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

NCT06020716 | Recruiting Phase 4 FDA Drug

• 2 other identifiers: AMIC 20232022-500586-27-00
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 7

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.

Conditions

Protracted Bacterial Bronchitis

Keywords

Chronic wet cough; Antibiotic; Children; Microbiology; Immunology

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Relapse of symptoms

  Relapse of symptoms will be assessed up to 24 months after end of antibiotic treatment

Study Arms (4)

AMIC 1: Arm A

EXPERIMENTAL

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.

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

AMIC 1: Arm B

PLACEBO COMPARATOR

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.

Drug: Placebo

AMIC 2: Arm C

EXPERIMENTAL

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.

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

AMIC 2: Arm D

EXPERIMENTAL

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.

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

Interventions

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

Three times daily

AMIC 1: Arm A; AMIC 2: Arm C; AMIC 2: Arm D

Placebo DRUG

Three times daily

AMIC 1: Arm B; AMIC 2: Arm C

Eligibility Criteria

• Age: 9 Months - 36 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Age ≥ 9 and \< 36 months.
• Body weight ≥ 7 kg and \< 24 kg.
• Born term with Gestational age ≥ 37 weeks.
• 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.
• The study subject must be assessed as eligible for treatment with Augmentin.

You may not qualify if:

• Gestational age \< 37 weeks.
• History of acute upper or lower airway infection the last 2 weeks.
• History of other viral or bacterial infections the last 2 weeks.
• Episode with temperature above 38 °C during the last 2 weeks.
• Previous diagnosed with chronic lung disease such as cystic fibrosis, primary ciliary dyskinesia, interstitial lung disease, asthma, immunodeficiency, esophagus atresia.
• Cardiac disease, except persisting foramen ovale or ductus arteriosus.
• Severe feeding problems/aspiration.
• Gastroesophageal reflux suspicion or confirmed by ph measurement.
• Suspicion of hypertrophic tonsils or adenoids
• Episodes of bronchopulmonary obstruction suggesting asthma
• Presence of gross neurodevelopmental delay, or suspicion of neurological disease.
• History of known or suspected allergic reactions to amoxicillin-clavulanate or any other betalactam.
• Episodes with haemoptysis and with unknown cause.
• Radiographic changes other than perihilar changes confirmed by x-ray at screening.
• At examination: Digital clubbing, hypoxia, chest wall deformity, dyspnoea at rest.

Sponsors & Collaborators

• Helse Stavanger HF: lead
• Oslo University Hospital: collaborator
• Haukeland University Hospital: collaborator
• Alesund Hospital: collaborator
• University Hospital, Akershus: collaborator
• Trondheim University Hospital: collaborator
• University Hospital of North Norway: collaborator

Study Sites (7)

Ålesund Hospital

Ålesund, Norway

RECRUITING

Haukeland University Hospital

Bergen, Norway

RECRUITING

Akershus University Hospital

Lillestrøm, Norway

RECRUITING

Oslo University Hospital

Oslo, Norway

RECRUITING

Stavanger University Hospital

Stavanger, 40, Norway

RECRUITING

University Hospital of North-Norway

Tromsø, Norway

RECRUITING

Trondheim University Hospital

Trondheim, Norway

RECRUITING

MeSH Terms

Interventions

Amoxicillin-Potassium Clavulanate Combination

Intervention Hierarchy (Ancestors)

Clavulanic Acid; Clavulanic Acids; beta-Lactams; Lactams; Amides; Organic Chemicals; Amoxicillin; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Knut Øymar, MD PhD

  Helse Stavanger HF

  STUDY CHAIR

Central Study Contacts

Knut Øymar, MD PhD

CONTACT

+47 41633426; knut.oymar@sus.no

Ingvild B Mikalsen, MD PhD

CONTACT

+47 46892206; ingvild.bruun.mikalsen@sus.no

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 3, 2023
• First Posted: September 1, 2023
• Study Start: August 16, 2023
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2028
• Last Updated: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

NO (7)