search
Back to results

ADEQUATE Advanced Diagnostics for Enhanced QUality of Antibiotic Prescription in Respiratory Tract Infections in Emergency Rooms - Paediatric (ADEQUATE)

Primary Purpose

Community-acquired Acute Lower Respiratory Infection

Status
Recruiting
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
BioFire FilmArray Respiratory Panel 2.1 plus (RP2.1plus)
Sponsored by
PENTA Foundation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Community-acquired Acute Lower Respiratory Infection focused on measuring community-acquired pneumonia, point-of-care test, rapid diagnostics

Eligibility Criteria

0 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University Children's Hospital Basel (UKBB)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Intervention (Device)

Control (Standard of Care)

Arm Description

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

Standard of Care

Outcomes

Primary Outcome Measures

Days alive out of hospital (superiority endpoint), within 14 days
Days alive out of hospital (superiority endpoint), within 14 days
Days on Therapy (DOT) with antibiotics (superiority endpoint), within 14 days
Days on Therapy (DOT) with antibiotics (superiority endpoint), within 14 days
Adverse outcome (non-inferiority safety endpoint)
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

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
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.
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
Proportion of participants with an identified respiratory pathogen in both study groups on randomisation day samples.
Empirical antibiotics based on antimicrobial agent categories
Proportion of participants on non-first-line anti-infective regimens (as defined by local guidelines)
Antibiotic type switches and de-escalation based on antimicrobial agent categories
Time to de-escalation and time to stop of anti-infective therapy
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
Impact on decisions regarding isolation measures related to test result.
Hours in individual or cohort isolation in hospitalised participants

Full Information

First Posted
February 2, 2021
Last Updated
October 13, 2023
Sponsor
PENTA Foundation
Collaborators
BioMérieux, Universiteit Antwerpen, St George's, University of London
search

1. Study Identification

Unique Protocol Identification Number
NCT04781530
Brief Title
ADEQUATE Advanced Diagnostics for Enhanced QUality of Antibiotic Prescription in Respiratory Tract Infections in Emergency Rooms - Paediatric
Acronym
ADEQUATE
Official Title
ADEQUATE Advanced Diagnostics for Enhanced QUality of Antibiotic Prescription in Respiratory Tract Infections in Emergency Rooms - Paediatric
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 7, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PENTA Foundation
Collaborators
BioMérieux, Universiteit Antwerpen, St George's, University of London

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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 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 hospitalized patients: any readmission, ICU admission >= 24 hours after hospitalization or death, all within 30 days

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Community-acquired Acute Lower Respiratory Infection
Keywords
community-acquired pneumonia, point-of-care test, rapid diagnostics

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
The trial is unblinded / open-label.
Allocation
Randomized
Enrollment
900 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention (Device)
Arm Type
Experimental
Arm Description
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
Arm Title
Control (Standard of Care)
Arm Type
No Intervention
Arm Description
Standard of Care
Intervention Type
Device
Intervention Name(s)
BioFire FilmArray Respiratory Panel 2.1 plus (RP2.1plus)
Intervention Description
BioFire FilmArray Respiratory Panel 2.1 plus (RP2.1plus): Nasopharyngeal swab
Primary Outcome Measure Information:
Title
Days alive out of hospital (superiority endpoint), within 14 days
Description
Days alive out of hospital (superiority endpoint), within 14 days
Time Frame
14 days
Title
Days on Therapy (DOT) with antibiotics (superiority endpoint), within 14 days
Description
Days on Therapy (DOT) with antibiotics (superiority endpoint), within 14 days
Time Frame
14 days
Title
Adverse outcome (non-inferiority safety endpoint)
Description
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
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Direct costs and indirect costs within 30 days after enrolment.
Description
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
Time Frame
30 days
Title
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.
Description
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.
Time Frame
1, 14 and 30 days
Title
Microbiological results obtained as standard of care and with the diagnostic intervention
Description
Proportion of participants with an identified respiratory pathogen in both study groups on randomisation day samples.
Time Frame
Day 1
Title
Empirical antibiotics based on antimicrobial agent categories
Description
Proportion of participants on non-first-line anti-infective regimens (as defined by local guidelines)
Time Frame
Day 1 - Day 14
Title
Antibiotic type switches and de-escalation based on antimicrobial agent categories
Description
Time to de-escalation and time to stop of anti-infective therapy
Time Frame
Day 1 - Day 14
Title
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
Description
Proportion of hospitalised participants with detection of cephalosporin-, carbapenem- or chinolone-resistant Enterobacteriaceae on any standard of care samples >7 days after randomisation
Time Frame
>7 days after randomisation
Title
Impact on decisions regarding isolation measures related to test result.
Description
Hours in individual or cohort isolation in hospitalised participants
Time Frame
Day 1 - Day 30

10. Eligibility

Sex
All
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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: Development of ARTI more than 48 hours after hospital admission (hospital acquired); Patients with a severe underlying medical condition dictating management decisions including hospitalisation and/or antibiotic treatment (e.g cystic fibrosis, immunosuppression); Less than 14 days since the last episode of respiratory tract infection; Confirmed pregnancy and/or 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; Alternative noninfectious diagnosis that explains clinical symptoms.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Federica D'Ambrosio, MSc
Phone
3783029089
Email
federica.dambrosio@pentafoundation.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julia Bielicki, PhD
Organizational Affiliation
St George's, University of London
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Children's Hospital Basel (UKBB)
City
Basel
State/Province
Basel-Stadt
ZIP/Postal Code
4056
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bielicki, MD
Phone
+44 20 87 25 27 80
Email
JuliaAnna.Bielicki@ukbb.ch

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

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

We'll reach out to this number within 24 hrs