Clinical trial NCT03446534: The Norwegian Antibiotics for Pneumonia in Children Study
Official title: The Norwegian Antibiotics for Pneumonia in Children Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Pneumonia Childhood
Lower Respiratory Tract Infection
Keywords: pneumonia
pre-school children
antibiotics
amoxicillin
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: Ostfold Hospital Trust
name: Helse Stavanger HF
name: Haukeland University Hospital
name: Alesund Hospital
name: St. Olavs Hospital
name: Nordlandssykehuset HF
name: University Hospital of North Norway
name: University Hospital, Akershus
name: Norwegian Institute of Public Health
name: Klinbeforsk
First posted: 2018-02-26
Enrollment: 884
Sex: ALL
Minimum age (years): 12
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study is a phase IV double-blind, placebo-controlled, multicenter, nationwide, randomized superiority trial of amoxicillin versus placebo in children aged 1-5 years of age with a lower respiratory infection.
Primary purpose: TREATMENT

Brief summary: This study evaluates the effect of amoxicillin in the treatment of lower airway infections in preschool children. Half of the patients will receive amoxicillin, while the other half will receive placebo.

Detailed description: The overall objective of the study is to determine if antibiotic therapy is beneficial in children with pneumonia who do not have a highly suspicious bacterial infection, such as in lobar pneumonia.

Secondary objective is to determine whether antibiotic use influence the microbial flora, including antibiotic resistance, in the airways in the short or medium long term.

The study is a phase IV double-blind, placebo-controlled, multicenter, nationwide, randomized superiority trial of amoxicillin versus placebo in children aged 1-5 years of age with a lower respiratory infection.

Eligibility criteria: Inclusion Criteria:

1. Age 12-59 months
2. Fever:

   a. Temperature ≥ 38.0 at inclusion or reported within the last 24 hours
3. Tachypnoe, age specific 12-17mnd ≥ 46 breaths per minute 18-23mnd ≥ 40 breaths per minute 24-35mnd ≥ 34 breaths per minute 36-47mnd ≥ 29 breaths per minute 48-59mnd ≥ 27 breaths per minute
4. ≥ 1 sign of lower airway inflammation

   1. Cough (at inclusion or reported within the last 6 hours)
   2. Chest retractions (jugular, intercoastally or subcoastally)
   3. Grunting respiration
   4. Nasal flaring
   5. Crepitations by pulmonary auscultation
   6. Hypoxia (SpO2 ≤ 90%)
5. Weight between 6.0 and 28.0 kg. • Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations

Exclusion Criteria:

1. Clinical suspicion of bacterial pneumonia based upon a temperature ≥39.0°C and at least one of the following:

   1. Bronchial breathing sounds
   2. Unilaterally decreased breath sounds or unilateral percussion dullness
   3. Pulmonary lobar consolidation and/or radiological high suspicion of empyema on chest x-ray if this is obtained prior to inclusion in the trial.
2. Evidence of any bacterial infection requiring systemic antibiotics, including, but not exclusively:

   1. Clinical septicaemia
   2. Urinary tract infection
   3. Meningitis
3. Systemic antibiotics received within the last 7 days
4. Pulmonary lobar consolidation and/or radiological high suspicion of empyema on chest x-ray if this is obtained prior to inclusion in the trial.
5. History of any serious underlying disease that can increase the risk of bacterial pulmonary infections, including but not limited to:

   1. Haematological or oncological
   2. Immunodeficiency
   3. Congenital heart disease
   4. Neuromuscular impairment
   5. Development disorder, including Downs syndrome
   6. Bronchopulmonary dysplasia, cystic fibrosis, primary ciliary dyskinesia, poorly controlled asthma or other severe chronic lung diseases
6. Signs of lower obstructive airways with both of the following present by auscultation:

   1. prolonged expiration and
   2. generalised expiratory wheeze
7. Stridor by auscultation.
8. History of known or suspected adverse reactions to amoxicillin, or any other betalactam
9. Participating in another trial that might affect the current study
10. Any reason why, in the opinion of the investigator, the patient should not participate (e.g. not able to comply with study procedures)

Primary outcomes:
measure: Therapy Failure
timeFrame: Within 7 days after inclusion
Secondary outcomes:
measure: Thereapy failure leading to intravenous antibiotic therapy
timeFrame: Within 7 days after inclusion
measure: Duration of fever
timeFrame: Up to 21 days after inclusion
measure: Duration of symptoms of pneumonia
timeFrame: Up to 21 days after inclusion
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Bodø
country: Norway
facility: Nordlandssykehuset Bodø
city: Grålum
country: Norway
facility: Østfold Hospital Trust
city: Lørenskog
country: Norway
facility: Akershus University Hospital
city: Oslo
country: Norway
facility: Oslo University of Oslo
city: Stavanger
country: Norway
facility: Stavanger University Hospital
city: Tromsø
country: Norway
facility: University Hospital of Northern Norway
city: Trondheim
country: Norway
facility: St. Olav University Hospital
city: Ålesund
country: Norway
facility: Ålesund Hospital Trust
Study officials:
affiliation: Oslo University Hospital
name: Håvard O Skjerven
role: PRINCIPAL_INVESTIGATOR
References: