ADEQUATE Advanced Diagnostics for Enhanced Quality of Antibiotic Prescription

Not Applicable

Terminated

Conditions: Respiratory Tract Infections

Interventions: Diagnostic Test: BioFire

Registration Number: NCT04547556

Lead Sponsor: UMC Utrecht

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.

Detailed Description: Objective: 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) antibiotic 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.

Study design: Prospective, multi-center, individually randomised, controlled trial.

Study population: Adults (≥18 years old) consulting in selected participating sites with CA-ARTI.

Study Intervention: The diagnostic intervention is rapid syndromic testing with:

* BioFire FilmArray Pneumonia Panel plus (PP): Sputum (and/or ETA or BAL sample)

* BioFire FilmArray Respiratory Panel 2.1 plus (RP2.1plus): Nasopharyngeal swab

Main study parameters/endpoints:

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

* Days on Therapy (DOT) with antibiotics (superiority endpoint), within 14 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 within 30 days Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participation in the study involves collection of data that can be obtained from medical charts and follow up questionnaires and interviews. Respiratory samples (e.g. nasopharyngeal swab, sputum) will be obtained as standard of care and diagnostic intervention (Biofire FilmArray) will be used only for participants randomised to the intervention,Based on the results of diagnostic testing (BioFire FilmArray) antibiotics may be withheld when deemed unnecessary, or a different antibiotic class may be selected when certain bacterial pathogens are detected. The risks and benefits of management decisions, complemented with adequate training, are subject to the current investigation.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 185

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).
  1. Managing medical team considers:
  2. to treat patient with antibiotics and/or to hospitalize patient
    
    AND
  3. 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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	BioFire	-

Primary Outcome Measures

Name	Time	Method
Days Alive Out of Hospital (Superiority Endpoint)	Day 1 - Day 14	Days alive out of hospital (superiority endpoint), within 14 days after study enrolment
Days on Therapy (DOT) With Antibiotics (Superiority Endpoint)	Day 1 - Day 14	Days on Therapy (DOT) with antibiotics (superiority endpoint), within 14 days after study enrolment
Adverse Outcome (Non-inferiority Safety Endpoint)	Day 1 - Day 30	* For initially non-admitted patients: any admission or death * For initially hospitalized patients: any readmission, ICU admission \>= 24 hours after hospitalization, or death

Secondary Outcome Measures

Name	Time	Method
Direct Costs and Indirect Costs Within 30 Days After Enrolment.	Day 1 - Day 30	* 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
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. Data refers to the number of participants so in case more than one microorganism is detected in the same sample (co-detection) or same result in more than one sample, it is still counted as one participant.
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). For this report, results are defined as non first-line if the choice includes a third or fourth generation cephalosporin or a carbapenem but analysis needs to be adjusted to baseline risk factors, comorbidities, local guidelines and time to de escalation.
Antibiotic Type Switches and De-escalation Based on Antimicrobial Agent Categories	Day 1 - Day 14	For this report is presented the number of patients where the antimicrobial was switched to narrower spectrum.
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 comparing diagnostic intervention arm and standard of care arm.
Impact on Decisions Regarding Isolation Measures Related to Test Result.	Day 1 - Day 30	Hours in individual or cohort isolation in hospitalised participants comparing the 2 groups

Trial Locations

Locations (4): University Hospital Gent
🇧🇪
Gent, Belgium
University Hospital Pecs
🇭🇺
Pecs, Hungary
Clinical Center of Serbia
🇷🇸
Belgrade, Serbia
General Hospital Kragujevac
🇷🇸
Kragujevac, Serbia