<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/NCT03820999</url>
  </required_header>
  <id_info>
    <org_study_id>FCKPhDProject4</org_study_id>
    <nct_id>NCT03820999</nct_id>
  </id_info>
  <brief_title>An Intervention in a Primary Healthcare Setting to Reduce Lyme Neuroborreliosis Treatment Delay</brief_title>
  <acronym>NBdelay</acronym>
  <official_title>An Intervention in a Primary Healthcare Setting to Reduce Lyme Neuroborreliosis Treatment Delay</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Odense University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Odense University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This study evaluates the effect of written and oral information in a primary health care&#xD;
      setting on 1) patients referred to specialised examination for Lyme neuroborreliosis, 2)&#xD;
      delay from patient symptom debut to treatment for Lyme neuroborreliosis, and 3) number of&#xD;
      Borrelia serology tests from primary health care.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Lyme neuroborreliosis is among the most common neuroinfections in northern Europe. Residual&#xD;
      symptoms after treatment are a frequent problem in Lyme neuroborreliosis, and an association&#xD;
      between the delay from symptom debut to antibiotic treatment has been established. In a&#xD;
      previous study on Funen Island, Denmark, the delay from day of symptom debut to treatment for&#xD;
      Lyme neuroborreliosis patients was 24 days. This considerable treatment delay did not change&#xD;
      in the 20 years study period.&#xD;
&#xD;
      In the Danish health system, the general practitioners are the first medical professionals to&#xD;
      see the majority of patients. They can refer patients to the hospital for further examination&#xD;
      if indicated. Many general practitioners use Borrelia burgdorferi antibodies (igM/IgG) as a&#xD;
      screening tool when they suspect Lyme disease or see patients with uncharacteristic symptoms.&#xD;
      This is unfortunate, as the rash Erythema Migrans, the most common Borreliosis manifestation&#xD;
      in Europe, is a clinical diagnosis. Only around 50% of patients have positive antibodies at&#xD;
      time of Erythema Migrans diagnosis. Lyme neuroborreliosis is diagnosed based on symptoms and&#xD;
      the results from the cerebrospinal fluid, and cannot be diagnosed based on serology, which&#xD;
      only delays the time to diagnoses and treatment. The Danish guidelines on Lyme borreliosis&#xD;
      therefore discourage general practitioners from using Borrelia serology.&#xD;
&#xD;
      In the before mentioned study from Funen Island, several patients described multiple contacts&#xD;
      to their general practitioners, where the symptoms of Lyme neuroborreliosis were not&#xD;
      recognized. The cardinal symptom of radicular pain was associated with a longer delay than&#xD;
      many of the less common symptoms of Lyme neuroborreliosis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">February 2019</start_date>
  <completion_date type="Anticipated">April 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Open label interventional study where primary Health care Physicians in areas on Funen Island, Denmark, are included if they have their practice in an area with Lyme Neuroborreliosis incidens &gt; 4.6/100.000</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Open label study, due to the intervention (lectures) and the criteria for receiving the intervention (Lyme neuroborreliosis incidens &gt; 4.6/100.000), the study cannot be blinded.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of days from symptom debut to beginning of antibiotic treatment for Lyme neuroborreliosis</measure>
    <time_frame>0-90 days</time_frame>
    <description>Number of days from debut of neurological symptoms to beginning of antibiotic treatment for Lyme neuroborreliosis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of yearly referred Lyme patients</measure>
    <time_frame>Up to 4 years (1460 days).</time_frame>
    <description>Number of yearly referred patients in the two study arms in the two years before the intervention (2017+2018) and after the intervention (2019+2020).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Borrelia antibody tests in peripheral blood ordered by primary care physicians</measure>
    <time_frame>Up to 4 years (1460 days).</time_frame>
    <description>Number of Borrelia antibody tests in peripheral blood ordered by primary Health care physicians in the two study arms in the two years before (2017+2018) and after (2019 + 2020) the intervention.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Lyme Neuroborreliosis</condition>
  <arm_group>
    <arm_group_label>Teaching arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The Primary Health Care physicians getting oral and written information on tick-bites and Lyme disease with focus on Lyme neuroborreliosis.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Passive arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The Primary Health Care physicians that does not get contacted with an offer to receive oral and written information.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Oral and written information on tick-bites and Lyme disease</intervention_name>
    <description>See under study arm descriptions</description>
    <arm_group_label>Teaching arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Primary care physicians with a postal code in an area of Funen Island with a Lyme&#xD;
             neuroborreliosis incidens of &gt; 4.6/100.000&#xD;
&#xD;
          -  Patients with a postal address on Funen and a positive Borrelia intrathecal antibody&#xD;
             test (diagnostic for lyme neuroborreliosis) performed at the Department of Clinical&#xD;
             Microbiology, Odense University Hospital from January 1st 2017 - December 31st 2020&#xD;
&#xD;
          -  A Borrelia IgM/IgG serology ordered from Primary Health Care and performed at the&#xD;
             Department of Clinical Microbiology, Odense University Hospital from January 1st 2017&#xD;
             - December 31st 2020&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Primary care physicians with a postal code in an area of Funen Island with a Lyme&#xD;
             neuroborreliosis incidens of &lt; 4.7/100.000&#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>Fredrikke C Knudtzen, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Infectious Diseases, Odense University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Fredrikke C Knudtzen, MD</last_name>
    <phone>004529178083</phone>
    <email>fredrikke.christie.knudtzen@rsyd.dk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sigurdur Skarphédinsson, MD, PhD</last_name>
    <phone>004565414280</phone>
    <email>s.skarphedinsson@rsyd.dk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Clinical Center for Emerging and Vectorborne Infections</name>
      <address>
        <city>Odense</city>
        <state>Funen</state>
        <zip>5000</zip>
        <country>Denmark</country>
      </address>
    </facility>
    <contact>
      <last_name>Sigurdur Skarphedinsson, MD, PhD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <results_reference>
    <citation>Knudtzen FC, Andersen NS, Jensen TG, Skarphedinsson S. Characteristics and Clinical Outcome of Lyme Neuroborreliosis in a High Endemic Area, 1995-2014: A Retrospective Cohort Study in Denmark. Clin Infect Dis. 2017 Oct 16;65(9):1489-1495. doi: 10.1093/cid/cix568.</citation>
    <PMID>29048514</PMID>
  </results_reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 22, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>January 29, 2019</last_update_submitted>
  <last_update_submitted_qc>January 29, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 31, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Odense University Hospital</investigator_affiliation>
    <investigator_full_name>Fredrikke Christie Knudtzen</investigator_full_name>
    <investigator_title>Speciality Registrar, Specialist in Infectious Diseases, Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>treatment delay</keyword>
  <keyword>primary health care</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lyme Neuroborreliosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Due to Denmark´s strict data-sharing Laws, data will not be shared after completion of study.</ipd_description>
  </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/NCT03820999
org study id: FCKPhDProject4
nct id: NCT03820999
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study evaluates the effect of written and oral information in a primary health care
      setting on 1) patients referred to specialised examination for Lyme neuroborreliosis, 2)
      delay from patient symptom debut to treatment for Lyme neuroborreliosis, and 3) number of
      Borrelia serology tests from primary health care.
Lyme neuroborreliosis is among the most common neuroinfections in northern Europe. Residual
      symptoms after treatment are a frequent problem in Lyme neuroborreliosis, and an association
      between the delay from symptom debut to antibiotic treatment has been established. In a
      previous study on Funen Island, Denmark, the delay from day of symptom debut to treatment for
      Lyme neuroborreliosis patients was 24 days. This considerable treatment delay did not change
      in the 20 years study period.

      In the Danish health system, the general practitioners are the first medical professionals to
      see the majority of patients. They can refer patients to the hospital for further examination
      if indicated. Many general practitioners use Borrelia burgdorferi antibodies (igM/IgG) as a
      screening tool when they suspect Lyme disease or see patients with uncharacteristic symptoms.
      This is unfortunate, as the rash Erythema Migrans, the most common Borreliosis manifestation
      in Europe, is a clinical diagnosis. Only around 50% of patients have positive antibodies at
      time of Erythema Migrans diagnosis. Lyme neuroborreliosis is diagnosed based on symptoms and
      the results from the cerebrospinal fluid, and cannot be diagnosed based on serology, which
      only delays the time to diagnoses and treatment. The Danish guidelines on Lyme borreliosis
      therefore discourage general practitioners from using Borrelia serology.

      In the before mentioned study from Funen Island, several patients described multiple contacts
      to their general practitioners, where the symptoms of Lyme neuroborreliosis were not
      recognized. The cardinal symptom of radicular pain was associated with a longer delay than
      many of the less common symptoms of Lyme neuroborreliosis.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Open label interventional study where primary Health care Physicians in areas on Funen Island, Denmark, are included if they have their practice in an area with Lyme Neuroborreliosis incidens > 4.6/100.000
primary purpose: Treatment
masking: None (Open Label)
masking description: Open label study, due to the intervention (lectures) and the criteria for receiving the intervention (Lyme neuroborreliosis incidens > 4.6/100.000), the study cannot be blinded.
measure: Number of days from symptom debut to beginning of antibiotic treatment for Lyme neuroborreliosis
time frame: 0-90 days
description: Number of days from debut of neurological symptoms to beginning of antibiotic treatment for Lyme neuroborreliosis.
measure: Number of yearly referred Lyme patients
time frame: Up to 4 years (1460 days).
description: Number of yearly referred patients in the two study arms in the two years before the intervention (2017+2018) and after the intervention (2019+2020).
measure: Number of Borrelia antibody tests in peripheral blood ordered by primary care physicians
time frame: Up to 4 years (1460 days).
description: Number of Borrelia antibody tests in peripheral blood ordered by primary Health care physicians in the two study arms in the two years before (2017+2018) and after (2019 + 2020) the intervention.
arm group label: Teaching arm
arm group type: Experimental
description: The Primary Health Care physicians getting oral and written information on tick-bites and Lyme disease with focus on Lyme neuroborreliosis.
arm group label: Passive arm
arm group type: No Intervention
description: The Primary Health Care physicians that does not get contacted with an offer to receive oral and written information.
intervention type: Other
intervention name: Oral and written information on tick-bites and Lyme disease
description: See under study arm descriptions
arm group label: Teaching arm
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Fredrikke C Knudtzen, MD
role: Principal Investigator
affiliation: Department of Infectious Diseases, Odense University Hospital
last name: Fredrikke C Knudtzen, MD
phone: 004529178083
email: fredrikke.christie.knudtzen@rsyd.dk
last name: Sigurdur Skarphédinsson, MD, PhD
phone: 004565414280
email: s.skarphedinsson@rsyd.dk
facility: 
contact: 
country: Denmark
citation: Knudtzen FC, Andersen NS, Jensen TG, Skarphedinsson S. Characteristics and Clinical Outcome of Lyme Neuroborreliosis in a High Endemic Area, 1995-2014: A Retrospective Cohort Study in Denmark. Clin Infect Dis. 2017 Oct 16;65(9):1489-1495. doi: 10.1093/cid/cix568.
PMID: 29048514
responsible party type: Principal Investigator
investigator affiliation: Odense University Hospital
investigator full name: Fredrikke Christie Knudtzen
investigator title: Speciality Registrar, Specialist in Infectious Diseases, Principal Investigator
mesh term: Lyme Neuroborreliosis
sharing ipd: No
ipd description: Due to Denmark´s strict data-sharing Laws, data will not be shared after completion of study.