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

Protracted Bacterial Bronchitis Clinical Trial

— AMIC  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06020716
• Other study ID #: AMIC 2023
• Secondary ID: 2022-500586-27-0
• Status: Recruiting
• Phase: Phase 4
• Start date: August 16, 2023
• Est. completion date: April 30, 2028

Study information

• Verified date: April 2023
• Source: Helse Stavanger HF
• Contact: Knut Øymar, MD PhD
• Phone: +47 41633426
• Email: knut.oymar[@]sus.no
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 inflammatory markers in children with CWC and the impact of treatment with antibiotics. Furthermore, identify children with CWC who have primary immunodeficiency (PID) based on functional laboratory markers and genetic markers of PID.

The study will include two different interventions:

INTERVENTION 1:

Participants will be randomly assigned to 14 days antibiotics or placebo

INTERVENTION 2:

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

Description:

Study populations:

INTERVENTION 1:

90 children with chronic wet cough aged 9-36 months

INTERVENTION 2:

210 children with chronic wet cough aged 9-26 months

Both intervention groups 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, inflammatory markers and immunodeficiency, 50 healthy controls will be included for comparison to IV 1. The healthy controls will be followed for 6 months after inclusion.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: April 30, 2028
• Est. primary completion date: April 30, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 9 Months to 36 Months

Eligibility

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.

Related Conditions & MeSH terms

• Bronchitis
• Protracted Bacterial Bronchitis

Intervention

Drug:
• Amoxicillin-Clavulanate 400 Mg-57 Mg/5 mL Oral Powder for Reconstitution
Three times daily
• Placebo
Three times daily

Locations

Country	Name	City	State
Norway	Stavanger University Hospital	Stavanger

Sponsors (7)

Lead Sponsor	Collaborator
Helse Stavanger HF	Alesund Hospital, Haukeland University Hospital, Helse Nord, Oslo University Hospital, St. Olavs Hospital, University Hospital, Akershus

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response to 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.	Response to treatment will be assessed 14 days after end of antibiotic treatment
Secondary	Relapse of symptoms	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.	Relapse of symptoms will be assessed up to 24 months after end of antibiotic treatment