Short-course Antimicrobial Therapy for Paediatric Respiratory Infections

NCT02380352 | Completed Phase 4 DMC

• 1 other identifier: SAFER 001 PSI
• Study Type: interventional
• Target: 281
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Community-acquired Pneumonia

Keywords

antibiotic stewardship; non-inferiority; randomized controlled trial

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

Study Arms (2)

Short-course

EXPERIMENTAL

5 days amoxicillin 90 mg/kg/day divided TID followed by 5 days placebo TID

Drug: Amoxicillin; Drug: Placebo

Standard

ACTIVE COMPARATOR

5 days amoxicillin 90 mg/kg/day divided TID followed by alternate formulation 5 days amoxicillin 90 mg/kg/day divided TID

Drug: Amoxicillin

Interventions

Amoxicillin DRUG

Also known as: Amoxil

Short-course; Standard

Placebo DRUG

Experimental arm must receive 5 days placebo after 5 days amoxicillin to preserve blinding.

Short-course

Eligibility Criteria

• Age: 6 Months - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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:
• 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;
• any one of:
• 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);
• cough on exam or by history;
• increased work of breathing on exam; or
• auscultatory findings (focal crackles, bronchial breathing, etc.) consistent with pneumonia;
• infiltrates on chest radiograph consistent with bacterial CAP as judged by the ED physician; and
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hamilton Health Sciences Corporation: lead
• Children's Hospital of Eastern Ontario: collaborator

Study Sites (2)

McMaster Children's Hospital

Hamilton, Ontario, L8S 4K1, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Location

Related Publications (2)

• 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.

  PMID: 33683325 DERIVED

• 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.

  PMID: 29391051 DERIVED

MeSH Terms

Conditions

Community-Acquired Pneumonia

Interventions

Amoxicillin

Condition Hierarchy (Ancestors)

Community-Acquired Infections; Infections; Pneumonia; Respiratory Tract Infections; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jeffrey M Pernica, MD

  McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2015
• First Posted: March 5, 2015
• Study Start: September 1, 2016
• Primary Completion: December 1, 2019
• Study Completion: April 1, 2020
• Last Updated: June 8, 2021

Record last verified: 2021-05

Locations

CA (2)