<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/NCT03825757</url>
  </required_header>
  <id_info>
    <org_study_id>TYH2018203</org_study_id>
    <secondary_id>2017-001570-42</secondary_id>
    <nct_id>NCT03825757</nct_id>
  </id_info>
  <brief_title>Aggravated Airway Inflammation: Research on Genomics and Optimal Medical Care (AirGOs-medical)</brief_title>
  <acronym>AirGOs-med</acronym>
  <official_title>Aggravated Airway Inflammation: Research on Genomics and Optimal Medical Care (AirGOs-medical)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sanna Salmi</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Helsinki</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Helsinki University Central 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>
      The study is performed as a randomized double-blinded prospective controlled trial. A total&#xD;
      of 72 adult Acetyl salicylic acid (ASA) -exacerbated respiratory disease (AERD) -patients&#xD;
      with uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) will be recruited. Those&#xD;
      negative to ASA-challenge test will not enter the Clinical Trial . All patients entering the&#xD;
      Clinical Trial, have undergone earlier ethmoidal surgery (partial/total) and have not gained&#xD;
      disease control. F-helicobacter antigen is tested and treatment is given if indicated. The&#xD;
      patients are recruited at the Helsinki University Hospital (HUH). The study will be monitored&#xD;
      by a professional monitor. Electronic CRF and paper/electronic patient questionnaires&#xD;
      provided by HUS will be used (eCRF and patient questionnairea, Granitics).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Randomization and the treatment arms I-II: The patients are randomized to two treatment arms&#xD;
      I) ASA- desensitization po tablet daily for 11 months (n=36) II) Placebo po tablet daily for&#xD;
      11 months (n=18).&#xD;
&#xD;
      ASA challenge and desensitization (Primaspan) /Placebo: is conducted according to modified&#xD;
      international protocol. FEV1 should be at least 1.5 L and &gt; 60% of predicted before challenge&#xD;
      or desensitization. On the first day every patient will receive 25 mg + 25 mg ASA at a&#xD;
      hospital setting. On the second day every patient will receive 50 mg + 25 mg ASA at a&#xD;
      hospital setting. On the third day every patient will receive 75 mg + 25 mg ASA at a hospital&#xD;
      setting. On the fourth day every patient will receive 100 mg + 25 mg ASA at a hospital&#xD;
      setting.&#xD;
&#xD;
      During the ASA challenge, patient who is ASA-challenge positive is then randomized and starts&#xD;
      the trial so that he/she uses blinded ½ tablet of 250 mg ASA or ½ tablet of placebo daily at&#xD;
      home for the next 1 month. After this period of 1 month, the dosing is increased at hospital&#xD;
      setting, so that the patient receives blindly 250 mg ASA 1/2 tablet + 1/2 tablet or placebo&#xD;
      1/2 tablet + 1/2 tablet. Thereafter he/she will continue using blindly 250 mg ASA 1 tablet or&#xD;
      placebo 1 tablet daily at home for the next 10 months. If the patient does not tolerate the&#xD;
      up-dosing of ASA/placebo, he/she will continue using blindly ½ tablet of 250 mg ASA/placebo&#xD;
      daily at home for the next 10 months. The total duration of the ASA/placebo treatment is 11&#xD;
      months. We additionally take nasal, blood and urine samples during the trial.&#xD;
&#xD;
      Follow-ups. The symptom questionnaire and interview of side-effects are performed during each&#xD;
      visit. Lung function (eNO, nNO, PEF, spirometry) is monitored and the patient will visit&#xD;
      doctor and/or nurse at 1, 5, 11, and 12 months post-starting with the treatment. Samples are&#xD;
      taken during recruitment visit, before and after ASA-challenge and at 5, 11 and 12 months&#xD;
      post-starting with the treatment. We also monitor side-effects, exacerbations, need of&#xD;
      medication (po. cortisocteroids; antibiotics) and satisfaction to treatment.&#xD;
&#xD;
      Primary end point is change in nasal endoscopic nasal polyp score at -4 days vs. +11 months&#xD;
      post-randomization. Secondary end point is change in Sinonasal Outcome Test -22 (SNOT-22)&#xD;
      score at -4 days vs. +11 months post-randomization, and change in relative Forced expiratory&#xD;
      volume in 1 second (FEV1 %) without bronchodilator at -1 month vs. +11 months&#xD;
      post-randomization.&#xD;
&#xD;
      Safety (complications, adverse effects), costs and loss of productivity between study arms&#xD;
      will be compared.&#xD;
&#xD;
      Trial medication will be discontinued, if surgery is needed before the end of follow-up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 31, 2019</start_date>
  <completion_date type="Anticipated">March 31, 2027</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2025</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Randomized double-blinded controlled trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Care Provider)</masking>
    <masking_description>The IMP producer (Galena Pharma Ltd., Kuopio, Finland) has packed the IMP according to study protocol and provides a code of each product. The IMP is used double-blinded in their numbered order. The key of the codes are stored in closed envelopes in Hospital´s locked closet. HYKS-institute performs regular study monitoring</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in endoscopic Nasal polyp score of both sides of the nasal cavity.</measure>
    <time_frame>at -4 days vs. at 11 months post-randomization</time_frame>
    <description>Change means differences between at time -4 days versus (vs.) at time +11 months post-randomization. Minimum value is 0. Maximum value is 8. A higher score means worse outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Sinonasal outcome test 22 (SNOT22). Validated nose-specific quality of life questionnaire, 0-110 points.</measure>
    <time_frame>at -4 days vs. at 11 months post-randomization</time_frame>
    <description>Change means differences between at time -4 days vs. +11 months post-randomization. A higher score means worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Relative forced expiratory volume in 1 second (FEV1%) without bronchodilator.</measure>
    <time_frame>at -1 month vs. at 11 months post-randomization</time_frame>
    <description>Change means differences between at time -1 month vs. +11 months post-randomization. A higher value means better outcome. FEV1% is measured by Spirometry.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Chronic Rhinosinusitis (Diagnosis)</condition>
  <arm_group>
    <arm_group_label>Primaspan tablet 250 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Primaspan tablet 250 mg (Acetyl salicylic acid): 1/2 tablet once daily during 1 month. 1 tablet once daily during 10 months. If not tolerated the dose 1 tablet x1/day, the patient is allowed to continue with the dose of 1/2 tablet x1/day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo tablet</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo Oral Tablet: 1/2 tablet once daily during 1 month. 1 tablet once daily during 10 months. If not tolerated the dose 1 tablet x1/day, the patient is allowed to continue with the dose of 1/2 tablet x1/day.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>Placebo Oral Tablet</description>
    <arm_group_label>Placebo tablet</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acetyl Salicylic Acid</intervention_name>
    <description>Primaspan 250 mg tablet Acetyl Salicylic Acid</description>
    <arm_group_label>Primaspan tablet 250 mg</arm_group_label>
    <other_name>Primaspan 250 mg tablet</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria: ALL these need to be positive:&#xD;
&#xD;
          -  Endoscopic nasal polyp score ≥4&#xD;
&#xD;
          -  SNOT-22 ≥30&#xD;
&#xD;
          -  Sinus Computed tomography Lund-Mackay score ≥14. The new sinus CT scans are needed if&#xD;
             the previous sinus CT scans have been performed over 36 months before recruitment&#xD;
             visit or if there is a suspicion of complication of CRS (f.ex. mucocele, invasive&#xD;
             fungal rhinosinusitis)&#xD;
&#xD;
          -  ≥1 previous partial/total ethmoidectomy surgery.&#xD;
&#xD;
        In addition, patient should have a history of at least one of the following:&#xD;
&#xD;
        &gt;1 oral corticosteroids during the past two years &gt;3 antibiotic courses during the past two&#xD;
        years. In patients with contraindication/adverse effects in using oral steroids additional&#xD;
        criteria are not required.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  complication of CRS (f.e. mucocele, invasive fungal rhinosinusitis)&#xD;
&#xD;
          -  bleeding diathesis&#xD;
&#xD;
          -  pregnancy/ breastfeeding&#xD;
&#xD;
          -  cystic fibrosis&#xD;
&#xD;
          -  primary ciliary dyskinesia (PCD)&#xD;
&#xD;
          -  sarcoidosis&#xD;
&#xD;
          -  granulomatosis with polyangitis (GPA)&#xD;
&#xD;
          -  eosinophilic granulomatosis with polyangitis (EGPA)&#xD;
&#xD;
          -  immunosuppression (diagnosed Spesific antibody deficiency (SAD), CVI, HIV&#xD;
&#xD;
          -  use of biologicals/immunosuppressive medication&#xD;
&#xD;
          -  immunotherapy&#xD;
&#xD;
          -  Daily use of systemic corticosteroids (Prednisolon 10mg or equivalent) -communication&#xD;
             problems (f.e. neurological/psychiatric disease, language skills) -unlikely to comply&#xD;
&#xD;
          -  other severe disease&#xD;
&#xD;
          -  uncontrolled asthma&#xD;
&#xD;
          -  ASA-challenge negative&#xD;
&#xD;
          -  gastric ulcer&#xD;
&#xD;
          -  anticoagulant treatment&#xD;
&#xD;
          -  SSRI-depression medication&#xD;
&#xD;
          -  beta-blocker&#xD;
&#xD;
          -  severe chronic urticaria&#xD;
&#xD;
          -  ASA anaphylaxis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sanna Toppila-Salmi, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Helsinki University Central Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sanna Toppila-Salmi, MD PhD</last_name>
    <phone>+358505431421</phone>
    <email>sanna.salmi@helsinki.fi</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Annina Lyly, MD PhD</last_name>
    <phone>+358505455051</phone>
    <email>annina.lyly@hus.fi</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Helsinki University Hospital</name>
      <address>
        <city>Helsinki</city>
        <zip>00029</zip>
        <country>Finland</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sanna K Toppila-Salmi, MD PhD</last_name>
      <phone>+358505431421</phone>
      <email>sanna.salmi@helsinki.fi</email>
    </contact>
    <contact_backup>
      <last_name>Annina Lyly, MD PHD</last_name>
      <phone>+358505455051</phone>
      <email>annina.lyly@hus.fi</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Finland</country>
  </location_countries>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/30216468</url>
    <description>Diagnosis and management of NSAID-Exacerbated Respiratory Disease (N-ERD)-a EAACI position paper.</description>
  </link>
  <link>
    <url>https://www.ncbi.nlm.nih.gov/pubmed/30575459</url>
    <description>Aspirin-Exacerbated Respiratory Disease. Publication.</description>
  </link>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>January 26, 2019</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 31, 2019</study_first_posted>
  <last_update_submitted>August 5, 2022</last_update_submitted>
  <last_update_submitted_qc>August 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Helsinki University Central Hospital</investigator_affiliation>
    <investigator_full_name>Sanna Salmi</investigator_full_name>
    <investigator_title>Senior Consultant Otorhinolaryngologist, PI</investigator_title>
  </responsible_party>
  <keyword>chronic rhinosinusitis with nasal polyps</keyword>
  <keyword>Acetyl salicylic acid exacerbated respiratory disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aspirin</mesh_term>
    <mesh_term>Salicylic Acid</mesh_term>
    <mesh_term>Salicylates</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>The data is owned by Helsinki University Hospital and University of Helsinki.</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/NCT03825757
org study id: TYH2018203
secondary id: 2017-001570-42
nct id: NCT03825757
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The study is performed as a randomized double-blinded prospective controlled trial. A total
      of 72 adult Acetyl salicylic acid (ASA) -exacerbated respiratory disease (AERD) -patients
      with uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) will be recruited. Those
      negative to ASA-challenge test will not enter the Clinical Trial . All patients entering the
      Clinical Trial, have undergone earlier ethmoidal surgery (partial/total) and have not gained
      disease control. F-helicobacter antigen is tested and treatment is given if indicated. The
      patients are recruited at the Helsinki University Hospital (HUH). The study will be monitored
      by a professional monitor. Electronic CRF and paper/electronic patient questionnaires
      provided by HUS will be used (eCRF and patient questionnairea, Granitics).
Randomization and the treatment arms I-II: The patients are randomized to two treatment arms
      I) ASA- desensitization po tablet daily for 11 months (n=36) II) Placebo po tablet daily for
      11 months (n=18).

      ASA challenge and desensitization (Primaspan) /Placebo: is conducted according to modified
      international protocol. FEV1 should be at least 1.5 L and > 60% of predicted before challenge
      or desensitization. On the first day every patient will receive 25 mg + 25 mg ASA at a
      hospital setting. On the second day every patient will receive 50 mg + 25 mg ASA at a
      hospital setting. On the third day every patient will receive 75 mg + 25 mg ASA at a hospital
      setting. On the fourth day every patient will receive 100 mg + 25 mg ASA at a hospital
      setting.

      During the ASA challenge, patient who is ASA-challenge positive is then randomized and starts
      the trial so that he/she uses blinded ½ tablet of 250 mg ASA or ½ tablet of placebo daily at
      home for the next 1 month. After this period of 1 month, the dosing is increased at hospital
      setting, so that the patient receives blindly 250 mg ASA 1/2 tablet + 1/2 tablet or placebo
      1/2 tablet + 1/2 tablet. Thereafter he/she will continue using blindly 250 mg ASA 1 tablet or
      placebo 1 tablet daily at home for the next 10 months. If the patient does not tolerate the
      up-dosing of ASA/placebo, he/she will continue using blindly ½ tablet of 250 mg ASA/placebo
      daily at home for the next 10 months. The total duration of the ASA/placebo treatment is 11
      months. We additionally take nasal, blood and urine samples during the trial.

      Follow-ups. The symptom questionnaire and interview of side-effects are performed during each
      visit. Lung function (eNO, nNO, PEF, spirometry) is monitored and the patient will visit
      doctor and/or nurse at 1, 5, 11, and 12 months post-starting with the treatment. Samples are
      taken during recruitment visit, before and after ASA-challenge and at 5, 11 and 12 months
      post-starting with the treatment. We also monitor side-effects, exacerbations, need of
      medication (po. cortisocteroids; antibiotics) and satisfaction to treatment.

      Primary end point is change in nasal endoscopic nasal polyp score at -4 days vs. +11 months
      post-randomization. Secondary end point is change in Sinonasal Outcome Test -22 (SNOT-22)
      score at -4 days vs. +11 months post-randomization, and change in relative Forced expiratory
      volume in 1 second (FEV1 %) without bronchodilator at -1 month vs. +11 months
      post-randomization.

      Safety (complications, adverse effects), costs and loss of productivity between study arms
      will be compared.

      Trial medication will be discontinued, if surgery is needed before the end of follow-up.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized double-blinded controlled trial
primary purpose: Treatment
masking: Single (Care Provider)
masking description: The IMP producer (Galena Pharma Ltd., Kuopio, Finland) has packed the IMP according to study protocol and provides a code of each product. The IMP is used double-blinded in their numbered order. The key of the codes are stored in closed envelopes in Hospital´s locked closet. HYKS-institute performs regular study monitoring
measure: Change in endoscopic Nasal polyp score of both sides of the nasal cavity.
time frame: at -4 days vs. at 11 months post-randomization
description: Change means differences between at time -4 days versus (vs.) at time +11 months post-randomization. Minimum value is 0. Maximum value is 8. A higher score means worse outcome.
measure: Change in Sinonasal outcome test 22 (SNOT22). Validated nose-specific quality of life questionnaire, 0-110 points.
time frame: at -4 days vs. at 11 months post-randomization
description: Change means differences between at time -4 days vs. +11 months post-randomization. A higher score means worse outcome.
measure: Change in the Relative forced expiratory volume in 1 second (FEV1%) without bronchodilator.
time frame: at -1 month vs. at 11 months post-randomization
description: Change means differences between at time -1 month vs. +11 months post-randomization. A higher value means better outcome. FEV1% is measured by Spirometry.
arm group label: Primaspan tablet 250 mg
arm group type: Experimental
description: Primaspan tablet 250 mg (Acetyl salicylic acid): 1/2 tablet once daily during 1 month. 1 tablet once daily during 10 months. If not tolerated the dose 1 tablet x1/day, the patient is allowed to continue with the dose of 1/2 tablet x1/day.
arm group label: Placebo tablet
arm group type: Placebo Comparator
description: Placebo Oral Tablet: 1/2 tablet once daily during 1 month. 1 tablet once daily during 10 months. If not tolerated the dose 1 tablet x1/day, the patient is allowed to continue with the dose of 1/2 tablet x1/day.
intervention type: Drug
intervention name: Placebo Oral Tablet
description: Placebo Oral Tablet
arm group label: Placebo tablet
other name: Placebo
intervention type: Drug
intervention name: Acetyl Salicylic Acid
description: Primaspan 250 mg tablet Acetyl Salicylic Acid
arm group label: Primaspan tablet 250 mg
other name: Primaspan 250 mg tablet
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Sanna Toppila-Salmi, MD PhD
role: Principal Investigator
affiliation: Helsinki University Central Hospital
last name: Sanna Toppila-Salmi, MD PhD
phone: +358505431421
email: sanna.salmi@helsinki.fi
last name: Annina Lyly, MD PhD
phone: +358505455051
email: annina.lyly@hus.fi
facility: 
status: Recruiting
contact: 
contact backup: 
country: Finland
url: https://www.ncbi.nlm.nih.gov/pubmed/30216468
description: Diagnosis and management of NSAID-Exacerbated Respiratory Disease (N-ERD)-a EAACI position paper.
url: https://www.ncbi.nlm.nih.gov/pubmed/30575459
description: Aspirin-Exacerbated Respiratory Disease. Publication.
responsible party type: Sponsor-Investigator
investigator affiliation: Helsinki University Central Hospital
investigator full name: Sanna Salmi
investigator title: Senior Consultant Otorhinolaryngologist, PI
mesh term: Inflammation
mesh term: Aspirin
mesh term: Salicylic Acid
mesh term: Salicylates
sharing ipd: No
ipd description: The data is owned by Helsinki University Hospital and University of Helsinki.