<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/NCT03789422</url>
  </required_header>
  <id_info>
    <org_study_id>TACUS- 38RC18.103</org_study_id>
    <nct_id>NCT03789422</nct_id>
  </id_info>
  <brief_title>Tranexamic Acid and Spontaneous Chronic Urticaria</brief_title>
  <acronym>TACUS</acronym>
  <official_title>Efficacy and Safety of Levocetirizine Alone or in Combination With Tranexamic Acid in the Treatment of Spontaneous Chronic Urticaria. Multicentric Controlled Randomized Study in Cross-over, Double-blind</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Grenoble</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Grenoble</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>
      Spontaneous chronic urticaria (UCS) is a disease that affects 1% of the general population&#xD;
      with a potentially severe impact on quality of life. Most patients respond favorably to&#xD;
      long-term antihistamine treatment, but sometimes it is necessary to give a high dose (4 times&#xD;
      the formal dose, Berlin consensus 2016). These high doses are often accompanied by side&#xD;
      effects requiring cessation of treatment. The therapeutic alternative is then omalizumab, an&#xD;
      expensive biotherapy. UCS is secondary to non-specific mast cell activation. It has been&#xD;
      shown to be associated with activation of fibrinolysis that correlates with the severity of&#xD;
      symptoms. Patients with UCS resistant to levocetirizine were shown to have higher D-dimer&#xD;
      levels than patients who responded to antihistamines. Tranexamic acid is a molecule with&#xD;
      antifibrinolytic propertiesSeveral cases of severe chronic urticaria responding favorably to&#xD;
      treatment with tranexamic acid have been reported. In our department, Investigators also&#xD;
      noticed the improvement of some of their patients on tranexamic acid. The combination of&#xD;
      these two treatments appears to be synergistic: action on histamine receptors and control of&#xD;
      fibrinolysis.&#xD;
&#xD;
      The investigators propose to evaluate the association of tranexamic acid and levocetirizine&#xD;
      for the treatment of chronic spontaneous urticaria.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Multicentric controlled randomized crossover study, double-blind To evaluate the efficacy and&#xD;
      safety of levocetirizine 10mg / day + tranexamic acid (AT) 2g / day versus levocetirizine&#xD;
      20mg / day alone in the chronic treatment of chronic urticaria evaluated at 4 weeks.&#xD;
&#xD;
      A hierarchical analysis will be implemented in the following order:&#xD;
&#xD;
        1. Non-inferiority of the combination levocetirizine 10 mg / day + tranexamic acid (TA) 2 g&#xD;
           / day versus levocetirizine alone 20 mg / day in terms of effectiveness&#xD;
&#xD;
        2. Superiority of the combination levocetirizine 10 mg / day + tranexamic acid (AT) 2 g /&#xD;
           day versus levocetirizine alone 20 mg / day in terms of tolerance&#xD;
&#xD;
        3. Superiority of levocetirizine 10mg / day + tranexamic acid (AT) 2g / day versus&#xD;
           levocetirizine alone 20mg / day in terms of effectiveness Each objective will be tested&#xD;
           sequentially if and only if the previous objective is validated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">December 10, 2019</start_date>
  <completion_date type="Anticipated">September 2022</completion_date>
  <primary_completion_date type="Anticipated">September 2022</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Multicentric controlled randomized crossover study, double-blind</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Double blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Evolution of the Urticaria Activity Score 7 (UAS7)</measure>
    <time_frame>28 days</time_frame>
    <description>Evolution of the UAS7 score between the beginning (J0) and the end (J28) of the treatment period. To calculate the score, the patient rates the number of papules and itching intensity from 0 to 3 daily for 7 days. 0 corresponds to no papules and no itching, 3 corresponds to more than 50 papules per 24h and intense itching that can cause daily life. This makes a score of 0 to 6 per day accumulated over 7 days, ranging from 0 to 42.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tolerance of the association tranexamic acid and levocetirizine</measure>
    <time_frame>28 days</time_frame>
    <description>Number of adverse events</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To demonstrate the non-inferiority of levocetirizine 10mg / day + tranexamic acid (AT) 2g / day versus levocetirizine alone 20mg / day in terms of efficacy on the Angioedema Activity Score (AAS)</measure>
    <time_frame>28 days</time_frame>
    <description>Evolution of the AAS score between the beginning (J0) and the end (J28) of the end of treatment. The AAS score is a The AAS consists of 5 questions as well as an opening question. A score between 0 and 3 is assigned to every answer field. The question scores are summed up to an AAS day sum score, 7 AAS day sum scores to an AAS week sum score (AAS7). Accordingly, the minimum and maximum possible AAS scores are 0-15 (AAS day sum score), 0-105 (AAS7).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical characteristics of responders</measure>
    <time_frame>28 days</time_frame>
    <description>Identify the clinical characteristics of responders to the combination rather than antihistamines alone.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Chronic Spontaneous Urticaria</condition>
  <arm_group>
    <arm_group_label>Association drugs</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>levocetirizine 10mg/day + tranexamic acid (AT) 2g/day for a month</description>
  </arm_group>
  <arm_group>
    <arm_group_label>one drug</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Levocetirizine 20 mg/day for a month</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>association of levocetirizine and tranexamic acid</intervention_name>
    <description>levocetirizine 10 mg/day + tranexamic acid 2 g/day</description>
    <arm_group_label>Association drugs</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Levocetirizine only</intervention_name>
    <description>levocetirizine 20 mg/day</description>
    <arm_group_label>one drug</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with spontaneous chronic urticaria, according to the criteria of the European&#xD;
             Academy of Allergology and Clinical Immunology (EAACI) in agreement with the European&#xD;
             Dermatology Forum (EDF), and the World Allergy Organization (WAO), corresponding to an&#xD;
             association of the following symptoms : urticarial eruptions and / or recurrent&#xD;
             angioedema for at least 6 weeks&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Urticaria associated with a specific systemic disease including cutaneous and systemic&#xD;
             mastocytosis, urticarial vasculitis, autoinflammatory diseases associated with&#xD;
             cryopyrin&#xD;
&#xD;
          -  Bradykinin angioedema and isolated angioedema whose origin is not clearly attributable&#xD;
             to spontaneous chronic urticaria.&#xD;
&#xD;
          -  Presence of a contraindication to tranexamic acid and to levocetirizine&#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>Laurence BOUILLET, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Internal Medicine - University Hospital Grenoble-Alpes</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Raouf ZOUGLECH, MDS</last_name>
    <phone>4 76 76 78 38</phone>
    <phone_ext>0033</phone_ext>
    <email>rzouglech@chu-grenoble.fr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Tiphaine Montagnon</last_name>
    <phone>4 76 76 68 14</phone>
    <phone_ext>0033</phone_ext>
    <email>tmontagnon@chu-grenoble.fr</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>CHU Grenoble-Alpes</name>
      <address>
        <city>Grenoble</city>
        <zip>38043</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mélanie Arnaud</last_name>
      <phone>4 76 76 78 38</phone>
      <phone_ext>0033</phone_ext>
    </contact>
    <investigator>
      <last_name>Laurence BOUILLET, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>October 17, 2018</study_first_submitted>
  <study_first_submitted_qc>December 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 28, 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>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Urticaria</mesh_term>
    <mesh_term>Chronic Urticaria</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cetirizine</mesh_term>
    <mesh_term>Tranexamic Acid</mesh_term>
    <mesh_term>Levocetirizine</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03789422
org study id: TACUS- 38RC18.103
nct id: NCT03789422
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Spontaneous chronic urticaria (UCS) is a disease that affects 1% of the general population
      with a potentially severe impact on quality of life. Most patients respond favorably to
      long-term antihistamine treatment, but sometimes it is necessary to give a high dose (4 times
      the formal dose, Berlin consensus 2016). These high doses are often accompanied by side
      effects requiring cessation of treatment. The therapeutic alternative is then omalizumab, an
      expensive biotherapy. UCS is secondary to non-specific mast cell activation. It has been
      shown to be associated with activation of fibrinolysis that correlates with the severity of
      symptoms. Patients with UCS resistant to levocetirizine were shown to have higher D-dimer
      levels than patients who responded to antihistamines. Tranexamic acid is a molecule with
      antifibrinolytic propertiesSeveral cases of severe chronic urticaria responding favorably to
      treatment with tranexamic acid have been reported. In our department, Investigators also
      noticed the improvement of some of their patients on tranexamic acid. The combination of
      these two treatments appears to be synergistic: action on histamine receptors and control of
      fibrinolysis.

      The investigators propose to evaluate the association of tranexamic acid and levocetirizine
      for the treatment of chronic spontaneous urticaria.
Multicentric controlled randomized crossover study, double-blind To evaluate the efficacy and
      safety of levocetirizine 10mg / day + tranexamic acid (AT) 2g / day versus levocetirizine
      20mg / day alone in the chronic treatment of chronic urticaria evaluated at 4 weeks.

      A hierarchical analysis will be implemented in the following order:

        1. Non-inferiority of the combination levocetirizine 10 mg / day + tranexamic acid (TA) 2 g
           / day versus levocetirizine alone 20 mg / day in terms of effectiveness

        2. Superiority of the combination levocetirizine 10 mg / day + tranexamic acid (AT) 2 g /
           day versus levocetirizine alone 20 mg / day in terms of tolerance

        3. Superiority of levocetirizine 10mg / day + tranexamic acid (AT) 2g / day versus
           levocetirizine alone 20mg / day in terms of effectiveness Each objective will be tested
           sequentially if and only if the previous objective is validated.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Multicentric controlled randomized crossover study, double-blind
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: Double blind
measure: Evolution of the Urticaria Activity Score 7 (UAS7)
time frame: 28 days
description: Evolution of the UAS7 score between the beginning (J0) and the end (J28) of the treatment period. To calculate the score, the patient rates the number of papules and itching intensity from 0 to 3 daily for 7 days. 0 corresponds to no papules and no itching, 3 corresponds to more than 50 papules per 24h and intense itching that can cause daily life. This makes a score of 0 to 6 per day accumulated over 7 days, ranging from 0 to 42.
measure: Tolerance of the association tranexamic acid and levocetirizine
time frame: 28 days
description: Number of adverse events
measure: To demonstrate the non-inferiority of levocetirizine 10mg / day + tranexamic acid (AT) 2g / day versus levocetirizine alone 20mg / day in terms of efficacy on the Angioedema Activity Score (AAS)
time frame: 28 days
description: Evolution of the AAS score between the beginning (J0) and the end (J28) of the end of treatment. The AAS score is a The AAS consists of 5 questions as well as an opening question. A score between 0 and 3 is assigned to every answer field. The question scores are summed up to an AAS day sum score, 7 AAS day sum scores to an AAS week sum score (AAS7). Accordingly, the minimum and maximum possible AAS scores are 0-15 (AAS day sum score), 0-105 (AAS7).
measure: Clinical characteristics of responders
time frame: 28 days
description: Identify the clinical characteristics of responders to the combination rather than antihistamines alone.
arm group label: Association drugs
arm group type: Active Comparator
description: levocetirizine 10mg/day + tranexamic acid (AT) 2g/day for a month
arm group label: one drug
arm group type: Active Comparator
description: Levocetirizine 20 mg/day for a month
intervention type: Drug
intervention name: association of levocetirizine and tranexamic acid
description: levocetirizine 10 mg/day + tranexamic acid 2 g/day
arm group label: Association drugs
intervention type: Drug
intervention name: Levocetirizine only
description: levocetirizine 20 mg/day
arm group label: one drug
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Laurence BOUILLET, PhD
role: Principal Investigator
affiliation: Internal Medicine - University Hospital Grenoble-Alpes
last name: Raouf ZOUGLECH, MDS
phone: 4 76 76 78 38
phone ext: 0033
email: rzouglech@chu-grenoble.fr
last name: Tiphaine Montagnon
phone: 4 76 76 68 14
phone ext: 0033
email: tmontagnon@chu-grenoble.fr
facility: 
status: Recruiting
contact: 
investigator: 
country: France
responsible party type: Sponsor
mesh term: Urticaria
mesh term: Chronic Urticaria
mesh term: Cetirizine
mesh term: Tranexamic Acid
mesh term: Levocetirizine