Advanced Diagnostics for Enhanced QUality of Antibiotic Prescription in Respiratory Tract Infections in Emergency Rooms

Not Applicable

Completed

• Conditions: Community-acquired Acute Lower Respiratory Infection
• Interventions: Device: BioFire FilmArray Respiratory Panel 2.1 plus (RP2.1plus)

• Registration Number: NCT04781530
• Lead Sponsor: PENTA Foundation

Brief Summary

This study is a randomized controlled trial where participants are randomly assigned in a 1:1 ratio to either a rapid test group or a control group. Standard care is provided in the control group. Follow-up is conducted until discharge from the hospital, followed by telephone check-ins and completion of questionnaires by the participants themselves or their proxies until 30 days after randomization. Children of any age presenting at selected participating sites with acute respiratory tract infections, where initial treatment decisions are uncertain, are eligible to participate. The study aims to enrol 520 participants and involves Paediatric Emergency Rooms across Europe.

Detailed Description

Background. Community-acquired acute respiratory tract infections (CA-ARTI) are among the most frequent infectious diseases worldwide. Uncomplicated ARTI is the most frequent cause of inappropriate antibiotic use, and there is a need of more judicious antibiotic prescribing to prevent exposure to drug-related adverse events and selection of antibiotic resistance. There is a need to assess the impact of rapid syndromic diagnostic testing in patients with CA-ARTI presenting to Emergency Rooms on clinical decision making related to hospitalisation and prescription of antibiotics. At the same time it must be determined whether the decisions guided by the rapid syndromic diagnostic testing results do not compromise patient safety.

Trial objective: To assess the impact of rapid diagnostic testing in patients with ARTI at the emergency department, on (1) hospital admission rates, (2) antimicrobial prescriptions (days of treatment) and (3) non-inferiority in terms of clinical outcome.

Secondary objectives include health care utilisation, time away from school or routine childcare arrangements and quality of life.

In an ancillary study, changing patterns in microbiological colonisation of the oropharynx following different management strategies will be assessed in a subset of participants.

Study design: Individually randomised controlled trial, randomisation 1:1 to either a rapid test group (intervention described below) or a control group, with management according to standard of care at the local facility. Follow-up until discharge from hospital and thereafter by telephone follow-up and self (or proxy)-completion questionnaires until 30 days after randomisation.

Study population: Children of any age consulting in selected participating sites with CA-ARTI, in which there is initial uncertainty about treatment and management decisions, after provision of informed consent by parent(s) or legal guardian.

Study Intervention: The diagnostic intervention is rapid syndromic testing on a nasopharyngeal swab with BioFire FilmArray Respiratory Panel 2.1 plus (RP2.1plus) (licensed for routine use at all trial sites), results expected within four hours from sample collection.

Co-primary endpoints:

Hierarchical nested analysis design of:

* Days alive out of hospital (superiority endpoint), within 14 days after study enrolment

* Days on Therapy (DOT) with antibiotics (superiority endpoint), within 14 days after study enrolment

Secondary endpoints Adverse outcome (non-inferiority safety endpoint)

•Safety endpoint: For initially hospitalised patients: i) any readmission, ii) ICU admission =\> 24 hours after hospitalisation, or iii) death, within 30 days after study enrolment

For initially non-admitted patients: any admission or death within 30 days after study enrolment.

* Direct costs and indirect costs within 30 days after enrolment.

* Change in quality of life as determined by EQ-5D-5L (or suitable alternative for age), days away from usual childcare routine or school and healthcare utilisation on day 1, 14, and 30 after enrolment.

* Microbiological results obtained as standard of care and with the diagnostic intervention

* Empirical antibiotics, antibiotic type switches, de-escalation based on antimicrobial agent categories. Prescription of antivirals during the main study.

* Detection of antimicrobial resistance (carriage or infection) related to the diagnostic intervention results compared to standard of care and impact on antimicrobial stewardship guidelines and prevention of hospital acquired infections.

* Impact on decisions regarding isolation measures related to test result.

Study Timeline

• Study First Submitted: 2021-02-02
• Study First Submitted QC: 2021-03-01
• Study First Posted: 2021-03-04
• Study Start: 2021-07-07
• Primary Completion: 2024-01-25
• Study Completion: 2024-01-25
• Status Verified: 2024-12
• Last Update Submitted: 2025-04-15
• Last Update Posted: 2025-04-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 522

Inclusion Criteria

1. Children of any age presenting to the Emergency Room with an acute illness (present for 14 days or less) with Temperature ≥38.0°C measured at presentation or reported within the previous 24 hours

   AND at least two of the below:

   • Cough
   • Abnormal sounds on chest auscultation (crackles, reduced breath sounds, bronchial breathing, wheezing)
   • Clinical signs of dyspnea (chest indrawing, nasal flaring, grunting)
   • Signs of respiratory dysfunction: tachypnoea for age or decreased oxygen saturation (<92% in room air)
   • Signs of reduced general state: poor feeding, vomiting or lethargy/drowsiness

2. At time of screening:

   • Patient has undergone first assessment by managing clinical team (doctor or nurse, incl. triage)
   • Hospitalisation is not yet determined, i.e. neither by clinical presentation definitely requiring hospitalisation (e.g. per local guideline) nor by fixed decision of managing clinical team; admission to a short-stay unit or surveillance unit is not considered a hospitalisation for this trial
   • Antibiotic treatment or hospitalisation is being considered
   • The rapid syndromic diagnostic test result can be awaited for up to 4 hours before the decision to discharge the patient or to initiate antibiotic treatment is made

Exclusion Criteria

1. Development of ARTI more than 48 hours after hospital admission (hospital acquired);
2. Patients with a severe underlying medical condition dictating management decisions including hospitalisation and/or antibiotic treatment (e.g cystic fibrosis, immunosuppression);
3. Less than 14 days since the last episode of respiratory tract infection;
4. Confirmed pregnancy and/or breastfeeding;
5. Any clinically significant abnormality identified at the time of screening that in the judgment of the Investigator would preclude safe completion of the study or constrain endpoints assessment such as major systemic diseases or patients with short life expectancy;
6. Inability to obtain informed consent;
7. Alternative noninfectious diagnosis that explains clinical symptoms.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention (Device)	BioFire FilmArray Respiratory Panel 2.1 plus (RP2.1plus)	Diagnostic Test: BioFire A molecular rapid syndromic testing platform, using the following panel: BioFire FilmArray Respiratory Panel 2.1 plus (RP2.1plus) In addition to standard of care

Primary Outcome Measures

Name	Time	Method
Days alive out of hospital (superiority endpoint), within 14 days after study enrolment	14 days	Days alive out of hospital (superiority endpoint), within 14 days after study enrolment
Days on Therapy (DOT) with antibiotics (superiority endpoint), within 14 days after study enrolment	14 days	Days on Therapy (DOT) with antibiotics (superiority endpoint), within 14 days after study enrolment
Adverse outcome (non-inferiority safety endpoint)	30 days	Adverse outcome (non-inferiority safety endpoint); * For initially non-admitted patients: any admission or death within 30 days; * For initially hospitalised patients: i) any readmission, ii) ICU admission \>= 24 hours after hospitalisation, or iii) death, all within 30 days

Secondary Outcome Measures

Name	Time	Method
Antibiotic type switches and de-escalation based on antimicrobial agent categories	Day 1 - Day 14	Time to de-escalation and time to stop of anti-infective therapy
Direct costs and indirect costs within 30 days after enrolment.	30 days	* Cost of healthcare within 30 days after enrolment, including hospital and ICU days, utilisation of non-hospital services and cost of anti-infective and concomitant medication; * Cost of workdays lost within 30 days, including days for childcare
Quality of life as determined by EQ5D-5L (or suitable alternative for age), days away from usual childcare routine or school and healthcare utilisation on day 1, 14, and 30 after enrolment.	1, 14 and 30 days	Quality of life as determined by EQ5D-5L (or suitable alternative for age), days away from usual childcare routine or school and healthcare utilisation on day 1, 14, and 30 after enrolment.
Microbiological results obtained as standard of care and with the diagnostic intervention	Day 1	Proportion of participants with an identified respiratory pathogen in both study groups on randomisation day samples.
Empirical antibiotics based on antimicrobial agent categories	Day 1 - Day 14	Proportion of participants on non-first-line anti-infective regimens (as defined by local guidelines)
Impact on decisions regarding isolation measures related to test result.	Day 1 - Day 30	Hours in individual or cohort isolation in hospitalised participants
Detection of antimicrobial resistance (carriage or infection) related to the diagnostic intervention results compared to standard of care and impact on antimicrobial stewardship guidelines and prevention of hospital acquired infections	>7 days after randomisation	Proportion of hospitalised participants with detection of cephalosporin-, carbapenem- or chinolone-resistant Enterobacteriaceae on any standard of care samples \>7 days after randomisation

Trial Locations

Locations (6)

University Children's Hospital Tuebingen; 🇩🇪 Tuebingen, Germany

Hippokration Hospital of Thessaloniki; 🇬🇷 Thessaloniki, Greece

Hospital Universitario 12 de Octubre, Spain; 🇪🇸 Madrid, Spain

Ospedale Regionale Bellinzona e Valli; 🇨🇭 Bellinzona, Switzerland

University Hospital of Lewisham; 🇬🇧 London, United Kingdom

University Children's Hospital Basel (UKBB); 🇨🇭 Basel, Basel-Stadt, Switzerland