative has started in 2017 and will run through 2018 and several years. The
           stroke awareness campaign will therefore run in an optimal situation of collaboration
           between stroke health care professionals and public service.

           The investigators will evaluate the effect of the campaign and optimization of the
           prehospital service by comparing the results from study 1 described above and will
           conduct a similar study in 2020 when the campaign has been running for six months.

           Methodological considerations

           Sample size calculation:

           Study 1 (and 2):

           The sample size calculation is based on data from the pilot study examining stroke
           knowledge and help seeking behavior in patients with acute stroke. The proportion of
           stroke patients (bystanders) who made a direct call to EMS was 40%. To detect a 15 %
           absolute increase in in patients/bystanders making a direct EMS call after a national
           stroke campaign, at a power of 80% and a significance level of 5%, a sample size of at
           least 346 will be required. To account for patients with pre-stroke modified Rankin
           Scale (mRS) ≥ 3, patients who cannot be reached and patients/bystanders not willing to
           participate the investigators therefore plan to include 500 patients and 300 bystanders.

           Planned statistical analyses:

           Cohort characteristics are summarized using percentages or medians and interquartile
           range (Q1-Q3) as appropriate. Data with non-normal distributions and/or with unequal
           variance are compared using the Mann-Whitney U-test. In addition, comparisons will be
           made using multivariable linear and binary regression with adjustment for potential
           confounding factors.

           Data handling and records:

           All study data will be recorded in an electronic Case Report Form (REDCap) with
           identification via a study identification number. The study will be governed by the
           rules and regulations laid down in the Danish Act on Processing of Personal Data.
           Approval is obtained from the Danish Data Protection Agency. No personal data will be
           shared with any foreign countries.

           Patient participation will be recorded in the medical record. Data will be deleted after
           15 years.

           Feasibility The PhD-fellow, M.D. Ane Bull Iversen (ABI) will be part of "acute
           conditions" - group led by Senior researcher, GP, PhD Morten Bondo Christensen at the
           Research Unit for General Practice, Department of Public Health, Aarhus University,
           where also the main supervisor Professor, GP, PhD Bo Christensen is employed. The group
           and the academic environment possess the required expertise in general practice
           medicine, epidemiology, data management and biostatistics to fully support this project
           during the entire PhD programme.

           ABI will be employed at the Department of Neurology, Aarhus University Hospital, where
           co-supervisor Grethe Andersen is professor and head of the Danish Stroke Center.
           Co-supervisor Søren Paaske Johnsen is professor at the Department of Clinical Medicine,
           Aalborg University and Aalborg University Hospital.

           ABI will be responsible for the development and the execution of the structured
           interviews and questionnaires and cooperation with other departments. She will also be
           responsible for the data collection and the data analysis. In addition to writing her
           PhD thesis, she will also be responsible for writing the first drafts and the final
           versions of all papers.

           ABI is a medical doctor in residency for general practice. She has obtained clinical
           experience with general practice through 18 months of specialty training in general
           medicine.

           Ethics and approvals Approval is obtained from the Danish Data Protection Agency and the
           Multipractice Study Committee of the Danish College of General Practitioners. Approval
           from The Central Denmark Region Committees on Health Research Ethics is not necessary.

           Economy A grant from TrygFonden will cover most of the salary for the PhD-fellow and for
           part-time research nurses during the three-year period. The research group has received
           a grant from the Committee for Quality Improvement and Continuing Medical Education in
           general practice in the Central Denmark Regions and the Multipractice Study Committee of
           the Danish College of General Practitioners. (The latest to compensate participating GPs
           for answering the questionnaire).

           Publication policy The results of the study, both negative, inconclusive and positive,
           will be disseminated as widely as possible. This will take place through publication of
           scientific papers in international peer-reviewed journals, conference presentations and
           press releases (if relevant).

           Perspectives This study will provide new information about stroke patients, bystanders
           and persons at high risk of getting a stroke, their knowledge on stroke and their
           help-seeking behaviour. If more knowledge about the factors that cause prehospital delay
           in stroke treatment are obtained, the investigators will also know which areas to focus
           on in the future to improve the outcome for stroke patients.

           Part of this project will examine the effect of TrygFondens national stroke campaign,
           which is expected to have impact on general knowledge and help-seeking behaviour. If
           more people know about the core symptoms of stroke, more people will also know how to
           react to these symptoms by calling EMS which will eventually increase reperfusion
           therapy rates. This is expected to considerably improve stroke morbidity and mortality
           and to reduce both the individual suffering and the societal costs.
observational model: Case-Only
time perspective: Cross-Sectional
measure: The proportion of stroke patients/bystanders knowing at least two core symptoms of stroke (defined as facial palsy, palsy of extremities and aphasia/dysarthria).
time frame: Study period: 01/28/18 - 12/31/20
measure: The proportion of stroke patients/bystanders making a direct EMS call.
time frame: Study period: 01/28/18 - 12/31/20
measure: The proportion of stroke patients/bystanders contacting their GP or out-of-hours GP in first line.
time frame: Study period: 01/28/18 - 12/31/20
measure: The proportion of patients contacting a family member or friend in first line.
time frame: Study period: 01/28/18 - 12/31/20
measure: The average number of stroke symptoms each patient/bystander can identify.
time frame: Study period: 01/28/18 - 12/31/20
measure: The proportion of patients arriving at hospital within 3 hours of symptom onset overall and stratified by whether the patients made a direct EMS call or had knowledge of at least to core stroke symptoms.
time frame: Study period: 01/28/18 - 12/31/20
measure: The proportion of patients receiving revascularization therapy overall and stratified by whether the patients made a direct EMS call or had knowledge of at least to core stroke symptoms.
time frame: Study period: 01/28/18 - 12/31/20
arm group label: Stroke patients
description: Structured interviews of patients with stroke, admitted at the Department of Neurology, Aarhus University hospital and Regional Hospital West Jutland (Holstebro)
arm group label: Bystander
description: Structured interviews of bystanders of patients with stroke, admitted at the Department of Neurology, Aarhus University hospital and Regional Hospital West Jutland (Holstebro)
intervention type: Behavioral
intervention name: Structured interview
description: Interview contains questions about stroke knowledge and help-seeking behaviour on the day the stroke occured.
arm group label: Bystander
arm group label: Stroke patients
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Grethe Andersen, DMSc
role: Principal Investigator
affiliation: Professor, DMSc
facility: 
facility: 
country: Denmark
url: http://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death
description: World Health Organization: The top 10 causes of death
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responsible party type: Sponsor
mesh term: Stroke
sharing ipd: No