Trial on a Strategy Combining Rapid Diagnostic Testing and Antimicrobial Stewardship to Improve Antibiotic Use in Patients With Hospital-acquired Pneumonia.

Hospital-acquired Pneumonia Clinical Trial

— SHARP  

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 in Non-mechanically Ventilated Patients: a Randomized Controlled Trial.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04153682
• Other study ID #: APHP180391
• Status: Recruiting
• Phase: N/A
• Start date: February 21, 2020
• Est. completion date: March 21, 2023

Study information

• Verified date: October 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Solen Kernéis, MD, PhD
• Phone: +33 1 58.41.19.08
• Email: solen.kerneis[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: March 21, 2023
• Est. primary completion date: February 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Any patient hospitalized for = 48 hours

• aged 18 years or older

• not mechanically-ventilated at inclusion

• with criteria of pneumonia

• 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), tracheostomy, bronchiectasis, cystic fibrosis

• Radiological evidence of thoracic empyema, pulmonary abcess

• Patient life expectancy < 90 days

Related Conditions & MeSH terms

• Healthcare-Associated Pneumonia
• Hospital-acquired Pneumonia
• Pneumonia

Intervention

Diagnostic Test:
• Rapid Diagnostic Testing
Automated microbiological diagnostic device based on multiplex PCR analysis, allowing detection of multiple pathogens and resistance markers in one hour from invasive and non-invasive respiratory samples
• Antimicrobial stewardship
After clinical examination, routine biological tests will be performed. This includes blood culture, direct examination and culture of invasive or noninvasive respiratory samples, urinary antigen tests for Legionella and Pneumococcus, Influenza PCR on nasopharyngeal swabs (during the influenza season).

Locations

Country	Name	City	State
France	Hôpitaux Universitaires Henri Mondor	Créteil
France	CHRU Nancy	Nancy
France	Groupe Hospitalier Paris Saint Joseph	Paris
France	Hôpitaux Universitaires Paris Centre (Cochin) - service Médecine Intensive - Réanimation	Paris
France	Hôpitaux Universitaires Paris Centre-Site Cochin	Paris
France	Hôpitaux Universitaires Paris Nord Val de Seine - EPRI (Bichat)	Paris
France	Hôpitaux Universitaires Paris Nord Val de Seine - MIR (Bichat)	Paris
France	Hôpitaux Universitaires Paris Nord Val de Seine-Site Bichat (SMIT)	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (5)

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). pii: e00189-17. doi: 10.1128/AAC.00189-17. Print 2017 Sep. — View Citation

Davey P, Marwick CA, Scott CL, Charani E, McNeil K, Brown E, Gould IM, Ramsay CR, Michie S. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev. 2017 Feb 9;2:CD003543. doi: 10.1002/14651858.CD003543.pub4. Review. — View Citation

Gadsby NJ, Russell CD, McHugh MP, Mark H, Conway Morris A, Laurenson IF, Hill AT, Templeton KE. Comprehensive Molecular Testing for Respiratory Pathogens in Community-Acquired Pneumonia. Clin Infect Dis. 2016 Apr 1;62(7):817-823. doi: 10.1093/cid/civ1214. Epub 2016 Jan 7. — View Citation

Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, Napolitano LM, O'Grady NP, Bartlett JG, Carratalà J, El Solh AA, Ewig S, Fey PD, File TM Jr, Restrepo MI, Roberts JA, Waterer GW, Cruse P, Knight SL, Brozek JL. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016 Sep 1;63(5):e61-e111. doi: 10.1093/cid/ciw353. Epub 2016 Jul 14. Erratum in: Clin Infect Dis. 2017 May 1;64(9):1298. Erratum in: Clin Infect Dis. 2017 Oct 15;65(8):1435. Clin Infect Dis. 2017 Nov 29;65(12):2161. — View Citation

Messika J, Stoclin A, Bouvard E, Fulgencio JP, Ridel C, Muresan IP, Boffa JJ, Bachmeyer C, Denis M, Gounant V, Esteso A, Loi V, Verdet C, Prigent H, Parrot A, Fartoukh M. The Challenging Diagnosis of Non-Community-Acquired Pneumonia in Non-Mechanically Ventilated Subjects: Value of Microbiological Investigation. Respir Care. 2016 Feb;61(2):225-34. doi: 10.4187/respcare.04143. Epub 2015 Dec 8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of days on broad-spectrum antibiotics at day 30 or end-of follow-up for 100 patients-days	Number of days that a patient is on an antibiotic, regardless of dose. The list of broad-spectrum antibiotics was defined according to previous literature data.	Day 30 or hospital discharge (plus or minus 4 days)
Secondary	Overall antibiotic use	Number of days on antibiotics per 100 patient-days	Day 30 or hospital discharge (plus or minus 4 days)
Secondary	Duration of antibiotics for the HAP episode	Number of days on any antibiotic for the HAP episode	up to 30 days
Secondary	Mortality		up to 30 days
Secondary	In-hospital length of stay	Number of days between admission and discharge	up to 24 weeks
Secondary	Incidence of Clostridium difficile colitis	Number of patients with documented Clostridium difficile colitis per 100 patient-days.; Clostridium difficile colitis is defined by clinical evidence of colitis (unexplained and new-onset =3 unformed stools) and positive microbiological test relying on the multistep algorithm routinely used in each investigating center and compliant with national and international standards.	Day 30 or hospital discharge (plus or minus 4 days)
Secondary	Medical direct costs	Costs of the FILMARRAY® Pneumonia panel (labor and consumables), Antibiotic costs, Total admission costs	Day 30 or hospital discharge (plus or minus 4 days)
Secondary	Analytical performances of the FILMARRAY® Pneumonia panel compared to conventional methods	Number of discrepancies on Micro-organism identification and Antibiotic resistance	End of the study