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

Study Overview
=================
Brief Summary
-----------------
To assess the impact of rapid diagnostic testing of patients with Acute Respiratory Tract Infection (ARTI) at the emergency department, on (1) hospital admission rates and (2) antimicrobial prescriptions (days of treatment) and (3) the non-inferiority in terms of clinical outcome. Geographical and seasonal variation will be assessed on a real time basis including pathogens of public health interest. The impact will be stratified within age groups and risk factors in order to determine the long-term clinical, public health and economic determinants for the integration of diagnostics in a global and sustainable perspective.

Official Title
-----------------
ADEQUATE Advanced Diagnostics for Enhanced QUality of Antibiotic Prescription in Respiratory Tract Infections in Emergency Rooms

Conditions
-----------------
Respiratory Tract Infections

Intervention / Treatment
-----------------
* Diagnostic Test: BioFire


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults (≥18 years old) presenting to the Emergency Room with an acute illness (present for 14 days or less) with cough, and with at least 1 other lower respiratory tract symptom or clinical sign at physical examination: Sputum production, Breathlessness, Chest discomfort or chest pain, Wheeze, Crackles, Self-reported dystermia or documented fever; Documented hypoxemia (adjusting definition for chronic oxygen therapy users, method of measurement) and no alternative explanation (infection, such as sinusitis; other, such as asthma). 2. Managing medical team considers: to treat patient with antibiotics and/or to hospitalize patient AND that the rapid syndromic diagnostic test result can be awaited up to a maximum of 4 hours before the decision to discharge the patient or to initiate antibiotic therapy. Exclusion Criteria: Development of ARTI more than 48 hours after hospital admission (hospital acquired); Patients with cystic fibrosis; Less than 14 days since the last episode of respiratory tract infection; Pregnancy (confirmed by pregnancy test) and breastfeeding; 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; Inability to obtain informed consent from a competent patient. Based on standard of care microbiological diagnosis and thoracic imaging (when indicated): Radiologically confirmed acute lobar pneumonia; Known or suspected Pneumocystis jirovecii pneumonia or active tuberculosis; Alternative noninfectious diagnosis that explains clinical symptoms (pulmonary embolism, alveolar hemorrhage, acute heart failure, lung cancer).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br> | Diagnostic Test: BioFire<br>* A molecular rapid syndromic testing platform, using the following panels: BioFire FilmArray Respiratory Panel 2.1 plus (RP2.1plus) BioFire FilmArray Pneumonia Panel plus (PP)<br>|
| No Intervention: Standard of Care<br> | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days alive out of hospital (superiority endpoint) |  | Day 1 - Day 14 | 
| Days on Therapy (DOT) with antibiotics (superiority endpoint) |  | Day 1 - Day 14 | 
| Adverse outcome (non-inferiority safety endpoint) | For initially non-admitted patients: any admission or death For initially hospitalized patients: any readmission, ICU admission >= 24 hours after hospitalization, or death | Day 1 - Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Direct costs and indirect costs within 30 days after enrolment. | 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 | Day 1 - Day 30 | 
| Quality of life as determined by EQ5D-5L (or suitable alternative for age), days away from work if applicable, and healthcare utilisation on day 1, 14, and 30 after enrolment. | Quality of life as determined by EQ5D-5L (or suitable alternative for age), days away from work if applicable, and healthcare utilisation on day 1, 14, and 30 after enrolment. | Day 1, 14, 30 | 
| Microbiological results obtained as standard of care and with the diagnostic intervention | Proportion of participants with an identified respiratory pathogen in both study groups on randomisation day samples. | Day 1 | 
| Empirical antibiotics based on antimicrobial agent categories | Proportion of participants on non-first-line anti-infective regimens (as defined by local guidelines) | Day 1 - Day 14 | 
| Antibiotic type switches and de-escalation based on antimicrobial agent categories | Time to de-escalation and time to stop of anti-infective therapy | Day 1 - Day 14 | 
| 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. | Proportion of hospitalised participants with detection of cephalosporin-, carbapenem- or chinolone-resistant Enterobacteriaceae on any standard of care samples >7 days after randomisation | >7 days after randomisation | 
| Impact on decisions regarding isolation measures related to test result. | Hours in individual or cohort isolation in hospitalised participants | Day 1 - Day 30 |