Protracted Bacterial Bronchitis
Conditions
Keywords
Chronic wet cough, Antibiotic, Children, Microbiology, Immunology
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.
Interventions
DRUGAmoxicillin-Clavulanate 400 Mg-57 Mg/5 mL Oral Powder for Reconstitution
Three times daily
DRUGPlacebo
Three times daily
Sponsors
Oslo University Hospital
Haukeland University Hospital
Alesund Hospital
University Hospital, Akershus
Trondheim University Hospital
University Hospital of North Norway
Helse Stavanger HF
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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.
Eligibility
Sex/Gender
ALL
Age
9 Months to 36 Months
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response to treatment | Response to treatment will be assessed 14 days after end of antibiotic 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.The VCD score has a minimum and maxiumum score ranging from 0-10 points, and a higher value corresponds to more severe cough. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relapse of symptoms | Relapse of symptoms will be assessed up to 24 months after end of antibiotic treatment | 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. |
Countries
Norway
Contacts
Primary ContactKnut Øymar, MD PhD
Backup ContactIngvild B Mikalsen, MD PhD
Outcome results
None listed