Short-course Antimicrobial Therapy for Paediatric Respiratory Infections (SAFER)

Randomized controlled double-blind non-inferiority clinical trial to determine whether five days of high-dose amoxicillin leads to comparable rates of early clinical cure compared with 10 days of high-dose amoxicillin for previously healthy children with mild community-acquired pneumonia.

Study Overview

• Status: Completed
• Conditions: Community-acquired Pneumonia
• Intervention / Treatment: Drug: Amoxicillin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 281
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4K1
      • McMaster Children's Hospital
    • Ottawa, Ontario, Canada
      • Children's Hospital of Eastern Ontario

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 10 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Children aged 6 months to 10 years presenting with CAP will be eligible. CAP will be defined if all of the four following numeric criteria are met:

1. fever (>37.5 C axillary, > 37.7 C oral, or >38 C rectal) recorded in the ED or at home in the 48h prior to presentation;

2. any one of:

   1. tachypnoea on exam (>60 bpm for age <1 y, >50 bpm for 1-2 y of age, >40 bpm for 2-4 y of age, and >30 bpm for >4 y of age);
   2. cough on exam or by history;
   3. increased work of breathing on exam; or
   4. auscultatory findings (focal crackles, bronchial breathing, etc.) consistent with pneumonia;
3. infiltrates on chest radiograph consistent with bacterial CAP as judged by the ED physician; and
4. the attending ED physician diagnoses the child with primary CAP. (Children treated with systemic steroids in the ED will be presumed to have primary asthma exacerbation with possible infection and therefore will not meet inclusion criteria.)

Participants must be well enough to be treated as outpatients (discharged home by the ED physician, adequate volume status, able to tolerate oral medication, oxygen saturation > 90%, no evidence of impending respiratory failure), and have no evidence of empyaema or necrotizing pneumonia on chest radiograph.

Exclusion Criteria:

Children will be excluded if they have any of the following: cystic fibrosis, anatomic lung disease, bronchiectasis, congenital heart disease, history of repeated aspiration or velopharyngeal incompetence, malignancy, conditions requiring treatment with immune suppressants, primary immunodeficiency, advanced HIV infection, prolonged admissions (>48 h) to hospital within the past 2 months, pneumonia previously diagnosed within the past month, lung abscess diagnosed within the past six months, receipt of > 24 hours of beta-lactam antibiotic therapy already received at presentation to the ED, receipt of at least a 5 day course of amoxicillin < 72h prior to presenting to the ED, receipt of an intravenous cephalosporin or azithromycin in the ED, or suspected allergy to penicillin. Children will not be eligible to participate more than once.

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: Short-course; 5 days amoxicillin 90 mg/kg/day divided TID followed by 5 days placebo TID	Drug: Amoxicillin; Other Names: Amoxil; Drug: Placebo; Experimental arm must receive 5 days placebo after 5 days amoxicillin to preserve blinding.
Active Comparator: Standard; 5 days amoxicillin 90 mg/kg/day divided TID followed by alternate formulation 5 days amoxicillin 90 mg/kg/day divided TID	Drug: Amoxicillin; Other Names: Amoxil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early clinical cure (Resolution of tachypnoea, increased work of breathing, and fever)	Resolution of tachypnoea, increased work of breathing, and fever	at 14-21 days post-enrolment

Secondary Outcome Measures

Outcome Measure	Time Frame
Days of adverse reactions	up to 14 days post-enrolment
Days of missed school	up to 14 days post-enrolment
Days of missed/disrupted work for caregiver(s)	up to 14 days post-enrolment
Adherence to study medications	up to 10 days post-enrolment

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation
• Collaborators: Children's Hospital of Eastern Ontario
• Investigators: Principal Investigator: Jeffrey M Pernica, MD, McMaster University

Publications and helpful links

General Publications

• Pernica JM, Harman S, Kam AJ, Carciumaru R, Vanniyasingam T, Crawford T, Dalgleish D, Khan S, Slinger RS, Fulford M, Main C, Smieja M, Thabane L, Loeb M. Short-Course Antimicrobial Therapy for Pediatric Community-Acquired Pneumonia: The SAFER Randomized Clinical Trial. JAMA Pediatr. 2021 May 1;175(5):475-482. doi: 10.1001/jamapediatrics.2020.6735.
• Pernica J, Harman S, Kam A, Bailey J, Carciumaru R, Khan S, Fulford M, Thabane L, Slinger R, Main C, Smieja M, Loeb M. Short-course antimicrobial therapy for paediatric respiratory infections (SAFER): study protocol for a randomized controlled trial. Trials. 2018 Feb 1;19(1):83. doi: 10.1186/s13063-018-2457-2.

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): April 1, 2020

Study Registration Dates

• First Submitted: March 2, 2015
• First Submitted That Met QC Criteria: March 4, 2015
• First Posted (Estimate): March 5, 2015

Study Record Updates

• Last Update Posted (Actual): June 8, 2021
• Last Update Submitted That Met QC Criteria: May 27, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: randomized controlled trial; antibiotic stewardship; non-inferiority
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Respiratory Tract Infections; Anti-Infective Agents; Anti-Bacterial Agents; Amoxicillin
• Other Study ID Numbers: SAFER 001 PSI