<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/NCT03243565</url>
  </required_header>
  <id_info>
    <org_study_id>17-AKD-2</org_study_id>
    <nct_id>NCT03243565</nct_id>
  </id_info>
  <brief_title>Effect of OM-85 on Respiratory Tract Infections and Adenoid Tissue in Children With Adenoid Hypertrophy</brief_title>
  <official_title>Effect of Vaxoral® (OM-85) on Frequency of Respiratory Tract Infections and Size of Adenoid Tissue in Preschool Children With Adenoid Hypertrophy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dr. Sami Ulus Children's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Dr. Sami Ulus Children's 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>
      Clinical research question: Can OM-85 reduce the recurrence of respiratory tract infections&#xD;
      (RTIs) in children with AH by stimulating the immunological response of the host and&#xD;
      therefore, as a consequence reduce the size of adenoid tissue in children with adenoid&#xD;
      hypertrophy? Can this prevent further complications such as surgery need? Half of&#xD;
      participants will receive OM-85, while other half will receive a placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      OM-85 significantly reduces RTIs in children. This effect was proved by many clinical studies&#xD;
      and meta-analyses. A Cochrane meta-analysis first published in 2006 and updated recently&#xD;
      (Del-Rio-Navarro 2012) showed that immunostimulants (IS) could reduce acute RTIs (ARTIs) by&#xD;
      almost 39% when compared to placebo. Among the different IS, OM-85 showed the most robust&#xD;
      evidence with 4 trials of &quot;A quality&quot; according to the Cochrane grading criteria. Pooling six&#xD;
      OM-85 studies, the Cochrane review reported a mean number of ARTIs reduction by -1.20 [95%&#xD;
      Confidence Interval (CI): -1.75, -0.66 ] and a percentage difference in ARTIs by -35.9% [95%&#xD;
      CI: -49.46, -22.35 ] compared to placebo.&#xD;
&#xD;
      Adenoid hypertrophy (AH) is one of the most important respiratory disease in preschool&#xD;
      children. In normal conditions adenoid tissue enlarges up to 5 years and become smaller&#xD;
      afterwards. But in some children who have recurrent upper respiratory tract infections&#xD;
      (URTI)s, it keeps growing and this can be associated with complications. AH may cause&#xD;
      recurrent respiratory infections and each infection contribute to enlargement of adenoid&#xD;
      tissue thus promoting a vicious cycle. Additionally enlarged adenoids are known to be&#xD;
      reservoir for microbes and cause of recurrent or long lasting RTIs.&#xD;
&#xD;
      AH is associated with chronic cough, recurrent and chronic sinusitis, recurrent tonsillitis,&#xD;
      recurrent otitis media with effusion, recurrent other respiratory problems such as, nasal&#xD;
      obstruction and sleep disturbances, sleep apneas. Eventually, AH causes loss of appetite and&#xD;
      growth delay; it is often associated with misusing or over use of antibiotics and often&#xD;
      eventually requires surgery. It decreases quality of life both in children and parents and it&#xD;
      represents a burden not only for families but also for health care system and society due to&#xD;
      increased health cost4.&#xD;
&#xD;
      In one study which investigated the structural and immunological aspects of tonsils and&#xD;
      adenoids of 105 children (54 males and 51 females, aged between 4 and 18 years) who were&#xD;
      affected by chronic inflammatory hypertrophy of palatine tonsils and adenoids which had not&#xD;
      responded to previous medical treatments and who underwent adenotonsillectomy because of&#xD;
      recurrent inflammatory episodes with fever, it was demonstrated that deficit in the&#xD;
      activa-tion of the immune system could be represented by the small quan-tity of messenger&#xD;
      ribonucleic acid (mRNA)s for interleukin-2 (IL-2) and interleukin-4 (IL-4) detected in our&#xD;
      population, suggesting a defective activation of Th1 and Th2 lymphocytes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">November 1, 2017</start_date>
  <completion_date type="Anticipated">May 1, 2019</completion_date>
  <primary_completion_date type="Anticipated">May 1, 2019</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>Parallel Assignment</intervention_model>
    <intervention_model_description>A randomised, double-blind, placebo-controlled, parallel group, phase IV study. First group will receive OM-85 (first 10 day consecutive 3 months; standard treatment regimen) Second group will receive matching placebo at the same posology (first 10 day consecutive 3 months).&#xD;
A second cure of treatment will be given 6 months after inclusion. Patients will be recruited from 01 August 2017 to 01 February 2018. The trial will begin in August 2017 and will be completed in February 2019.&#xD;
By this way every patient will be studied over all seasons (1 year study) .</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Randomization will be done by throwing the coin. Family of patients and doctor (Coordinator / Responsible Investigator Serap Ozmen and Associate Investigator Soner Sahin) will be blind; Researcher Ilknur Bostanci and assistant researcher Gulay Senel will appoint drugs and placebo.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Reduction of number of respiratory tract infections (RTIs)</measure>
    <time_frame>within 12 months</time_frame>
    <description>number of respiratory tract infections (RTIs) such as adenoiditis, sinusitis, tonsillitis, otitis, bronchitis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Reduction in duration of RTIs</measure>
    <time_frame>within 12 months</time_frame>
    <description>duration of RTIs (day)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction of antibiotic use</measure>
    <time_frame>within 12 months</time_frame>
    <description>number of antibiotic use</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction of missed school days</measure>
    <time_frame>within 12 months</time_frame>
    <description>missed school days (day)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction of surgery need</measure>
    <time_frame>within 12 months</time_frame>
    <description>Whether or not surgery (adenoidectomy)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adenoid and tonsil survey</measure>
    <time_frame>within 12 months</time_frame>
    <description>before and after the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Size of adenoid tissue over the 12 months according to radiographic and flexible nasopharyngoscopic evaluation</measure>
    <time_frame>1 year</time_frame>
    <description>The data will be recorded as a perceived percent obstruction of the choana by the adenoid pad, as seen through the endoscope; Lateral neck radiographs will taken and interpreted by the method of Cohen and Konak by a blinded radiologist (Cohen D, Konak S. The evaluation of radiographs of the nasopharynx. Clin Otolaryngol 1985; 10: 73-8.)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">68</enrollment>
  <condition>Adenoid Hypertrophy</condition>
  <condition>Adenoid Hyperplasia</condition>
  <condition>Respiratory Tract Infections</condition>
  <condition>Preschool Children</condition>
  <arm_group>
    <arm_group_label>OM-85</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>OM-85 by mouth (3.5 mg once per day, first 10 days, consecutive 3 months; 10-10-10 days, standard treatment regimen) A second cure of treatment will be given 6 months after inclusion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo by mouth (Pregelatinized starch (Starch 1500)+Mannitol+Magnesium stearate+Anhydrous propyl gallate+Sodium glutamate) the same posology (3.5 mg once per day, first 10 days for consecutive 3 months) A second cure of treatment will be given 6 months after inclusion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>OM-85</intervention_name>
    <description>OM-85 is an oral bacterial lysate of 21 different strains of 8 species and sub-species of the most common respiratory tract pathogens.</description>
    <arm_group_label>OM-85</arm_group_label>
    <other_name>Vaxoral</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Pregelatinized starch (Starch 1500)+Mannitol+Magnesium stearate+Anhydrous propyl gallate+Sodium glutamate</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Children (age: 2-6 years)&#xD;
&#xD;
          -  Who experienced recurrent RTIs (at least 3 episodes in 6 months before the inclusion)&#xD;
&#xD;
          -  Who have symptoms of AH (snoring; mouth breathing awake; mouth breathing asleep; nasal&#xD;
             congestion; hyponasal voice; chronic nasal discharge; daytime drowsiness, or&#xD;
             hyperactivity; restless sleep; sleep apnoea &lt;15 sec; night cough; and poor oral&#xD;
             intake/weight loss) based on the symptoms score questionnaire&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Atopy&#xD;
&#xD;
          -  Gastroesophageal reflux&#xD;
&#xD;
          -  Immune deficiency&#xD;
&#xD;
          -  Asthma or allergic rhinitis&#xD;
&#xD;
          -  Premature delivery&#xD;
&#xD;
          -  Anatomic alterations of the respiratory tract; chronic respiratory diseases&#xD;
             (tuberculosis and cystic fibrosis); autoimmune disease; liver&#xD;
&#xD;
          -  Kidney failure; malnutrition; cancer&#xD;
&#xD;
          -  Treatment with inhaled or systemic corticosteroids within the previous month&#xD;
&#xD;
          -  Treatment with immunosuppressants, immunostimulants, gamma globulins, or&#xD;
             anticonvulsive drugs within the previous 6 months.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>6 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Serap Ozmen</last_name>
    <role>Study Chair</role>
    <affiliation>Health of Science University, Dr Sami Ulus Maternity and Children Research and Training Hospital, Ankara, TURKEY</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Serap Ozmen, MD</last_name>
    <phone>+903123056250</phone>
    <email>serapozmen@yahoo.com</email>
  </overall_contact>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>July 26, 2017</study_first_submitted>
  <study_first_submitted_qc>August 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 9, 2017</study_first_posted>
  <last_update_submitted>October 4, 2017</last_update_submitted>
  <last_update_submitted_qc>October 4, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dr. Sami Ulus Children's Hospital</investigator_affiliation>
    <investigator_full_name>Serap Ozmen</investigator_full_name>
    <investigator_title>MD, Pediatric Allergist and Assoc. Prof of Pediatrics</investigator_title>
  </responsible_party>
  <keyword>adenoid hypertrophy</keyword>
  <keyword>Adenoid Hyperplasia</keyword>
  <keyword>children</keyword>
  <keyword>respiratory tract infection</keyword>
  <keyword>adenotonsillectomy</keyword>
  <keyword>OM-85</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Respiratory Tract Infections</mesh_term>
    <mesh_term>Hyperplasia</mesh_term>
    <mesh_term>Hypertrophy</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan: SAP OM85adenoid</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 23, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT03243565/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form: ICF OM85adenoid</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 23, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT03243565/ICF_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol: SP OM85adenoid</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 23, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT03243565/Prot_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form: SUM OM85adenoid</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 23, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/65/NCT03243565/Prot_SAP_ICF_003.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03243565
org study id: 17-AKD-2
nct id: NCT03243565
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Clinical research question: Can OM-85 reduce the recurrence of respiratory tract infections
      (RTIs) in children with AH by stimulating the immunological response of the host and
      therefore, as a consequence reduce the size of adenoid tissue in children with adenoid
      hypertrophy? Can this prevent further complications such as surgery need? Half of
      participants will receive OM-85, while other half will receive a placebo.
OM-85 significantly reduces RTIs in children. This effect was proved by many clinical studies
      and meta-analyses. A Cochrane meta-analysis first published in 2006 and updated recently
      (Del-Rio-Navarro 2012) showed that immunostimulants (IS) could reduce acute RTIs (ARTIs) by
      almost 39% when compared to placebo. Among the different IS, OM-85 showed the most robust
      evidence with 4 trials of "A quality" according to the Cochrane grading criteria. Pooling six
      OM-85 studies, the Cochrane review reported a mean number of ARTIs reduction by -1.20 [95%
      Confidence Interval (CI): -1.75, -0.66 ] and a percentage difference in ARTIs by -35.9% [95%
      CI: -49.46, -22.35 ] compared to placebo.

      Adenoid hypertrophy (AH) is one of the most important respiratory disease in preschool
      children. In normal conditions adenoid tissue enlarges up to 5 years and become smaller
      afterwards. But in some children who have recurrent upper respiratory tract infections
      (URTI)s, it keeps growing and this can be associated with complications. AH may cause
      recurrent respiratory infections and each infection contribute to enlargement of adenoid
      tissue thus promoting a vicious cycle. Additionally enlarged adenoids are known to be
      reservoir for microbes and cause of recurrent or long lasting RTIs.

      AH is associated with chronic cough, recurrent and chronic sinusitis, recurrent tonsillitis,
      recurrent otitis media with effusion, recurrent other respiratory problems such as, nasal
      obstruction and sleep disturbances, sleep apneas. Eventually, AH causes loss of appetite and
      growth delay; it is often associated with misusing or over use of antibiotics and often
      eventually requires surgery. It decreases quality of life both in children and parents and it
      represents a burden not only for families but also for health care system and society due to
      increased health cost4.

      In one study which investigated the structural and immunological aspects of tonsils and
      adenoids of 105 children (54 males and 51 females, aged between 4 and 18 years) who were
      affected by chronic inflammatory hypertrophy of palatine tonsils and adenoids which had not
      responded to previous medical treatments and who underwent adenotonsillectomy because of
      recurrent inflammatory episodes with fever, it was demonstrated that deficit in the
      activa-tion of the immune system could be represented by the small quan-tity of messenger
      ribonucleic acid (mRNA)s for interleukin-2 (IL-2) and interleukin-4 (IL-4) detected in our
      population, suggesting a defective activation of Th1 and Th2 lymphocytes.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A randomised, double-blind, placebo-controlled, parallel group, phase IV study. First group will receive OM-85 (first 10 day consecutive 3 months; standard treatment regimen) Second group will receive matching placebo at the same posology (first 10 day consecutive 3 months).
A second cure of treatment will be given 6 months after inclusion. Patients will be recruited from 01 August 2017 to 01 February 2018. The trial will begin in August 2017 and will be completed in February 2019.
By this way every patient will be studied over all seasons (1 year study) .
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Randomization will be done by throwing the coin. Family of patients and doctor (Coordinator / Responsible Investigator Serap Ozmen and Associate Investigator Soner Sahin) will be blind; Researcher Ilknur Bostanci and assistant researcher Gulay Senel will appoint drugs and placebo.
measure: Reduction of number of respiratory tract infections (RTIs)
time frame: within 12 months
description: number of respiratory tract infections (RTIs) such as adenoiditis, sinusitis, tonsillitis, otitis, bronchitis
measure: Reduction in duration of RTIs
time frame: within 12 months
description: duration of RTIs (day)
measure: Reduction of antibiotic use
time frame: within 12 months
description: number of antibiotic use
measure: Reduction of missed school days
time frame: within 12 months
description: missed school days (day)
measure: Reduction of surgery need
time frame: within 12 months
description: Whether or not surgery (adenoidectomy)
measure: Adenoid and tonsil survey
time frame: within 12 months
description: before and after the study
measure: Size of adenoid tissue over the 12 months according to radiographic and flexible nasopharyngoscopic evaluation
time frame: 1 year
description: The data will be recorded as a perceived percent obstruction of the choana by the adenoid pad, as seen through the endoscope; Lateral neck radiographs will taken and interpreted by the method of Cohen and Konak by a blinded radiologist (Cohen D, Konak S. The evaluation of radiographs of the nasopharynx. Clin Otolaryngol 1985; 10: 73-8.)
arm group label: OM-85
arm group type: Active Comparator
description: OM-85 by mouth (3.5 mg once per day, first 10 days, consecutive 3 months; 10-10-10 days, standard treatment regimen) A second cure of treatment will be given 6 months after inclusion.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo by mouth (Pregelatinized starch (Starch 1500)+Mannitol+Magnesium stearate+Anhydrous propyl gallate+Sodium glutamate) the same posology (3.5 mg once per day, first 10 days for consecutive 3 months) A second cure of treatment will be given 6 months after inclusion.
intervention type: Biological
intervention name: OM-85
description: OM-85 is an oral bacterial lysate of 21 different strains of 8 species and sub-species of the most common respiratory tract pathogens.
arm group label: OM-85
other name: Vaxoral
intervention type: Biological
intervention name: Placebo
description: Pregelatinized starch (Starch 1500)+Mannitol+Magnesium stearate+Anhydrous propyl gallate+Sodium glutamate
arm group label: Placebo
criteria: 
gender: All
minimum age: 2 Years
maximum age: 6 Years
healthy volunteers: No
last name: Serap Ozmen
role: Study Chair
affiliation: Health of Science University, Dr Sami Ulus Maternity and Children Research and Training Hospital, Ankara, TURKEY
last name: Serap Ozmen, MD
phone: +903123056250
email: serapozmen@yahoo.com
responsible party type: Principal Investigator
investigator affiliation: Dr. Sami Ulus Children's Hospital
investigator full name: Serap Ozmen
investigator title: MD, Pediatric Allergist and Assoc. Prof of Pediatrics
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Respiratory Tract Infections
mesh term: Hyperplasia
mesh term: Hypertrophy
sharing ipd: No
provided document: 
provided document: 
provided document: 
provided document: 