<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/NCT04476628</url>
  </required_header>
  <id_info>
    <org_study_id>H20-00842</org_study_id>
    <nct_id>NCT04476628</nct_id>
  </id_info>
  <brief_title>Efficacy of Budesonide Via Delayed Release vs Immediate Release</brief_title>
  <official_title>Prospective Double-Cohort Study: Comparing Efficacy of Budesonide Via Delayed Release vs Immediate Release After Administration in the Lying Head Back Position</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Paul's Hospital, Canada</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>St. Paul's Hospital, Canada</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to compare the efficacy of intranasal budesonide administration with&#xD;
      lying head back position and a 5 mins time to release of medication (5MR) compared to 1 min&#xD;
      time to release (1MR) in chronic rhinosinusitis patients (CRS). Participants will be&#xD;
      instructed to administer via mucosal automatization device (MAD) with either of the two&#xD;
      treatment approaches daily for 5 to 7 days per week and 8 weeks total. This is a crossover&#xD;
      study design so each participants will be placed in the other treatment approach for an&#xD;
      additional 8 weeks of treatment. Moreover, there will be a &quot;washout&quot; of 2 weeks after&#xD;
      baseline assessment and before the first treatment, as well as a second &quot;washout&quot; of 2 weeks&#xD;
      between the two treatment approaches. The participants will also complete study related&#xD;
      procedures such as endoscopic evaluation, cultures, and two questionnaires throughout the&#xD;
      study period. The investigators hypothesize that Budesonide delivered to the sinuses with a 5&#xD;
      minute time to release of medication will be more effective at decreasing inflammation when&#xD;
      compared to a 1 minute time to release of medication after administration.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective&#xD;
&#xD;
      To compare the efficacy of 1 minute versus 5 minutes time to release of budesonide with lying&#xD;
      head back position following administration via mucosal atomization device (MAD).&#xD;
&#xD;
      Hypothesis&#xD;
&#xD;
      Budesonide delivered to the sinuses with lying head back position and a 5 minute time to&#xD;
      release (5MR) of medication will be more effective at decreasing inflammation both&#xD;
      objectively and subjectively when compared to 1 minute time to release (1MR) of medication&#xD;
      after administration.&#xD;
&#xD;
      Baseline and Follow-up Visits Evaluation:&#xD;
&#xD;
      The following information will be obtained from each participant&#xD;
&#xD;
      Baseline Demographic Data: Age, sex, smoking status, CRS subtype, pre-existing comorbidities,&#xD;
      history of asthma, history of previous surgery, history of previous medications including&#xD;
      oral and inhaled corticosteroids.&#xD;
&#xD;
      Clinical Data: Modified Lund-Kennedy (MLK) scores, sinonasal cultures, Sino-nasal Outcome&#xD;
      Test-22 (SNOT-22), EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) scores, and culture.&#xD;
&#xD;
      Conduct of Study:&#xD;
&#xD;
      The proposed study is a single blind randomized, controlled crossover study at of 20 weeks in&#xD;
      duration. Participants who have CRS and who meet the inclusion and exclusion criteria, will&#xD;
      be invited to participate in this study.&#xD;
&#xD;
      Participants will undergo a 2 week &quot;washout&quot; period before starting their respective&#xD;
      administration method. The first administration methods will be once daily for 8 weeks in&#xD;
      duration. This is then followed by an additional &quot;washout&quot; period of 2 weeks. Finally,&#xD;
      participants will switch to the other administration method for an additional treatment&#xD;
      duration of daily application for 8 weeks. The goal is to assess which administration method&#xD;
      is more effective. Participants will be asked to administer budesonide daily with a minimum&#xD;
      requirement of at least five days a week to ensure changes seen are related to the&#xD;
      appropriate treatment arm. The &quot;washout&quot; period will involve standard of care daily&#xD;
      non-medicated intranasal saline irrigation. Data will be collected at baseline, 2 weeks, 10&#xD;
      weeks, 12 weeks, and lastly 20 weeks follow-up visit. SNOT-22 questionnaires, EQ-5D-5L&#xD;
      questionnaires, endoscopic evaluation, and Modified Lund Kennedy Scores will each be&#xD;
      completed at baseline and then again at 2 weeks, 10 weeks, 12 weeks, and 20 weeks.&#xD;
&#xD;
      Upon enrolment in the study, participants will be randomly divided to either start with 5MR&#xD;
      or 1MR administration methods through 1:1 block randomization. In addition, demographic data&#xD;
      and clinical data will be obtained by the investigators.&#xD;
&#xD;
      Management of Patient Care:&#xD;
&#xD;
      The clinical care remains the same for participants participating in this study; however,&#xD;
      there is a possibility that some participants will experience an increased frequency of&#xD;
      visits to the clinic with some being spaced 2 weeks apart. The increased appointments are&#xD;
      required to effectively transition each participants into the different treatment types and&#xD;
      also to acquire additional outcome measures. This will be clearly explained to each&#xD;
      participant to ensure that they are aware of the additional appointments compared to standard&#xD;
      of care. Otherwise, there are no additional risks imposed on the study participants.&#xD;
      Participants have the right to withdraw from the study at any time. Participants who meet any&#xD;
      of the exclusion criteria that were not noted at the beginning of the study will be removed&#xD;
      from this study and the physician will discuss the future management options with the&#xD;
      participant.&#xD;
&#xD;
      Sample Size:&#xD;
&#xD;
      A recruitment goal of 60 participants (30 participants per study arm) is expected to&#xD;
      demonstrate an effect for the study. To account for a drop-out rate of 25% the investigators&#xD;
      plan to recruit 40 participants in each arm.&#xD;
&#xD;
      The washout periods included in the crossover study design will allow for more control in&#xD;
      regards to reducing confounding variables. In particular, this allows participants to start&#xD;
      at a similar baseline by using the same standard of treatment with Budesonide for the 2 weeks&#xD;
      of washout before going into the 5MR or 1MR treatments.&#xD;
&#xD;
      Analysis:&#xD;
&#xD;
      Descriptive statistics will be used to analyze the baseline characteristic data and the data&#xD;
      from the administered surveys and objective findings of cultures and MLK scores. In addition,&#xD;
      rigorous statistical analysis will be conducted on the Likert scale-based SNOT-22 and&#xD;
      EQ-5D-5L surveys. These analyses will include paired t tests with repeated measured ANOVA for&#xD;
      validation and confidence intervals.&#xD;
&#xD;
      Safety Monitoring:&#xD;
&#xD;
      Participants who experience signs and symptoms of budesonide reaction will be noted and the&#xD;
      code will be broken so that a discussion can occur between the research supervisor and the&#xD;
      participants regarding the use.&#xD;
&#xD;
      All expected and unexpected adverse events will be recorded and graded by the research&#xD;
      supervisor. Stable chronic conditions, which are present prior to the clinical trial entry&#xD;
      and do not worsen, are not considered adverse events and will be accounted for in the&#xD;
      participant's medical history.&#xD;
&#xD;
      During each participant visit, the research supervisor will ask appropriate questions and&#xD;
      perform a physical exam to elicit any adverse events. The research supervisor will also&#xD;
      review any relevant clinical data and laboratory investigations with the partcicpant. All&#xD;
      reportable adverse events will be recorded on appropriate case report form. The research&#xD;
      supervisor will also write the stop date, the severity of the AE and his judgment of the AE's&#xD;
      relationship to the study.&#xD;
&#xD;
      A Serious Adverse Event (SAE) is defined as an AE meeting one of the following:&#xD;
&#xD;
      Death occurring between Day 0 and 182 days (6 months) of the study. Life Threatening Event&#xD;
      (defined as a participant at immediate risk of death at the time of the event) In-participant&#xD;
      hospitalization or prolongation of existing hospitalization between Day 0 and 42 of the&#xD;
      study.&#xD;
&#xD;
      Results in a persistent or significant disability/incapacity In the event of SAE, the&#xD;
      research supervisor will discuss with the partcipant (or next of kin) whether there is a&#xD;
      relationship between the study and the SAE. If there is a relationship, the PI will be&#xD;
      responsible for coordinating care for the participant until the SAE has been addressed.&#xD;
&#xD;
      Pregnancy During the Trial Participants will be responsible for determining if they are&#xD;
      pregnant or become pregnant during the study. If participants notify the PI they are&#xD;
      pregnant, they will be removed from the study and the medical management options will be&#xD;
      discussed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Due to COVID-19, we didn't start this study&#xD;
  </why_stopped>
  <start_date type="Anticipated">February 1, 2021</start_date>
  <completion_date type="Anticipated">February 28, 2022</completion_date>
  <primary_completion_date type="Anticipated">January 31, 2022</primary_completion_date>
  <phase>Early Phase 1</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>Patients will be randomly divided to either start with 5MR or 1MR administration methods. They will undergo a 2 week &quot;washout&quot; period before starting their respective administration method. The first administration methods will be once daily for 8 weeks in duration. This is then followed by an additional &quot;washout&quot; period of 2 weeks. Finally, patients will switch to the other administration method for an additional treatment duration of daily application for 8 weeks. We will assess which administration method is more effective. Patients will be asked to administer budesonide daily with a minimum requirement of at least five days a week to ensure changes seen are related to the appropriate treatment arm. The &quot;washout&quot; period will involve standard of care daily non-medicated intranasal saline irrigation. Data will be collected at baseline, 2 weeks, 10 weeks, 12 weeks, and lastly 20 weeks follow-up visit.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Modified Lund Kennedy Score</measure>
    <time_frame>baseline and 20 weeks</time_frame>
    <description>This score is based on the endoscopic assessment of polyps, edema, and discharge and are each given score 0-2. It is out of a total score of 12 with higher scores indicating a worse outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Sinonasal-Outcomes Test-22 (SNOT-22) Score</measure>
    <time_frame>baseline and 20 weeks</time_frame>
    <description>This is a standard of care baseline Sinonasal Outcome Test form that includes 22 questions about symptoms and social/emotional consequences of your nasal disorder. You will be asked to rate your problems as they have been over the past two weeks. An example of the questions is:&#xD;
Need to blow nose&#xD;
Sneezing It is out of a total of 110 and higher scores mean a worse outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Score</measure>
    <time_frame>baseline and 20 weeks</time_frame>
    <description>This is a questionnaire that asks six multiple-choice questions about your mobility, self-care, usual activities, pain/discomfort, anxiety/depression, and overall health. It is out of a total score of 100 and higher scores mean a worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in sinus culture results</measure>
    <time_frame>baseline and 20 weeks</time_frame>
    <description>A swab will be taken from your nose to see if there are any bacteria or fungi present.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Chronic Rhinosinusitis (Diagnosis)</condition>
  <arm_group>
    <arm_group_label>Budesonide 5MR then 1MR</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All participants will administer budesonide daily via Mucosal Atomization Device (MAD) with a minimum requirement of at least five days a week for the duration of the study in this arm.&#xD;
st time period: Patients will undergo a 2 week &quot;washout&quot; period. The &quot;washout&quot; period will involve standard of care daily non-medicated intranasal saline irrigation.&#xD;
nd time period: 5MR administration method once daily for 8 weeks in duration.&#xD;
rd time period: Patients will undergo a 2 week &quot;washout&quot; period of daily. The &quot;washout&quot; period will involve standard of care daily non-medicated intranasal saline irrigation.&#xD;
th time period: 1MR administration method once daily for 8 weeks in duration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Budesonide 1MR then 5MR</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All participants will administer budesonide daily via Mucosal Atomization Device (MAD) with a minimum requirement of at least five days a week for the duration of the study in this arm.&#xD;
st time period: Patients will undergo a 2 week &quot;washout&quot; period. The &quot;washout&quot; period will involve standard of care daily non-medicated intranasal saline irrigation.&#xD;
nd time period: 1MR administration method once daily for 8 weeks in duration.&#xD;
rd time period: Patients will undergo a 2 week &quot;washout&quot; period of daily. The &quot;washout&quot; period will involve standard of care daily non-medicated intranasal saline irrigation.&#xD;
th time period: 5MR administration method once daily for 8 weeks in duration.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Budesonide</intervention_name>
    <description>Budesonide is a corticosteroid that is commonly used intranasally to treat CRS.</description>
    <arm_group_label>Budesonide 1MR then 5MR</arm_group_label>
    <arm_group_label>Budesonide 5MR then 1MR</arm_group_label>
    <other_name>Pulmicort</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Mucosal Atomization Device</intervention_name>
    <description>MAD is a device used as an addition to a syringe to atomize medication to increase area of distribution. It is used to administer budesonide within the nasal passages and sinuses to administer medication for CRS.</description>
    <arm_group_label>Budesonide 1MR then 5MR</arm_group_label>
    <arm_group_label>Budesonide 5MR then 1MR</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>NeilMed squeeze bottle for Impregnated Nasal Saline Irrigation</intervention_name>
    <description>INSI is delivered using a NeilMed squeeze bottle. It is used to administer budesonide within the nasal passages and sinuses to administer medication for CRS.</description>
    <arm_group_label>Budesonide 1MR then 5MR</arm_group_label>
    <arm_group_label>Budesonide 5MR then 1MR</arm_group_label>
    <other_name>INSI</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients aged between 19 years and above&#xD;
&#xD;
          2. Patients with chronic or recurrent sinusitis (as defined by the American Academy of&#xD;
             Otolaryngology) with or without nasal polyposis or allergic fungal rhinosinusitis.&#xD;
&#xD;
          3. Patients currently on budesonide or being prescribed budesonide for the first time&#xD;
&#xD;
          4. Minimum Modified Lund Kennedy score of 2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Individuals unable to understand the purpose, methods and conduct of this study&#xD;
&#xD;
          2. Patients unwilling to provide informed consent&#xD;
&#xD;
          3. Are immuno-compromised, and have impairment in mucociliary function (e.g., cystic&#xD;
             fibrosis, Kartagener syndrome)&#xD;
&#xD;
          4. Have autoimmune diseases affecting the upper airway (eg Systemic lupus erythematosus,&#xD;
             Sjögren's syndrome, systemic sclerosis etc)&#xD;
&#xD;
          5. Have sinonasal tumors&#xD;
&#xD;
          6. Patients with a history of pituitary disease&#xD;
&#xD;
          7. Patients with a known hypersensitivity to cortisol, corticotropin, or cosyntropin&#xD;
&#xD;
          8. Recent use of systemic corticosteroids such as prednisone (within last 3 months)&#xD;
&#xD;
          9. Patients who are pregnant or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Amin JAver, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of British Columbia and St. Paul's Sinus Centre</affiliation>
  </overall_official>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>July 7, 2022</last_update_submitted>
  <last_update_submitted_qc>July 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>St. Paul's Hospital, Canada</investigator_affiliation>
    <investigator_full_name>Amin Javer</investigator_full_name>
    <investigator_title>Assistant Clinical Professor</investigator_title>
  </responsible_party>
  <keyword>Budesonide</keyword>
  <keyword>MAD</keyword>
  <keyword>CRS</keyword>
  <keyword>Head Position</keyword>
  <keyword>Timing of Release</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sinusitis</mesh_term>
    <mesh_term>Chronic Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Budesonide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>We will publish final outcomes as scientific paper.</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/NCT04476628
org study id: H20-00842
nct id: NCT04476628
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
The aim of this study is to compare the efficacy of intranasal budesonide administration with
      lying head back position and a 5 mins time to release of medication (5MR) compared to 1 min
      time to release (1MR) in chronic rhinosinusitis patients (CRS). Participants will be
      instructed to administer via mucosal automatization device (MAD) with either of the two
      treatment approaches daily for 5 to 7 days per week and 8 weeks total. This is a crossover
      study design so each participants will be placed in the other treatment approach for an
      additional 8 weeks of treatment. Moreover, there will be a "washout" of 2 weeks after
      baseline assessment and before the first treatment, as well as a second "washout" of 2 weeks
      between the two treatment approaches. The participants will also complete study related
      procedures such as endoscopic evaluation, cultures, and two questionnaires throughout the
      study period. The investigators hypothesize that Budesonide delivered to the sinuses with a 5
      minute time to release of medication will be more effective at decreasing inflammation when
      compared to a 1 minute time to release of medication after administration.
Objective

      To compare the efficacy of 1 minute versus 5 minutes time to release of budesonide with lying
      head back position following administration via mucosal atomization device (MAD).

      Hypothesis

      Budesonide delivered to the sinuses with lying head back position and a 5 minute time to
      release (5MR) of medication will be more effective at decreasing inflammation both
      objectively and subjectively when compared to 1 minute time to release (1MR) of medication
      after administration.

      Baseline and Follow-up Visits Evaluation:

      The following information will be obtained from each participant

      Baseline Demographic Data: Age, sex, smoking status, CRS subtype, pre-existing comorbidities,
      history of asthma, history of previous surgery, history of previous medications including
      oral and inhaled corticosteroids.

      Clinical Data: Modified Lund-Kennedy (MLK) scores, sinonasal cultures, Sino-nasal Outcome
      Test-22 (SNOT-22), EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) scores, and culture.

      Conduct of Study:

      The proposed study is a single blind randomized, controlled crossover study at of 20 weeks in
      duration. Participants who have CRS and who meet the inclusion and exclusion criteria, will
      be invited to participate in this study.

      Participants will undergo a 2 week "washout" period before starting their respective
      administration method. The first administration methods will be once daily for 8 weeks in
      duration. This is then followed by an additional "washout" period of 2 weeks. Finally,
      participants will switch to the other administration method for an additional treatment
      duration of daily application for 8 weeks. The goal is to assess which administration method
      is more effective. Participants will be asked to administer budesonide daily with a minimum
      requirement of at least five days a week to ensure changes seen are related to the
      appropriate treatment arm. The "washout" period will involve standard of care daily
      non-medicated intranasal saline irrigation. Data will be collected at baseline, 2 weeks, 10
      weeks, 12 weeks, and lastly 20 weeks follow-up visit. SNOT-22 questionnaires, EQ-5D-5L
      questionnaires, endoscopic evaluation, and Modified Lund Kennedy Scores will each be
      completed at baseline and then again at 2 weeks, 10 weeks, 12 weeks, and 20 weeks.

      Upon enrolment in the study, participants will be randomly divided to either start with 5MR
      or 1MR administration methods through 1:1 block randomization. In addition, demographic data
      and clinical data will be obtained by the investigators.

      Management of Patient Care:

      The clinical care remains the same for participants participating in this study; however,
      there is a possibility that some participants will experience an increased frequency of
      visits to the clinic with some being spaced 2 weeks apart. The increased appointments are
      required to effectively transition each participants into the different treatment types and
      also to acquire additional outcome measures. This will be clearly explained to each
      participant to ensure that they are aware of the additional appointments compared to standard
      of care. Otherwise, there are no additional risks imposed on the study participants.
      Participants have the right to withdraw from the study at any time. Participants who meet any
      of the exclusion criteria that were not noted at the beginning of the study will be removed
      from this study and the physician will discuss the future management options with the
      participant.

      Sample Size:

      A recruitment goal of 60 participants (30 participants per study arm) is expected to
      demonstrate an effect for the study. To account for a drop-out rate of 25% the investigators
      plan to recruit 40 participants in each arm.

      The washout periods included in the crossover study design will allow for more control in
      regards to reducing confounding variables. In particular, this allows participants to start
      at a similar baseline by using the same standard of treatment with Budesonide for the 2 weeks
      of washout before going into the 5MR or 1MR treatments.

      Analysis:

      Descriptive statistics will be used to analyze the baseline characteristic data and the data
      from the administered surveys and objective findings of cultures and MLK scores. In addition,
      rigorous statistical analysis will be conducted on the Likert scale-based SNOT-22 and
      EQ-5D-5L surveys. These analyses will include paired t tests with repeated measured ANOVA for
      validation and confidence intervals.

      Safety Monitoring:

      Participants who experience signs and symptoms of budesonide reaction will be noted and the
      code will be broken so that a discussion can occur between the research supervisor and the
      participants regarding the use.

      All expected and unexpected adverse events will be recorded and graded by the research
      supervisor. Stable chronic conditions, which are present prior to the clinical trial entry
      and do not worsen, are not considered adverse events and will be accounted for in the
      participant's medical history.

      During each participant visit, the research supervisor will ask appropriate questions and
      perform a physical exam to elicit any adverse events. The research supervisor will also
      review any relevant clinical data and laboratory investigations with the partcicpant. All
      reportable adverse events will be recorded on appropriate case report form. The research
      supervisor will also write the stop date, the severity of the AE and his judgment of the AE's
      relationship to the study.

      A Serious Adverse Event (SAE) is defined as an AE meeting one of the following:

      Death occurring between Day 0 and 182 days (6 months) of the study. Life Threatening Event
      (defined as a participant at immediate risk of death at the time of the event) In-participant
      hospitalization or prolongation of existing hospitalization between Day 0 and 42 of the
      study.

      Results in a persistent or significant disability/incapacity In the event of SAE, the
      research supervisor will discuss with the partcipant (or next of kin) whether there is a
      relationship between the study and the SAE. If there is a relationship, the PI will be
      responsible for coordinating care for the participant until the SAE has been addressed.

      Pregnancy During the Trial Participants will be responsible for determining if they are
      pregnant or become pregnant during the study. If participants notify the PI they are
      pregnant, they will be removed from the study and the medical management options will be
      discussed.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Patients will be randomly divided to either start with 5MR or 1MR administration methods. They will undergo a 2 week "washout" period before starting their respective administration method. The first administration methods will be once daily for 8 weeks in duration. This is then followed by an additional "washout" period of 2 weeks. Finally, patients will switch to the other administration method for an additional treatment duration of daily application for 8 weeks. We will assess which administration method is more effective. Patients will be asked to administer budesonide daily with a minimum requirement of at least five days a week to ensure changes seen are related to the appropriate treatment arm. The "washout" period will involve standard of care daily non-medicated intranasal saline irrigation. Data will be collected at baseline, 2 weeks, 10 weeks, 12 weeks, and lastly 20 weeks follow-up visit.
primary purpose: Treatment
masking: Single (Investigator)
measure: Change in Modified Lund Kennedy Score
time frame: baseline and 20 weeks
description: This score is based on the endoscopic assessment of polyps, edema, and discharge and are each given score 0-2. It is out of a total score of 12 with higher scores indicating a worse outcome.
measure: Change in Sinonasal-Outcomes Test-22 (SNOT-22) Score
time frame: baseline and 20 weeks
description: This is a standard of care baseline Sinonasal Outcome Test form that includes 22 questions about symptoms and social/emotional consequences of your nasal disorder. You will be asked to rate your problems as they have been over the past two weeks. An example of the questions is:
Need to blow nose
Sneezing It is out of a total of 110 and higher scores mean a worse outcome.
measure: Change EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Score
time frame: baseline and 20 weeks
description: This is a questionnaire that asks six multiple-choice questions about your mobility, self-care, usual activities, pain/discomfort, anxiety/depression, and overall health. It is out of a total score of 100 and higher scores mean a worse outcome.
measure: Change in sinus culture results
time frame: baseline and 20 weeks
description: A swab will be taken from your nose to see if there are any bacteria or fungi present.
arm group label: Budesonide 5MR then 1MR
arm group type: Other
description: All participants will administer budesonide daily via Mucosal Atomization Device (MAD) with a minimum requirement of at least five days a week for the duration of the study in this arm.
st time period: Patients will undergo a 2 week "washout" period. The "washout" period will involve standard of care daily non-medicated intranasal saline irrigation.
nd time period: 5MR administration method once daily for 8 weeks in duration.
rd time period: Patients will undergo a 2 week "washout" period of daily. The "washout" period will involve standard of care daily non-medicated intranasal saline irrigation.
th time period: 1MR administration method once daily for 8 weeks in duration.
arm group label: Budesonide 1MR then 5MR
arm group type: Other
description: All participants will administer budesonide daily via Mucosal Atomization Device (MAD) with a minimum requirement of at least five days a week for the duration of the study in this arm.
st time period: Patients will undergo a 2 week "washout" period. The "washout" period will involve standard of care daily non-medicated intranasal saline irrigation.
nd time period: 1MR administration method once daily for 8 weeks in duration.
rd time period: Patients will undergo a 2 week "washout" period of daily. The "washout" period will involve standard of care daily non-medicated intranasal saline irrigation.
th time period: 5MR administration method once daily for 8 weeks in duration.
intervention type: Drug
intervention name: Budesonide
description: Budesonide is a corticosteroid that is commonly used intranasally to treat CRS.
arm group label: Budesonide 1MR then 5MR
arm group label: Budesonide 5MR then 1MR
other name: Pulmicort
intervention type: Device
intervention name: Mucosal Atomization Device
description: MAD is a device used as an addition to a syringe to atomize medication to increase area of distribution. It is used to administer budesonide within the nasal passages and sinuses to administer medication for CRS.
arm group label: Budesonide 1MR then 5MR
arm group label: Budesonide 5MR then 1MR
intervention type: Device
intervention name: NeilMed squeeze bottle for Impregnated Nasal Saline Irrigation
description: INSI is delivered using a NeilMed squeeze bottle. It is used to administer budesonide within the nasal passages and sinuses to administer medication for CRS.
arm group label: Budesonide 1MR then 5MR
arm group label: Budesonide 5MR then 1MR
other name: INSI
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Amin JAver, MD
role: Principal Investigator
affiliation: The University of British Columbia and St. Paul's Sinus Centre
responsible party type: Principal Investigator
investigator affiliation: St. Paul's Hospital, Canada
investigator full name: Amin Javer
investigator title: Assistant Clinical Professor
mesh term: Sinusitis
mesh term: Chronic Disease
mesh term: Budesonide
sharing ipd: No
ipd description: We will publish final outcomes as scientific paper.