Optimizing Care for Children Hospitalized With Community-acquired Pneumonia: Novel Diagnostics (PRESTO-1)

Optimizing Care for Children Hospitalized With Community-acquired Pneumonia: a Feasibility Randomized Controlled Trial of a Diagnostic Intervention

Children are commonly hospitalized because of community-acquired pneumonia. Despite the fact that many of these children have viral disease, a majority is treated with antibiotics. These antibiotics will not accelerate recovery in those with viral pneumonia and can cause harm. We are interested in exploring whether the MeMed BV - a composite biomarker assay - could be used to improve antibiotic prescribing in these children by identifying those who likely have viral disease. This proposal describes a feasibility randomized trial of this diagnostic intervention.

Study Overview

• Status: Recruiting
• Conditions: Community-acquired Pneumonia
• Intervention / Treatment: Diagnostic test: MeMed BV + Usual Care; Other: Usual Care Alone

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jeffrey Pernica, MD; Phone Number: 77577 9055212100; Email: pernica@mcmaster.ca
• Study Contact Backup: Name: Shamini Selvakumar, MD; Phone Number: 9055212100; Email: selvaks@mcmaster.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8S 4K1
      • Recruiting
      • McMaster Children's Hospital
      • Contact: Jeffrey Pernica, MD; Phone Number: 77577 9055212100; Email: pernica@mcmaster.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• children with a history of fever who are hospitalized with CAP (ie. 'severe CAP') as per the clinical team and who have abnormal chest imaging (eg. radiograph, ultrasound) will be eligible. They must also have at least one of the following:

  1. documented tachypnoea (>60 bpm for age <1 y, >50 bpm for 1-2 y, >40 bpm for 2-4 y, and >30 bpm for >4 y);
  2. cough on exam or by history;
  3. increased work of breathing on exam; or
  4. auscultatory findings (eg. focal crackles, bronchial breathing) consistent with CAP.

Exclusion Criteria:

• Children will be excluded from if they have received >48h of intravenous antibiotics (eg. if transferred from another healthcare facility) or if they have a lobar consolidation that occupies the majority of a lobe on imaging, a pleural effusion that occupies more than ¼ of a lung field, or a positive blood culture for a bacterial pathogen (not a contaminant). Examples of CAP pathogens include S. pneumoniae, S. pyogenes (group A streptococcus), S. aureus, S. anginosus. Examples of contaminants that would be ignored include the coagulase-negative staphylococci and Bacillus spp. Children will also be excluded if they have any of the following: chronic lung disease, congenital heart disease (requiring treatment or with exercise restrictions), malignancy, immunodeficiency (primary, acquired, or iatrogenic), a separate episode of pneumonia previously diagnosed within the past 2 weeks, or lung abscess diagnosed within the past six months. Children will not be eligible to participate more than once.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Usual Care	Other: Usual Care Alone; Usual care can involve oxygenation support, ventilatory support, intravenous fluids, and antibiotics, or any combination of these.
Experimental: MeMed BV	Diagnostic test: MeMed BV + Usual Care; We will aim to have blood drawn for MeMed BV testing within 24 hours of the first dose of IV antibiotics. We will then aim to have test results back within 24 hours of sampling.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consent success	The proportion of potentially eligible participants who consent	Day 0
MeMed BV test timing	The proportion of participants randomized to the diagnostic intervention who successfully have the MeMed BV performed within 24 h of receipt of the initial dose of IV antibiotics	before Day 2
MeMed BV test result reporting	The proportion of participants randomized to MeMed BV testing that have a test result available within 48h of sampling	before Day 3
MeMed BV test result initial adherence	The proportion of participants found to be high risk for viral infection that successfully have their antibiotics stopped within 24 hours of the test result becoming available	before Day 4
MeMed BV test result delayed adherence	The proportion of participants (who successfully had their antibiotics stopped) that do not have them restarted specifically for CAP treatment prior to discharge	before Day 15
Losses to followup	The proportion of participants lost to follow-up	before Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Early clinical response	This is defined as: i) clinical improvement in fever, work of breathing, oral intake, and activity level, AND ii) lack of receipt of additional antimicrobials beyond those already being given at baseline (for the control group) or as indicated by MeMed BV testing (for those randomized to the intervention group)	Day 4
Days of antibiotics given specifically for CAP before hospital discharge		Before discharge
Days of antibiotics given specifically for CAP after hospital discharge and before day 30		after hospital discharge and before day 30
Time to resolution of fever		Before discharge
Time to resolution of difficulty breathing		Before discharge
Time to resolution of hypoxaemia		Before discharge
Length of stay in hospital		Before discharge
Repeat hospitalization for CAP		After discharge and before day 30
Unscheduled ED or urgent care visits		After discharge and before day 30
Unscheduled primary care visits		After discharge and before day 30
Acceptability of care plan to caregiver		Baseline
Acceptability of care plan to caregiver		Day 30
Development of complicated pneumonia	Complicated defined by effusion, empyaema, necrotizing pneumonia	Before Day 30

Collaborators and Investigators

• Sponsor: Jeffrey

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2024
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: October 30, 2023
• First Submitted That Met QC Criteria: October 30, 2023
• First Posted (Actual): November 2, 2023

Study Record Updates

• Last Update Posted (Estimated): December 10, 2024
• Last Update Submitted That Met QC Criteria: December 8, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia
• Other Study ID Numbers: HHS-CB 2023-Pernica-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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