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

ClinicalTrials.gov ID

NCT06020716

Lead Sponsor

Helse Stavanger HFOTHER_GOV

Overall Status

Recruiting

Study Type

Interventional

Phase

Phase 4

Enrollment

350Estimated

Last Update Posted

Dec 27, 2024Actual

Start Date

Aug 16, 2023Actual

Primary Completion Date

Apr 30, 2028Estimated

Completion Date

Apr 30, 2028Estimated

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.

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.

• Protracted Bacterial Bronchitis

• Amoxicillin-Clavulanate 400 Mg-57 Mg/5 mL Oral Powder for Reconstitution
• Placebo

Ages Eligible for Study

Child (0-17)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

Yes

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 Purpose

Treatment

Allocation

Randomized

Interventional Model

Parallel Assignment

Masking

Quadruple

Lead Sponsor

Helse Stavanger HFOTHER_GOV

Collaborators

Oslo University HospitalOTHER

Haukeland University HospitalOTHER

Alesund HospitalOTHER

University Hospital, AkershusOTHER

Trondheim University HospitalOTHER

University Hospital of North NorwayOTHER

asle.hirth@helse-bergen.no

Christopher.Stephen.Inchley@ahus.no

uxskjh@ous-hf.no

miib@sus.no+4790203676

Claus.Klingenberg@unn.no

henrik.dollner@ntnu.no

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