Clinical trial NCT04547556: ADEQUATE Advanced Diagnostics for Enhanced Quality of Antibiotic Prescription
Official title: ADEQUATE Advanced Diagnostics for Enhanced QUality of Antibiotic Prescription in Respiratory Tract Infections in Emergency Rooms
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Respiratory Tract Infections
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: BioMérieux
First posted: 2020-09-14
Enrollment: 185
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: Inclusion Criteria:

1. 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:
     1. to treat patient with antibiotics and/or to hospitalize patient

        AND
     2. 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:

1. Development of ARTI more than 48 hours after hospital admission (hospital acquired);
2. Patients with cystic fibrosis;
3. Less than 14 days since the last episode of respiratory tract infection;
4. Pregnancy (confirmed by pregnancy test) and 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 from a competent patient.

   Based on standard of care microbiological diagnosis and thoracic imaging (when indicated):
7. Radiologically confirmed acute lobar pneumonia;
8. Known or suspected Pneumocystis jirovecii pneumonia or active tuberculosis;
9. Alternative noninfectious diagnosis that explains clinical symptoms (pulmonary embolism, alveolar hemorrhage, acute heart failure, lung cancer).

Primary outcomes:
measure: Days Alive Out of Hospital (Superiority Endpoint)
timeFrame: Day 1 - Day 14
measure: Days on Therapy (DOT) With Antibiotics (Superiority Endpoint)
timeFrame: Day 1 - Day 14
measure: Adverse Outcome (Non-inferiority Safety Endpoint)
timeFrame: Day 1 - Day 30
Secondary outcomes:
measure: Direct Costs and Indirect Costs Within 30 Days After Enrolment.
timeFrame: Day 1 - Day 30
measure: Microbiological Results Obtained as Standard of Care and With the Diagnostic Intervention
timeFrame: Day 1
measure: Empirical Antibiotics Based on Antimicrobial Agent Categories
timeFrame: Day 1 - Day 14
measure: Antibiotic Type Switches and De-escalation Based on Antimicrobial Agent Categories
timeFrame: Day 1 - Day 14
measure: 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.
timeFrame: >7 days after randomisation
measure: Impact on Decisions Regarding Isolation Measures Related to Test Result.
timeFrame: Day 1 - Day 30
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: University Hospital Gent
city: Pecs
country: Hungary
facility: University Hospital Pecs
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Kragujevac
country: Serbia
facility: General Hospital Kragujevac
Study officials:
affiliation: UMC Utrecht
name: Marc Bonten, MD
role: PRINCIPAL_INVESTIGATOR
References: