Clinical trial NCT06020716: Antibiotics, Microbiology and Immunology in Children With Chronic Wet Cough - the AMIC Study
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
Overall status: RECRUITING
Phase: PHASE4
Conditions: Protracted Bacterial Bronchitis
Keywords: Chronic wet cough
Antibiotic
Children
Microbiology
Immunology
Lead sponsor: Helse Stavanger HF
Sponsor class: OTHER_GOV
Collaborators: name: Oslo University Hospital
name: Haukeland University Hospital
name: Alesund Hospital
name: University Hospital, Akershus
name: Trondheim University Hospital
name: University Hospital of North Norway
First posted: 2023-09-01
Enrollment: 350
Sex: ALL
Minimum age (years): 9
Maximum age (years): 36
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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 RCTs; AMIC 1 and AMIC 2.AMIC 1 will be performed before AMIC 2.There is no randomization between AMIC 1 and AMIC 2.

To study the role of respiratory pathogens, microbiome and inflammation, 50 healthy controls will be included for comparison.
Primary purpose: TREATMENT

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 the role of inflammation, immunology, and genetics in children with chronic wet cough and suspicion of PBB to increase the knowledge of pathophysiological mechanisms associated with PBB.

The study will include two different RCTs AMIC 1 and AMIC 2:

AMIC 1:

Participants will be randomly assigned to 14 days amoxicillin-clavulanate syrup or placebo.

AMIC 2:

Participants will be randomly assigned 1:1 to receive either 14 or 28 days with amoxicillin-clavulanate syrup.

Detailed description: Study populations:

AMIC 1:

90 children with chronic wet cough aged 9-36 months.

AMIC 2:

210 children with chronic wet cough aged 9-36 months.

All children will be followed until 24 months after the start of the Randomized Controlled Trial (RCT).

HEALTHY CONTROL GROUP:

To study the role of respiratory pathogens, airway and gut microbiome, inflammation and immunology, 50 healthy controls will be included for comparison to AMIC 1. The healthy controls will have a second visit 6 months after inclusion.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 9 and \< 36 months.
2. Body weight ≥ 7 kg and \< 24 kg.
3. Born term with Gestational age ≥ 37 weeks.
4. 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. Registration ≥ 5 days is mandatory.
5. Written informed consent obtained from both parents at inclusion.
6. The study subject must be assessed as eligible for treatment with Augmentin.

Exclusion Criteria:

1. Gestational age \< 37 weeks.
2. History of acute upper or lower airway infection the last 2 weeks.
3. History of other viral or bacterial infections the last 2 weeks.
4. Episode with temperature above 38 °C during the last 2 weeks.
5. Previous diagnosed with chronic lung disease such as cystic fibrosis, primary ciliary dyskinesia, interstitial lung disease, asthma, immunodeficiency, esophagus atresia.
6. Cardiac disease, except persisting foramen ovale or ductus arteriosus.
7. Severe feeding problems/aspiration.
8. Gastroesophageal reflux suspicion or confirmed by ph measurement.
9. Suspicion of hypertrophic tonsils or adenoids
10. Episodes of bronchopulmonary obstruction suggesting asthma
11. Presence of gross neurodevelopmental delay, or suspicion of neurological disease.
12. History of known or suspected allergic reactions to amoxicillin-clavulanate or any other betalactam.
13. Episodes with haemoptysis and with unknown cause.
14. Radiographic changes other than perihilar changes confirmed by x-ray at screening.
15. At examination: Digital clubbing, hypoxia, chest wall deformity, dyspnoea at rest.
16. Parents unable to speak and/or understand Norwegian language.
17. Received systemic antibiotics within the last 6 months before inclusion.
18. Participation in another clinical intervention trial.

Primary outcomes:
measure: Response to treatment
timeFrame: Response to treatment will be assessed 14 days after end of antibiotic treatment
Secondary outcomes:
measure: Relapse of symptoms
timeFrame: Relapse of symptoms will be assessed up to 24 months after end of antibiotic treatment
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Lillestrøm
country: Norway
facility: Akershus University Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Tromsø
country: Norway
facility: University Hospital of North-Norway
city: Trondheim
country: Norway
facility: Trondheim University Hospital
city: Ålesund
country: Norway
facility: Ålesund Hospital
Study officials:
affiliation: Helse Stavanger HF
name: Knut Øymar, MD PhD
role: STUDY_CHAIR
References: