Twice Daily Treatment With Amoxicillin for Non-severe Community Acquired Pneumonia.

Treatment of Non-severe Community Acquired Pneumonia With Twice Daily Compared to Thrice Daily Regimen- A Non-inferiority Pragmatic Randomized-controlled Trial.

The aim of this study will be to evaluate whether a twice-daily antibiotic regimen is non-inferior to a thrice-daily regimen for the treatment of non-severe community acquired pneumonia in children presenting at a paediatric Emergency Department (ED).

Study Overview

• Status: Recruiting
• Conditions: Community-acquired Pneumonia
• Intervention / Treatment: Drug: Amoxicillin

Detailed Description

A single-center, non-blinded, pragmatic, randomized-controlled, non-inferiority clinical trial will be conducted in an urban, university-affiliated, tertiary care pediatric hospital ED. All patients three months old to 18 years of age who had symptoms and signs suggestive of non-severe community acquired pneumonia based on respiratory complaints and a pulmonary infiltrate identified by trained paediatricians or emergency physicians will be eligible to the present study. Study participants will be randomly allocated to receive either amoxicillin (90mg/kg per day) in twice or thrice daily regimen. Primary outcome will be treatment failure within 10 days of enrolment as defined by hospitalisation, need for a change in antibiotic (persistence of fever at 72 hours, clinical deterioration, comorbid condition or development of serious adverse reactions) and death. ED revisits within 72 hours, second course of antibiotic and clinical recurrence rates will be evaluated in the follow-up assessments as well as percent of adverse events encountered, number of days missed (work, school or daycare), coverage vaccination rate, protocol adherence and patient and parental satisfaction. The primary analysis will use an intention-to-treat approach. Per-protocol analysis will also be carried to compare the failure rate. Accounting to a maximal 10% drop-off rate, a sample size of 685 participants per arm was calculated to have a power of 90% to identify a difference of ≤ 5% with an alpha value of 0.05.

• Study Type: Interventional
• Enrollment (Anticipated): 1370
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Ariane Boutin, MD; Phone Number: 514-345-4931; Email: arianeboutin@gmail.com

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T1C5
      • Recruiting
      • CHU Sainte-Justine
      • Contact: Ariane Boutin, MD; Phone Number: 514-345-4931; Email: arianeboutin@gmail.com
      • Principal Investigator: Boutin Ariane, MD
      • Sub-Investigator: Benoit Carriere, MD
      • Sub-Investigator: Marc Lebel, MD
      • Sub-Investigator: Michel Roy, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients 3 months to 18 years of age attending the pediatric ED and diagnosed with a non-severe pneumonia, will be considered for enrolment. More precisely, the following inclusion criteria will be required:

  1. Presence of respiratory symptoms (cough and/or dyspnea)
  2. Presence of signs of pneumonia (tachypnea, abnormal breath sounds, crackles)
  3. Presence of fever
  4. Positive chest radiography as interpreted by the treating physician

Exclusion Criteria:

• Any danger signs associated with pneumonia (severe indrawing, shock or severe dehydration, empyema, important pleural effusion, pulmonary abcess or pneumatocoele)
• History of anaphylactic or allergic reaction to penicillin or amoxicillin according to the treating physician.
• History of a serious nonimmunoglobulin E-mediated reactions (eg, Stevens-Johnson syndrome or toxic epidermal necrolysis) attributed to amoxicilin.
• Caregiver unable to provide consent (language barrier or lack of caregiver presence)
• Underlying unstable chronic illness (ie. cystic fibrosis, immune suppression, active tuberculosis, bronchiectasis or active pulmonary malignancies)
• Persistent/chronic pneumonia syndromes (with symptoms for >2 weeks), suspected by the physician to be caused by atypical pathogens, hospital- acquired pneumonia (been hospitalized within 2 weeks prior to enrolment), aspiration pneumonia or recurrent pneumonias.
• Any history of receiving amoxicillin within the past month
• Need hospitalisation for any other reasons (ie. persistent vomiting, severe life-threatening infection such as septicaemia or meningitis requiring intravenous antimicrobial agents)
• Previous participation in study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Twice a day regimen; Patients will received a prescription of amoxicillin (90mg/kg/day) divided in two doses daily.	Drug: Amoxicillin; (90 mg/kg/day) twice daily; Other Names: Amoxil
ACTIVE_COMPARATOR: Thrice a day regimen; Patients will received a prescription of amoxicillin (90mg/kg/day) divided in three doses daily.	Drug: Amoxicillin; (90 mg/kg/day) twice daily; Other Names: Amoxil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical failure within 10 days of enrolment	As a primary outcome, clinical failure will be defined by any of the following occurring within 10 days of enrolment: Death or hospitalisation; A need for a change in antibiotic according to the treating physician. In our settings, common reasons to change antibiotic are:Persistence of fever at 72hClinical deterioration:• Clinical deterioration will include the development of lower chest-wall indrawing, central cyanosis, stridor while calm, or danger signs as defined by: inability to drink or breastfeed, convulsions, persistent vomiting, lethargy, or unconsciousness at any time during a child's treatment.Development of a comorbid condition such as a meningitis, bacteriemia, osteomyelitis or septic arthritisAllergic reaction	Day 10 (after enrolment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Emergency department revisit within 72 hours	Return to the emergency department in the following 72 hours	72 hours
Second course of antibiotic	Necessity of second course of antibiotics	1 month
Clinical recurrence	Another diagnosis of pneumonia	1 month
Adverse events	Any adverse event	10 days
Number of working days missed by caregivers or school/daycare days missed by patients	Total number of days missed by caregivers or school/daycare days missed by the parents	1 month
Patient's and parents satisfaction with the discharge instructions' provided and the ease of administration	Measured on a likert scale through a telephone survey	10 days

Collaborators and Investigators

• Sponsor: St. Justine's Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 11, 2017
• Primary Completion (ANTICIPATED): June 1, 2024
• Study Completion (ANTICIPATED): June 1, 2024

Study Registration Dates

• First Submitted: January 23, 2017
• First Submitted That Met QC Criteria: January 24, 2017
• First Posted (ESTIMATE): January 25, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 5, 2022
• Last Update Submitted That Met QC Criteria: May 3, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Non-severe community-acquired pneumonia; Amoxicillin treatment; Twice daily antibiotic regimen
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Anti-Infective Agents; Anti-Bacterial Agents; Amoxicillin
• Other Study ID Numbers: BID pneumonia

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
• product manufactured in and exported from the U.S.: No