The Norwegian Antibiotics for Pneumonia in Children Study

Phase 4

• Conditions: Pneumonia Childhood; Lower Respiratory Tract Infection
• Interventions: Drug: Amoxicillin; Drug: Placebos

• Registration Number: NCT03446534
• Lead Sponsor: Oslo University Hospital

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.

Study Timeline

• Study First Submitted: 2018-02-17
• Study First Submitted QC: 2018-02-23
• Study First Posted: 2018-02-26
• Study Start: 2018-03-07
• Status Verified: 2018-04
• Last Update Submitted: 2018-04-10
• Last Update Posted: 2018-04-11
• Primary Completion: 2020-05
• Study Completion: 2020-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 884

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Amoxicillin	Amoxicillin	Amoxicillin 100mg/ml mixture (Imacillin), 0.25ml/kg every 8 hours for 7 days.
Placebo	Placebos	Placebo mixture 0.25ml/kg every 8 hours for 7 days

Primary Outcome Measures

Name	Time	Method
Therapy Failure	Within 7 days after inclusion	Therapy failure as defined by attending physician, leading to end of intervention and administration of open-label antibiotics

Secondary Outcome Measures

Name	Time	Method
Duration of fever	Up to 21 days after inclusion	Duration of fever
Thereapy failure leading to intravenous antibiotic therapy	Within 7 days after inclusion	Therapy failure as defined by attending physician, leading to intravenous antibiotic therapy
Duration of symptoms of pneumonia	Up to 21 days after inclusion	Duration of cough or respiratory distress (tachypnoe, retractions, grunting respiration or nasal flaring.

Trial Locations

Locations (9)

Ålesund Hospital Trust; 🇳🇴 Ålesund, Norway

Nordlandssykehuset Bodø; 🇳🇴 Bodø, Norway

Stavanger University Hospital; 🇳🇴 Stavanger, Norway

Haukeland University Hospital; 🇳🇴 Bergen, Norway

St. Olav University Hospital; 🇳🇴 Trondheim, Norway

Akershus University Hospital; 🇳🇴 Lørenskog, Norway

Oslo University of Oslo; 🇳🇴 Oslo, Norway

University Hospital of Northern Norway; 🇳🇴 Tromsø, Norway

Østfold Hospital Trust; 🇳🇴 Grålum, Norway