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

Helse Stavanger HF

Status and phase: Enrolling; Phase 4

Conditions: Protracted Bacterial Bronchitis

Treatments: Drug: Amoxicillin-Clavulanate 400 Mg-57 Mg/5 mL Oral Powder for Reconstitution; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT06020716

AMIC 2023

2022-500586-27-00 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 350 estimated patients

Sex: All

Ages: 9 to 36 months old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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350 participants in 4 patient groups, including a placebo group

AMIC 1: Arm A

Experimental group

Description:

In AMIC 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. AMIC 1 Arm A will receive 14 days amoxicillin-clavulanate syrup.

Treatment:

Drug: Amoxicillin-Clavulanate 400 Mg-57 Mg/5 mL Oral Powder for Reconstitution

AMIC 1: Arm B

Placebo Comparator group

Description:

In AMIC 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. AMIC 1 Arm B will receive 14 days placebo syrup.

Treatment:

Drug: Placebo

AMIC 2: Arm C

Experimental group

Description:

In AMIC 2, 210 children will be randomly assigned 1:1 to receive either 14 or 28 days with amoxicillin-clavulanate syrup (arm C and D). AMIC 2 Arm C will receive 14 days amoxicillin-clavulanate syrup and 14 days placebo.

Treatment:

Drug: Placebo

Drug: Amoxicillin-Clavulanate 400 Mg-57 Mg/5 mL Oral Powder for Reconstitution

AMIC 2: Arm D

Experimental group

Description:

In AMIC 2, 210 children will be randomly assigned 1:1 to receive either 14 or 28 days with amoxicillin-clavulanate syrup (arm C and D). AMIC 2 Arm D will receive 28 days amoxicillin-clavulanate syrup.

Treatment:

Drug: Amoxicillin-Clavulanate 400 Mg-57 Mg/5 mL Oral Powder for Reconstitution