Clinical trial NCT03031210: Twice Daily Treatment With Amoxicillin for Non-severe Community Acquired Pneumonia.
Official title: Treatment of Non-severe Community Acquired Pneumonia With Twice Daily Compared to Thrice Daily Regimen- A Non-inferiority Pragmatic Randomized-controlled Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Community-acquired Pneumonia
Keywords: Non-severe community-acquired pneumonia
Amoxicillin treatment
Twice daily antibiotic regimen
Lead sponsor: St. Justine's Hospital
Sponsor class: OTHER
First posted: 2017-01-25
Enrollment: 1370
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical failure within 10 days of enrolment
timeFrame: Day 10 (after enrolment)
Secondary outcomes:
measure: Emergency department revisit within 72 hours
timeFrame: 72 hours
measure: Second course of antibiotic
timeFrame: 1 month
measure: Clinical recurrence
timeFrame: 1 month
measure: Adverse events
timeFrame: 10 days
measure: Number of working days missed by caregivers or school/daycare days missed by patients
timeFrame: 1 month
measure: Patient's and parents satisfaction with the discharge instructions' provided and the ease of administration
timeFrame: 10 days
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
Study officials:
affiliation: Sainte-Justine Hospital
name: Jocelyn Gravel, MD
role: PRINCIPAL_INVESTIGATOR
References: