Community-acquired Acute Lower Respiratory Infection Clinical Trial
Official title:
ADEQUATE Advanced Diagnostics for Enhanced QUality of Antibiotic Prescription in Respiratory Tract Infections in Emergency Rooms - Paediatric
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.
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. ;