The Norwegian Antibiotics for Pneumonia in Children Study (NAPiC)

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.

Study Overview

• Status: Unknown
• Conditions: Lower Respiratory Tract Infection; Pneumonia Childhood
• Intervention / Treatment: Drug: Amoxicillin; Drug: Placebos

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 Type: Interventional
• Enrollment (Anticipated): 884
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Bergen, Norway, 5021
    • Not yet recruiting
    • Haukeland University Hospital
    • Contact: Håvard Trønnes, PhD; Phone Number: 95777862; Email: havard.tronnes@ihelse.net
    • Principal Investigator: Håvard Trønnes, PhD
  • Bodø, Norway, 8005
    • Recruiting
    • Nordlandssykehuset Bodø
    • Contact: Bjørg Evjenth; Phone Number: 99258992; Email: bjorg.evjenth@gmail.com
    • Principal Investigator: Bjørg Evjenth, PhD
  • Grålum, Norway, 1714
    • Not yet recruiting
    • Østfold Hospital Trust
    • Contact: Jon Olav Hunderi, MD; Phone Number: 91880816; Email: jon.olav.gjengsto.hunderi@so-hf.no
    • Principal Investigator: Jon Olav Hunderi, M.D.
  • Lørenskog, Norway, 1478
    • Not yet recruiting
    • Akershus University Hospital
    • Contact: Christopher Inchley; Phone Number: 90069276; Email: christopher.inchley@medisin.uio.no
    • Principal Investigator: Christopher Inchley, PhD
  • Oslo, Norway, 0424
    • Recruiting
    • Oslo University of Oslo
    • Contact: Håvard O Skjerven, PhD; Phone Number: 41020249; Email: h.o.skjerven@medisin.uio.no
    • Contact: Email: h.o.skjerven@medisin.uio.no
    • Sub-Investigator: Håvard O Skjerven, PhD
    • Principal Investigator: Per Kristian Knudsen, MD
  • Stavanger, Norway, 4011
    • Recruiting
    • Stavanger University Hospital
    • Contact: Knut Øymar, PhD; Phone Number: 41633426; Email: knut.oymar@sus.no
    • Principal Investigator: Knut Øymar, PhD
  • Tromsø, Norway, 9038
    • Not yet recruiting
    • University Hospital of Northern Norway
    • Contact: Claus Klingenberg; Phone Number: 91563167; Email: claus.klingenberg@unn.no
    • Principal Investigator: Claus Klingenberg
  • Trondheim, Norway, 7030
    • Not yet recruiting
    • St. Olav University Hospital
    • Contact: Henrik Döllner, PhD; Phone Number: 47667169; Email: henrik.dollner@ntnu.no
    • Principal Investigator: Henrik Döllner, PhD
  • Ålesund, Norway, 6017
    • Recruiting
    • Ålesund Hospital Trust
    • Contact: Torbjørn Nag; Phone Number: 41638349; Email: torbjorn.nag@helse-mr.no
    • Principal Investigator: Torbjørn Nag, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amoxicillin; Amoxicillin 100mg/ml mixture (Imacillin), 0.25ml/kg every 8 hours for 7 days.	Drug: Amoxicillin; Imacillin mixture; Other Names: Imacillin
Placebo Comparator: Placebo; Placebo mixture 0.25ml/kg every 8 hours for 7 days	Drug: Placebos; Placebo manufactured to mimic amoxicillin mixture (Imacillin)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: Norwegian Institute of Public Health; University Hospital of North Norway; Ostfold Hospital Trust; Helse Stavanger HF; Haukeland University Hospital; St. Olavs Hospital; Alesund Hospital; University Hospital, Akershus; Nordlandssykehuset HF; Klinbeforsk
• Investigators: Principal Investigator: Håvard O Skjerven, Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2018
• Primary Completion (Anticipated): May 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: February 17, 2018
• First Submitted That Met QC Criteria: February 23, 2018
• First Posted (Actual): February 26, 2018

Study Record Updates

• Last Update Posted (Actual): April 11, 2018
• Last Update Submitted That Met QC Criteria: April 10, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: pneumonia; antibiotics; amoxicillin; pre-school children
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Respiratory Tract Infections; Anti-Infective Agents; Anti-Bacterial Agents; Amoxicillin
• Other Study ID Numbers: 2017/1863

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No