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Antibiotics, Microbiology and Immunology in Children With Chronic Wet Couch - the AMIC Study (AMIC)

Primary Purpose

Protracted Bacterial Bronchitis

Status
Recruiting
Phase
Phase 4
Locations
Norway
Study Type
Interventional
Intervention
Amoxicillin-Clavulanate 400 Mg-57 Mg/5 mL Oral Powder for Reconstitution
Placebo
Sponsored by
Helse Stavanger HF
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Protracted Bacterial Bronchitis focused on measuring Chronic wet cough, Antibiotic, Children, Microbiology, Immunology

Eligibility Criteria

9 Months - 36 Months (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Age > 9 and younger than 36 months. Body weight > 7 kg and < 24 kg. Born term with Gestational age > 37 weeks. Chronic wet cough for > 4 weeks at screening and in addition average cough score last 7 days at randomization ≥ 4 points and without signs of another cause. Written informed consent obtained from both parents at inclusion. The study subject must be assessed as eligble for treatment with Augmentin. Exclusion Criteria: Gestational age < 37 weeks. History of acute upper or lower airway infection the last 4 weeks. History of other viral or bacterial infections the last 2 weeks. Episode with temperature above 38 °C during the last 2 weeks. Previous diagnosed with chronic lung disease such as cystic fibrosis, primary ciliary dyskinesia, interstitial lung disease, asthma, immunodeficiency, esophagus atresia. Cardiac disease, except persisting foramen ovale or ductus arteriosus. Severe feeding problems/aspiration. Gastroesophageal reflux suspicion or confirmed by ph measurement. Suspicion of hypertrophic tonsils or adenoids Episodes of bronchopulmonary obstruction suggesting asthma Presence of gross neurodevelopmental delay, or suspicion of neurological disease. History of known or suspected allergic reactions to amoxicillin-clavulanate or any other betalactam. Episodes with haemoptysis and with unknown cause. Radiographic changes other than perihilar changes confirmed by x-ray at screening. At examination: Digital clubbing, hypoxia, chest wall deformity, dyspnoea at rest. Parents unable to speak and/or understand Norwegian language. Received systemic antibiotics within the last 6 months before inclusion. Participation in another trial.

Sites / Locations

  • Stavanger University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Experimental

Experimental

Arm Label

Intervention group 1 (IV 1) Arm A

Intervention group 1 (IV 1) Arm B

Intervention group 2 (IV2) Arm C

Intervention group 2 (IV 2) Arm D

Arm 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..

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.

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.

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.

Outcomes

Primary Outcome Measures

Response to treatment
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.

Secondary Outcome Measures

Relapse of symptoms
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.

Full Information

First Posted
July 3, 2023
Last Updated
August 28, 2023
Sponsor
Helse Stavanger HF
Collaborators
Oslo University Hospital, Haukeland University Hospital, Alesund Hospital, Helse Nord, St. Olavs Hospital, University Hospital, Akershus
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1. Study Identification

Unique Protocol Identification Number
NCT06020716
Brief Title
Antibiotics, Microbiology and Immunology in Children With Chronic Wet Couch - the AMIC Study
Acronym
AMIC
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.
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 16, 2023 (Actual)
Primary Completion Date
April 30, 2028 (Anticipated)
Study Completion Date
April 30, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Helse Stavanger HF
Collaborators
Oslo University Hospital, Haukeland University Hospital, Alesund Hospital, Helse Nord, St. Olavs Hospital, University Hospital, Akershus

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Protracted Bacterial Bronchitis
Keywords
Chronic wet cough, Antibiotic, Children, Microbiology, Immunology

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
350 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention group 1 (IV 1) Arm A
Arm Type
Experimental
Arm 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 Title
Intervention group 1 (IV 1) Arm B
Arm Type
Placebo Comparator
Arm 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 Title
Intervention group 2 (IV2) Arm C
Arm Type
Experimental
Arm 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 Title
Intervention group 2 (IV 2) Arm D
Arm Type
Experimental
Arm 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(s)
Amoxicillin-Clavulanate 400 Mg-57 Mg/5 mL Oral Powder for Reconstitution
Intervention Description
Three times daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Three times daily
Primary Outcome Measure Information:
Title
Response to 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.
Time Frame
Response to treatment will be assessed 14 days after end of antibiotic treatment
Secondary Outcome Measure Information:
Title
Relapse of symptoms
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.
Time Frame
Relapse of symptoms will be assesed up to 24 months after end of antibiotic treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
9 Months
Maximum Age & Unit of Time
36 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Age > 9 and younger than 36 months. Body weight > 7 kg and < 24 kg. Born term with Gestational age > 37 weeks. Chronic wet cough for > 4 weeks at screening and in addition average cough score last 7 days at randomization ≥ 4 points and without signs of another cause. Written informed consent obtained from both parents at inclusion. The study subject must be assessed as eligble for treatment with Augmentin. Exclusion Criteria: Gestational age < 37 weeks. History of acute upper or lower airway infection the last 4 weeks. History of other viral or bacterial infections the last 2 weeks. Episode with temperature above 38 °C during the last 2 weeks. Previous diagnosed with chronic lung disease such as cystic fibrosis, primary ciliary dyskinesia, interstitial lung disease, asthma, immunodeficiency, esophagus atresia. Cardiac disease, except persisting foramen ovale or ductus arteriosus. Severe feeding problems/aspiration. Gastroesophageal reflux suspicion or confirmed by ph measurement. Suspicion of hypertrophic tonsils or adenoids Episodes of bronchopulmonary obstruction suggesting asthma Presence of gross neurodevelopmental delay, or suspicion of neurological disease. History of known or suspected allergic reactions to amoxicillin-clavulanate or any other betalactam. Episodes with haemoptysis and with unknown cause. Radiographic changes other than perihilar changes confirmed by x-ray at screening. At examination: Digital clubbing, hypoxia, chest wall deformity, dyspnoea at rest. Parents unable to speak and/or understand Norwegian language. Received systemic antibiotics within the last 6 months before inclusion. Participation in another trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Knut Øymar, MD PhD
Phone
+47 41633426
Email
knut.oymar@sus.no
First Name & Middle Initial & Last Name or Official Title & Degree
Ingvild B Mikalsen, MD PhD
Phone
+47 46892206
Email
ingvild.bruun.mikalsen@sus.no
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Knut Øymar, MD PhD
Organizational Affiliation
Stavanger University Hospital, Norway
Official's Role
Study Chair
Facility Information:
Facility Name
Stavanger University Hospital
City
Stavanger
ZIP/Postal Code
40
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ingvild Bruun Mikalsen, Ass.Prof
Phone
+4790203676
Email
miib@sus.no
First Name & Middle Initial & Last Name & Degree
Knut Øymar, Prof
Phone
+4741633426
Email
knut.oymar@sus.no

12. IPD Sharing Statement

Plan to Share IPD
No

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Antibiotics, Microbiology and Immunology in Children With Chronic Wet Couch - the AMIC Study

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