Clinical trial NCT04153682: Trial on a Strategy Combining Rapid Diagnostic Testing and Antimicrobial Stewardship to Improve Antibiotic Use in Patients with Hospital-acquired Pneumonia.
Official title: Impact of a Strategy Combining the Rapid Polymerase Chain Reaction Platform FilmArray® and the Intervention of an Antimicrobial Stewardship Team in Hospital-acquired Pneumonia : a Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hospital-acquired Pneumonia
Keywords: Antimicrobial stewardship
hospital-acquired pneumonia
syndromic approach
rapid diagnostic testing
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2019-11-06
Enrollment: 116
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: Hospital-Acquired Pneumonia (HAP) is the second most frequent hospital-acquired infection in the US and Europe and accounts for a large proportion of antibiotics prescribed in hospitals. Conventional methods to identify causative microorganisms (virus, bacteria) are time-consuming and sometimes inaccurate, leading to inadequate treatment in a large proportion of HAP patients.

The FILMARRAY® Pneumonia Panel (FA-PP, bioMérieux) is an automated diagnostic device, allowing detection of multiple pathogens and resistance markers in one hour. Strategies combining rapid diagnostic testing and intervention of specialists in infectious diseases (i.e. antimicrobial stewardship -AMS - experts) showed significant synergistic impact on antibiotic use, mortality and costs in bloodstream infections.

The trial hypothesis is that a strategy combining antimicrobial stewardship and FA-PP improves quality of care in HAP patients, as compared to antimicrobial stewardship alone.

The trial will include patients hospitalized for ≥ 48 hours, aged 18 years or older, who have criteria of pneumonia: new lung infiltrate on a chest-x ray, plus evidence that the infiltrate is of an infectious origin (i.e. new onset of fever and/or purulent sputum and/or leukocytosis and/or decline in oxygenation).

After informed consent, participants will be randomly allocated to either the intervention or the control arm.

In the control arm, management of HAP patients will include clinical examination and conventional microbiological tests. Antibiotic choice will be discussed between AMS experts and the physician in charge of the patient.

In the intervention arm, in addition to the procedures above, the strategy will include rapid testing using the FA-PP on a respiratory specimen, obtained by either invasive or non-invasive sampling. No additional invasive procedures will be required for the study, and FA-PP will be performed on samples collected as part as routine care.

Investigators will visit the patient at inclusion, on day 3 and on day 30 (or at hospital discharge) to collect data on comorbidities, clinical outcomes, results of microbiological tests and antibiotics. At the end of follow-up, we will compare the number of days on broad-spectrum antibiotics, the incidence of negative outcomes, the length of stay and costs in the two arms.

The use of the FA-PP is expected to prompt early adjustment of antibiotic therapy, improve outcomes, decrease length of stay, and to reduce the use of broad-spectrum antibiotics. The antibiotic saving may reduce the selection pressure, incidence of colonization with multidrug-resistant bacteria and incidence of hospital-acquired superinfections, both at an individual and hospital level. Moreover, this trial relies on the intervention of multidisciplinary AMS teams that are currently being implemented in many health facilities. Their transversal position offers opportunities for recruitment of patients from a wide range of medical and surgical departments. This project evaluates the feasibility of clinical trials based on the intervention of these teams, and will provide a high level of evidence regarding their impact on the prognosis of patients, appropriate use of antibiotics, and antimicrobial resistance.


Eligibility criteria: Inclusion Criteria:

* Any patient hospitalized for ≥ 48 hours
* aged 18 years or older
* not mechanically-ventilated at time of onset of pneumonia symptoms
* Dated and signed inform consent - written informed consent of relative (trusted person, close family) in case of emergency procedure, by default emergency inclusion notified in medical file and pursuance consent sought
* Affiliation with a social security scheme

Criteria of pneumonia:

* New lung infiltrate on a chest-x ray plus
* Evidence that the infiltrate is of an infectious origin, i.e. new onset of fever (\> 38.5°C) and/or purulent sputum and/or leukocytosis and/or decline in oxygenation

Exclusion Criteria:

* Patients with severe chronic bronchitis structural changes: very severe COPD (Global initiative for chronic Obstructive Lung Disease GOLD 4), cystic fibrosis
* Radiological evidence of thoracic empyema, pulmonary abcess
* Patient life expectancy \< 90 days

Primary outcomes:
measure: Number of days on broad-spectrum antibiotics at day 30 or end-of follow-up for 100 patients-days
timeFrame: Day 30 or hospital discharge (plus or minus 4 days)
Secondary outcomes:
measure: Overall antibiotic use
timeFrame: Day 30 or hospital discharge (plus or minus 4 days)
measure: Duration of antibiotics for the HAP episode
timeFrame: up to 30 days
measure: Mortality
timeFrame: up to 30 days
measure: In-hospital length of stay
timeFrame: up to 24 weeks
measure: Incidence of Clostridium difficile colitis
timeFrame: Day 30 or hospital discharge (plus or minus 4 days)
measure: Medical direct costs
timeFrame: Day 30 or hospital discharge (plus or minus 4 days)
measure: Analytical performances of the FILMARRAY® Pneumonia panel compared to conventional methods
timeFrame: End of the study
Other outcomes:
Locations:
city: Créteil
country: France
facility: Hôpitaux Universitaires Henri Mondor
city: Nancy
country: France
facility: CHRU Nancy
city: Paris
country: France
facility: Hôpitaux Universitaires Paris Centre (Cochin) - service Médecine Intensive - Réanimation
city: Paris
country: France
facility: Groupe Hospitalier Paris Saint Joseph
city: Paris
country: France
facility: Hôpitaux Universitaires Paris Centre-Site Cochin
city: Paris
country: France
facility: Hôpitaux Universitaires Paris Nord Val de Seine-Site Bichat (SMIT)
city: Paris
country: France
facility: Hôpitaux Universitaires Paris Nord Val de Seine - EPRI (Bichat)
city: Paris
country: France
facility: Hôpitaux Universitaires Paris Nord Val de Seine - MIR (Bichat)
Study officials:
affiliation: Antimicrobial Stewardship Team, Hôpitaux Universitaires Paris Centre, Université de Paris
name: Solen Kernéis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Bookstaver PB, Nimmich EB, Smith TJ 3rd, Justo JA, Kohn J, Hammer KL, Troficanto C, Albrecht HA, Al-Hasan MN. Cumulative Effect of an Antimicrobial Stewardship and Rapid Diagnostic Testing Bundle on Early Streamlining of Antimicrobial Therapy in Gram-Negative Bloodstream Infections. Antimicrob Agents Chemother. 2017 Aug 24;61(9):e00189-17. doi: 10.1128/AAC.00189-17. Print 2017 Sep.
citation: Kerneis S, Visseaux B, Armand-Lefevre L, Timsit JF. Molecular diagnostic methods for pneumonia: how can they be applied in practice? Curr Opin Infect Dis. 2021 Apr 1;34(2):118-125. doi: 10.1097/QCO.0000000000000713.