xml: <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/NCT06020716</url>
    </required_header>
    <id_info>
      <org_study_id>AMIC 2023</org_study_id>
      <secondary_id>2022-500586-27-00</secondary_id>
      <nct_id>NCT06020716</nct_id>
    </id_info>
    <brief_title>Antibiotics, Microbiology and Immunology in Children With Chronic Wet Couch - the AMIC Study</brief_title>
    <acronym>AMIC</acronym>
    <official_title>A Phase 4 Double Blinded Study With Two Different Interventions, Each With Two Arms, to Evaluate the Clinical Efficacy of Antibiotics and the Role of Microbiology, Immunology and Genetics in Children Aged 9-36 Months With Chronic Wet Cough.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Helse Stavanger HF</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Oslo University Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Haukeland University Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Alesund Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Helse Nord</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
      <collaborator>
        <agency>St. Olavs Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>University Hospital, Akershus</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Helse Stavanger HF</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>Yes</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 AMIC study is a double-blind, placebo-controlled, multicenter, nationwide, randomized&#xD;
        controlled academic pharmaceutical trial.&#xD;
  &#xD;
        OVERALL PRIMARY OBJECTIVES:&#xD;
  &#xD;
          -  To study the clinical efficacy of antibiotics in children with chronic wet cough (CWC).&#xD;
  &#xD;
          -  To study if duration of treatment with antibiotics in children with CWC has impact on&#xD;
             efficacy or time to relapse of symptoms.&#xD;
  &#xD;
        OVERALL SECONDARY OBJECTIVE:&#xD;
  &#xD;
        -To study respiratory pathogens and the diversity/composition of airway and gut microbiome in&#xD;
        children with CWC compared to healthy controls, and changes in pathogens/microbiome after&#xD;
        treatment with antibiotics.&#xD;
  &#xD;
        OVERALL TERTIARY OBJECTIVE:&#xD;
  &#xD;
        -To study inflammatory markers in children with CWC and the impact of treatment with&#xD;
        antibiotics. Furthermore, identify children with CWC who have primary immunodeficiency (PID)&#xD;
        based on functional laboratory markers and genetic markers of PID.&#xD;
  &#xD;
        The study will include two different interventions:&#xD;
  &#xD;
        INTERVENTION 1:&#xD;
  &#xD;
        Participants will be randomly assigned to 14 days antibiotics or placebo&#xD;
  &#xD;
        INTERVENTION 2:&#xD;
  &#xD;
        Participants will be randomly assigned 1:1 to receive either 14 or 28 days with&#xD;
        amoxicillin-clavulanate syrup&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Study populations:&#xD;
  &#xD;
        INTERVENTION 1:&#xD;
  &#xD;
        90 children with chronic wet cough aged 9-36 months&#xD;
  &#xD;
        INTERVENTION 2:&#xD;
  &#xD;
        210 children with chronic wet cough aged 9-26 months&#xD;
  &#xD;
        Both intervention groups will be followed until 24 months after the start of the RCT.&#xD;
  &#xD;
        HEALTHY CONTROL GROUP:&#xD;
  &#xD;
        To study the role of respiratory pathogens, airway and gut microbiome, inflammatory markers&#xD;
        and immunodeficiency, 50 healthy controls will be included for comparison to IV 1. The&#xD;
        healthy controls will be followed for 6 months after inclusion.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 16, 2023</start_date>
    <completion_date type="Anticipated">April 30, 2028</completion_date>
    <primary_completion_date type="Anticipated">April 30, 2028</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>This is a Phase 4, randomized controlled, parallel group, multicenter, double blind study of amoxicillin-clavulanate in children 9-36 months of age with chronic wet cough. A total of 300 children will be included in the study in two different Intervention groups. Intervention 1 will be performed before Intervention 2.There is no randomization between IV 1 and IV 2.&#xD;
  To study the role of respiratory pathogens, microbiome and inflammation, 50 healthy controls will be included for comparison to IV 1.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Response to treatment</measure>
      <time_frame>Response to treatment will be assessed 14 days after end of antibiotic treatment</time_frame>
      <description>Response to treatment is defined as an improvement in baseline validated Verbal category descriptive (VCD) cough score ≤2 at the end of treatment or cessation of coughing for a minimum period of 3 days within the treatment period.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Relapse of symptoms</measure>
      <time_frame>Relapse of symptoms will be assesed up to 24 months after end of antibiotic treatment</time_frame>
      <description>Relapse of symptoms after antibiotic treatment for chronic wet cough is defined as a new period of wet cough - after a period of at least 7 days without symptoms - lasting for more than four weeks, or an episode of wet cough of at least two weeks duration which was treated with antibiotics by the child's general practitioner or treating physician. The start of relapse is the first day of cough of such a period or episode.</description>
    </secondary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">350</enrollment>
    <condition>Protracted Bacterial Bronchitis</condition>
    <arm_group>
      <arm_group_label>Intervention group 1 (IV 1) Arm A</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>In the first Intervention group (IV 1), 90 children will be randomly be assigned 1:1 to receive either amoxicillin-clavulanate syrup or placebo (Arm A and B) for 14 days. IV 1 Arm A will receive 14 days amoxicillin-clavulanate syrup..</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Intervention group 1 (IV 1) Arm B</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>In the first Intervention group (IV 1), 90 children will be randomly be assigned 1:1 to receive either amoxicillin-clavulanate syrup or placebo (arm A and B) for 14 days. IV 1 Arm B will receive 14 days placebo syrup.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Intervention group 2 (IV2) Arm C</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>In the second intervention group (IV 2), 210 children will be randomly assigned 1:1 to receive either 14 or 28 days with amoxicillin-clavulanate syrup (arm C and D). IV 2 Arm C will receive 14 days amoxicillin-clavulanate syrup and 14 days placebo.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Intervention group 2 (IV 2) Arm D</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>In the second intervention group (IV 2), 210 children will be randomly assigned 1:1 to receive either 14 or 28 days with amoxicillin-clavulanate syrup (arm C and D). IV 2 Arm D will receive 28 days amoxicillin-clavulanate syrup.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Amoxicillin-Clavulanate 400 Mg-57 Mg/5 mL Oral Powder for Reconstitution</intervention_name>
      <description>Three times daily</description>
      <arm_group_label>Intervention group 1 (IV 1) Arm A</arm_group_label>
      <arm_group_label>Intervention group 2 (IV 2) Arm D</arm_group_label>
      <arm_group_label>Intervention group 2 (IV2) Arm C</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Three times daily</description>
      <arm_group_label>Intervention group 1 (IV 1) Arm B</arm_group_label>
      <arm_group_label>Intervention group 2 (IV2) Arm C</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age &gt; 9 and younger than 36 months.&#xD;
  &#xD;
            2. Body weight &gt; 7 kg and &lt; 24 kg.&#xD;
  &#xD;
            3. Born term with Gestational age &gt; 37 weeks.&#xD;
  &#xD;
            4. Chronic wet cough for &gt; 4 weeks at screening and in addition average cough score last&#xD;
               7 days at randomization ≥ 4 points and without signs of another cause.&#xD;
  &#xD;
            5. Written informed consent obtained from both parents at inclusion.&#xD;
  &#xD;
            6. The study subject must be assessed as eligble for treatment with Augmentin.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Gestational age &lt; 37 weeks.&#xD;
  &#xD;
            2. History of acute upper or lower airway infection the last 4 weeks.&#xD;
  &#xD;
            3. History of other viral or bacterial infections the last 2 weeks.&#xD;
  &#xD;
            4. Episode with temperature above 38 °C during the last 2 weeks.&#xD;
  &#xD;
            5. Previous diagnosed with chronic lung disease such as cystic fibrosis, primary ciliary&#xD;
               dyskinesia, interstitial lung disease, asthma, immunodeficiency, esophagus atresia.&#xD;
  &#xD;
            6. Cardiac disease, except persisting foramen ovale or ductus arteriosus.&#xD;
  &#xD;
            7. Severe feeding problems/aspiration.&#xD;
  &#xD;
            8. Gastroesophageal reflux suspicion or confirmed by ph measurement.&#xD;
  &#xD;
            9. Suspicion of hypertrophic tonsils or adenoids&#xD;
  &#xD;
           10. Episodes of bronchopulmonary obstruction suggesting asthma&#xD;
  &#xD;
           11. Presence of gross neurodevelopmental delay, or suspicion of neurological disease.&#xD;
  &#xD;
           12. History of known or suspected allergic reactions to amoxicillin-clavulanate or any&#xD;
               other betalactam.&#xD;
  &#xD;
           13. Episodes with haemoptysis and with unknown cause.&#xD;
  &#xD;
           14. Radiographic changes other than perihilar changes confirmed by x-ray at screening.&#xD;
  &#xD;
           15. At examination: Digital clubbing, hypoxia, chest wall deformity, dyspnoea at rest.&#xD;
  &#xD;
           16. Parents unable to speak and/or understand Norwegian language.&#xD;
  &#xD;
           17. Received systemic antibiotics within the last 6 months before inclusion.&#xD;
  &#xD;
           18. Participation in another trial.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>9 Months</minimum_age>
      <maximum_age>36 Months</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Knut Øymar, MD PhD</last_name>
      <role>Study Chair</role>
      <affiliation>Stavanger University Hospital, Norway</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Knut Øymar, MD PhD</last_name>
      <phone>+47 41633426</phone>
      <email>knut.oymar@sus.no</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Ingvild B Mikalsen, MD PhD</last_name>
      <phone>+47 46892206</phone>
      <email>ingvild.bruun.mikalsen@sus.no</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Stavanger University Hospital</name>
        <address>
          <city>Stavanger</city>
          <zip>40</zip>
          <country>Norway</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Ingvild Bruun Mikalsen, Ass.Prof</last_name>
        <phone>+4790203676</phone>
        <email>miib@sus.no</email>
      </contact>
      <contact_backup>
        <last_name>Knut Øymar, Prof</last_name>
        <phone>+4741633426</phone>
        <email>knut.oymar@sus.no</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>Norway</country>
    </location_countries>
    <verification_date>April 2023</verification_date>
    <study_first_submitted>July 3, 2023</study_first_submitted>
    <study_first_submitted_qc>August 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 1, 2023</study_first_posted>
    <last_update_submitted>August 28, 2023</last_update_submitted>
    <last_update_submitted_qc>August 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Chronic wet cough</keyword>
    <keyword>Antibiotic</keyword>
    <keyword>Children</keyword>
    <keyword>Microbiology</keyword>
    <keyword>Immunology</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Bronchitis</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Amoxicillin</mesh_term>
      <mesh_term>Clavulanic Acid</mesh_term>
      <mesh_term>Clavulanic Acids</mesh_term>
      <mesh_term>Amoxicillin-Potassium Clavulanate Combination</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06020716
  org study id: AMIC 2023
  secondary id: 2022-500586-27-00
  nct id: NCT06020716
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: Yes
  The AMIC study is a double-blind, placebo-controlled, multicenter, nationwide, randomized
        controlled academic pharmaceutical trial.
  
        OVERALL PRIMARY OBJECTIVES:
  
          -  To study the clinical efficacy of antibiotics in children with chronic wet cough (CWC).
  
          -  To study if duration of treatment with antibiotics in children with CWC has impact on
             efficacy or time to relapse of symptoms.
  
        OVERALL SECONDARY OBJECTIVE:
  
        -To study respiratory pathogens and the diversity/composition of airway and gut microbiome in
        children with CWC compared to healthy controls, and changes in pathogens/microbiome after
        treatment with antibiotics.
  
        OVERALL TERTIARY OBJECTIVE:
  
        -To study inflammatory markers in children with CWC and the impact of treatment with
        antibiotics. Furthermore, identify children with CWC who have primary immunodeficiency (PID)
        based on functional laboratory markers and genetic markers of PID.
  
        The study will include two different interventions:
  
        INTERVENTION 1:
  
        Participants will be randomly assigned to 14 days antibiotics or placebo
  
        INTERVENTION 2:
  
        Participants will be randomly assigned 1:1 to receive either 14 or 28 days with
        amoxicillin-clavulanate syrup
  Study populations:
  
        INTERVENTION 1:
  
        90 children with chronic wet cough aged 9-36 months
  
        INTERVENTION 2:
  
        210 children with chronic wet cough aged 9-26 months
  
        Both intervention groups will be followed until 24 months after the start of the RCT.
  
        HEALTHY CONTROL GROUP:
  
        To study the role of respiratory pathogens, airway and gut microbiome, inflammatory markers
        and immunodeficiency, 50 healthy controls will be included for comparison to IV 1. The
        healthy controls will be followed for 6 months after inclusion.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: This is a Phase 4, randomized controlled, parallel group, multicenter, double blind study of amoxicillin-clavulanate in children 9-36 months of age with chronic wet cough. A total of 300 children will be included in the study in two different Intervention groups. Intervention 1 will be performed before Intervention 2.There is no randomization between IV 1 and IV 2.
  To study the role of respiratory pathogens, microbiome and inflammation, 50 healthy controls will be included for comparison to IV 1.
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Response to treatment
  time frame: Response to treatment will be assessed 14 days after end of antibiotic treatment
  description: Response to treatment is defined as an improvement in baseline validated Verbal category descriptive (VCD) cough score ≤2 at the end of treatment or cessation of coughing for a minimum period of 3 days within the treatment period.
  measure: Relapse of symptoms
  time frame: Relapse of symptoms will be assesed up to 24 months after end of antibiotic treatment
  description: Relapse of symptoms after antibiotic treatment for chronic wet cough is defined as a new period of wet cough - after a period of at least 7 days without symptoms - lasting for more than four weeks, or an episode of wet cough of at least two weeks duration which was treated with antibiotics by the child's general practitioner or treating physician. The start of relapse is the first day of cough of such a period or episode.
  arm group label: Intervention group 1 (IV 1) Arm A
  arm group type: Experimental
  description: In the first Intervention group (IV 1), 90 children will be randomly be assigned 1:1 to receive either amoxicillin-clavulanate syrup or placebo (Arm A and B) for 14 days. IV 1 Arm A will receive 14 days amoxicillin-clavulanate syrup..
  arm group label: Intervention group 1 (IV 1) Arm B
  arm group type: Placebo Comparator
  description: In the first Intervention group (IV 1), 90 children will be randomly be assigned 1:1 to receive either amoxicillin-clavulanate syrup or placebo (arm A and B) for 14 days. IV 1 Arm B will receive 14 days placebo syrup.
  arm group label: Intervention group 2 (IV2) Arm C
  arm group type: Experimental
  description: In the second intervention group (IV 2), 210 children will be randomly assigned 1:1 to receive either 14 or 28 days with amoxicillin-clavulanate syrup (arm C and D). IV 2 Arm C will receive 14 days amoxicillin-clavulanate syrup and 14 days placebo.
  arm group label: Intervention group 2 (IV 2) Arm D
  arm group type: Experimental
  description: In the second intervention group (IV 2), 210 children will be randomly assigned 1:1 to receive either 14 or 28 days with amoxicillin-clavulanate syrup (arm C and D). IV 2 Arm D will receive 28 days amoxicillin-clavulanate syrup.
  intervention type: Drug
  intervention name: Amoxicillin-Clavulanate 400 Mg-57 Mg/5 mL Oral Powder for Reconstitution
  description: Three times daily
  arm group label: Intervention group 1 (IV 1) Arm A
  arm group label: Intervention group 2 (IV 2) Arm D
  arm group label: Intervention group 2 (IV2) Arm C
  intervention type: Drug
  intervention name: Placebo
  description: Three times daily
  arm group label: Intervention group 1 (IV 1) Arm B
  arm group label: Intervention group 2 (IV2) Arm C
  criteria: 
  gender: All
  minimum age: 9 Months
  maximum age: 36 Months
  healthy volunteers: Accepts Healthy Volunteers
  last name: Knut Øymar, MD PhD
  role: Study Chair
  affiliation: Stavanger University Hospital, Norway
  last name: Knut Øymar, MD PhD
  phone: +47 41633426
  email: knut.oymar@sus.no
  last name: Ingvild B Mikalsen, MD PhD
  phone: +47 46892206
  email: ingvild.bruun.mikalsen@sus.no
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  country: Norway
  responsible party type: Sponsor
  mesh term: Bronchitis
  mesh term: Amoxicillin
  mesh term: Clavulanic Acid
  mesh term: Clavulanic Acids
  mesh term: Amoxicillin-Potassium Clavulanate Combination
  sharing ipd: No