The AMIC study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stavanger University Hospital

Participant type

Pediatric, Healthy volunteers, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

15 Aug 2023 → ongoing

Decision date (initial)

2023-04-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

The overall aims of the AMIC study are to study the clinical efficacy of antibiotics in children with CWC with respect to resolution of symptoms and long-term outcomes as well as the impact of airway and gut microbiome, inflammation and genetics.

1.1 Intervention 1:
Is response to treatment in children with CWC higher in those receiving 14 days treatment with amoxicillin-clavulanate than placebo?
1.2 Intervention 2:
Is the time to relapse of CWC different for those having received 14 days duration of therapy compared to those having received 28 days duration of therapy with amoxicillin-clavulanate?

Secondary objectives 20

1. 1.3 Intervention 2: (IV 2) Is response to treatment different in those receiving 28 days duration of therapy compared to those receiving 14 days duration of therapy with amoxicillin-clavulanate?
2. 1.4 Intervention 2 (IV 2): Is the proportion of relapse of CWC different for those having received 14 days duration of therapy compared to those having received 28 days duration of therapy with amoxicillin-clavulanate?
3. 1.5 Intervention 1 and 2: Are clinical characteristics associated with response to 14 days treatment with antibiotics in children with CWC?
4. 1.6 Intervention 1 and 2: Are clinical characteristics before treatment associated with the time to relapse of CWC?
5. 1.7 Intervention 1 and 2: Describe the time to and number of relapses and results from further diagnostic investigations 12 and 24 months after end of treatment
6. 1.8.1 Intervention 1 and 2: To detect differences in Quality of life between children with CWC and healthy controls before treatment with antibiotics
7. 1.8.2 Intervention 1 and 2: To compare Quality of life in children with CWC before and after antibiotic treatment
8. 1.9.1 Intervention 1 and 2: To compare time to response to treatment in those receiving 14 days treatment with amoxicillin-clavulanate and those receiving placebo.
9. 1.9.2 Intervention 1 and 2: To compare the trajectories of VCD scores in those receiving 14 days treatment with amoxicillin-clavulanate and those receiving placebo.
10. 2.1.1 Intervention 1 and 2: To detect respiratory pathogens (virus, bacteria) in children with CWC before treatment with antibiotics.
11. 2.2.1 Intervention 1 and 2: To detect differences in respiratory pathogens (virus, bacteria) between children with CWC and healthy controls before treatment with antibiotics.
12. 2.2.2 Intervention 1 and 2: To detect differences in the diversity/composition of airway and gut microbiome in children with CWC and healthy controls before treatment with antibiotics.
13. 2.3.1 Intervention 1 and 2: To compare proportions in respiratory pathogens (virus, bacteria) in children with CWC at three timepoints (before and after treatment with antibiotics and after 6 months follow-up) and if changes are different from those of healthy controls.
14. 2.3.2 Intervention 1 and 2: To detect differences in the diversity/composition of airway and gut microbiome in children with CWC at three time points (before and after treatment with antibiotics and after 6 months follow-up) and if changes are different from those of healthy controls.
15. 2.4.1 Intervention 2: To compare proportions of respiratory pathogens (virus, bacteria) between children having received 14 days vs. 28 days treatment with antibiotics.
16. 2.4.2 Intervention 1 and 2: To describe differences in the diversity/composition of airway and gut microbiome between children having received 14 days vs 28 days treatment with antibiotics.
17. 3.1 Intevention 1: To compare inflammatory markers and patterns of these markers in laryngeal aspirate and peripheral blood in children with CWC and healthy controls.
18. 3.2 Intervention 1: To compare inflammatory markers and patterns of these markers in laryngeal aspirate and peripheral blood in children with CWC before and after antibiotic treatment.
19. 3.3.1 Intevention 1: To compare functional markers of primary immunodeficiencies (PID) in children with CWC and healthy controls.
20. 3.3.2 Intervention 1 and 2: To compare the prevalence of PID in children with CWC with the prevalence known from the normal population by performing Next-generation sequencing (NGS) panel for PID

Conditions and MedDRA coding

Chronic wet cough in young children

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age > 9 and younger than 36 months.
2. Body weight > 7 kg - < 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 inclusion ≥ 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 eligble for treatment with Augmentin.

Exclusion criteria 18

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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Response to treatment of amoxicillin-clavulanate is defined as baseline cough score ≤2 in validated Verbal category descriptive (VCD) cough score at the end of treatment or cessation of coughing (VCD =0) for a minimum period of 3 days within the treatment period. VCD score (0-10 points) will be reported by parents. Baseline cough score is the mean cough score of the three days before start of treatment (days -3 to -1).
2. Time to relapse is defined as the time from end of treatment (FU1) to start of relapse. Relapse of symptoms is defined as a new period of wet cough - after a period of at least seven 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 with cough of such a period or episode.

Secondary endpoints 8

1. Respiratory pathogens (virus and bacteria) detected by conventional methods (PCR and culture) in children with CWC and healthy controls.
2. Airway and gut microbiome diversity/composition in children with CWC and healthy controls
3. Inflammatory markers and patterns of these markers in laryngeal aspirate and peripheral blood from children with CWC compared and healthy controls.
4. Functional markers (not genetics) of Primay immunodeficiencies (PID) (Immunoglobulins, lymphocyte populations, complement function, vaccine response) in children with CWC and healthy controls.
5. Proportion of children diagnosed with primary immunodeficiencies (PID) based on Next-generation sequencing (NGS) panel for PID in children with CWC.
6. Day by day response to treatment (≤2 in VCD score)in those receiving 14 days treatment with amoxicillin-clavulanate and those receiving placebo.
7. Quality of life score in children with CWC and controls.
8. Day by day response to treatment (≤2 in VCD score).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stavanger University Hospital

Sponsor organisation

Stavanger University Hospital

Address

Postboks 8100

City

Stavanger

Postcode

4068

Country

Norway

Scientific contact point

Organisation

Stavanger University Hospital

Contact name

Knut Øymar

Public contact point

Organisation

Stavanger University Hospital

Contact name

Knut Øymar

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

4 submissions — initial application plus substantial / non-substantial modifications