Antimicrobial Stewardship For Ventilator Associated Pneumonia in Intensive Care

NCT ID: NCT05124977

Last Updated: 2025-05-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 590 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-20
• Study Completion Date: 2026-03-31

Brief Summary

Increasing emergence of multidrug resistant (MDR) bacteria worldwide is now considered one of the most urgent threats to global health. The association between increase of antibiotics consumption and resistance emergence has been well documented for all patients admitted to the Intensive care unit (ICU) who received antibiotic treatment and for patients treated for ventilator associated pneumonia (VAP).

Reduction of use of antibiotics is a major point in the war against antimicrobial resistance. VAP is the first cause of healthcare-associated infections in ICU and more than half of antibiotics prescriptions in ICU are due to VAP.

Once the diagnosis of pneumonia under MV has been made, initiation of antibiotic treatment must be prompt but there is no clear consensus on its duration. In the case of a good clinical response to treatment, it has been shown in some situations that short course antibiotics can be effective without side effects and antimicrobial stewardship initiatives can be applied successfully and effectively to the management of Community Acquired Pneumonia (CAP).

The hypothesis is that an antimicrobial stewardship is possible in the treatment of VAP with no increase in the rate of all-cause mortality, treatment failure or occurrence of new episode of pneumonia.

The objective is to investigate whether an antimicrobial stewardship for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would be non-inferior in terms of all-cause mortality, treatment failure or occurrence of new episode of pneumonia.

This study will be a prospective, national multicenter (31 centers), phase III, comparative randomized (1:1), single-blinded clinical trial comparing two management strategies of treatment of pneumonia on the basis of two parallel arms:

Experimental group: Antimicrobial stewardship based on daily clinical assessment of clinical cure.

Control group: standard management: duration of appropriate antibiotic therapy for confirmed VAP according to guidelines.

Detailed Description

Increasing emergence of multidrug resistant (MDR) bacteria worldwide is now considered one of the most urgent threats to global health. The association between increase of antibiotics consumption and resistance emergence has been well documented for all patients admitted to the Intensive care unit (ICU) who received antibiotic treatment1 and for patients treated for ventilator associated pneumonia (VAP). Reduction of use of antibiotics is a major point in the war against antimicrobial resistance. VAP is the first cause of healthcare-associated infections in ICU and more than half of antibiotics prescriptions in ICU are due to VAP. Current international guidelines define VAP as a pneumonia occurring>48 hours after endotracheal intubation and distinguishes early onset VAP occurring in the first five days after admission and late VAP, occurring after.

Once the diagnosis of pneumonia under MV has been made, initiation of antibiotic treatment must be prompt but there is no clear consensus on its duration. In the case of a good clinical response to treatment, it has been shown in some situations that short course antibiotics can be effective without side effects and antimicrobial stewardship initiatives can be applied successfully and effectively to the management of Community Acquired Pneumonia (CAP).

American guidelines strongly recommend a 7-day course of antibiotic therapy rather than a longer duration but remark that "there exist situations in which a shorter or longer duration of antibiotics may be indicated, depending upon the rate of improvement of clinical, radiologic, and laboratory parameters".

The hypothesis is that an antimicrobial stewardship is possible in the treatment of VAP with no increase in the rate of all-cause mortality, treatment failure or occurrence of new episode of pneumonia.

The objective is to investigate whether an antimicrobial stewardship for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would be non-inferior in terms of all-cause mortality, treatment failure or occurrence of new episode of pneumonia.

This study will be a prospective, national multicenter (31 centers), phase III, comparative randomized (1:1), single-blinded clinical trial comparing two management strategies of treatment of pneumonia on the basis of two parallel arms:

Experimental group: Antimicrobial stewardship based on daily clinical assessment of clinical cure.

Control group: standard management: duration of appropriate antibiotic therapy for confirmed VAP according to guidelines.

The primary endpoint is a hierarchical endpoint with a first non-inferiority criteria and a second efficacy criteria.

Conditions

Ventilator Associated Pneumonia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: SINGLE

Study Groups

Experimental group

Antimicrobial stewardship based on daily clinical assessment of clinical cure (experimental group). Discontinuation of antibiotic therapy antibiotics if criterions of clinical cure (regression of tracheal secretions, regression of temperature, improvement of PaO2/FiO2 ratio, absence of hemodynamic failure) of confirmed VAP are met. In the intervention group, intensivists will perform clinical assessment daily in order to decide on the pursuit or discontinuation of antibiotic therapy.

Group Type: EXPERIMENTAL

Antimicrobial Stewardship

Intervention Type: DRUG

Antimicrobial stewardship based on daily clinical assessment of clinical cure. Discontinuation of appropriate antibiotic therapy antibiotics if criteria of clinical cure of confirmed pneumonia are met. Intensivists will perform clinical assessment daily in order to decide on the pursuit or discontinuation of antibiotic therapy.

Control group

Standard management: duration of appropriate antibiotic therapy for confirmed VAP according to guidelines. In the control group, intensivists will perform clinical assessment daily, but a minimum duration of 7 days, as highly recommended of antibiotic therapy will be mandatory whatever the clinical cure.

Group Type: OTHER

Standard management

Intervention Type: DRUG

Standard management: duration of appropriate antibiotic for confirmed pneumonia fixed for 7 days according to guidelines. In the control group, intensivists will perform clinical assessment daily, but the antibiotic will not be discontinued until 7 days whatever the clinical cure.

Interventions

Antimicrobial Stewardship

Antimicrobial stewardship based on daily clinical assessment of clinical cure. Discontinuation of appropriate antibiotic therapy antibiotics if criteria of clinical cure of confirmed pneumonia are met. Intensivists will perform clinical assessment daily in order to decide on the pursuit or discontinuation of antibiotic therapy.

Intervention Type: DRUG

Standard management

Standard management: duration of appropriate antibiotic for confirmed pneumonia fixed for 7 days according to guidelines. In the control group, intensivists will perform clinical assessment daily, but the antibiotic will not be discontinued until 7 days whatever the clinical cure.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosis of microbiologically confirmed of first episode of VAP
• Initial appropriate antibiotic therapy (whether empirical or not)
• Written informed consent from the patient or a legal representative if appropriate. If absence of a legal representative the patient may be included in emergency procedure

Definitive diagnosis of pneumonia (in agreement with international guidelines) is defined by association:

• Patient under MV>48 hours at the time of the microbiological sampling
• New pulmonary infiltrate of which an infectious origin is strongly suspected
• Worsening oxygenation
• Have the following clinical criteria within the 24 hours prior to the first dose of antibiotic therapy

• Purulent tracheal secretions
• And at least 1 of the following : documented fever (body temperature >38,3°C) or hypothermia (body temperature <35°C) or white blood cell (WBC) count >10,000 cells/mm3 or <4,000 cells/mm3
• Microbiological criteria (positive quantitative culture of a lower respiratory tract (LRT): bronchoalveolar lavage fluid (BAL) (significant threshold ≥10^4 colony-forming units/mL) or plugged telescopic catheter (PTC) (significant threshold ≥ 10^3 colony-forming units/mL) or quantitative endotracheal aspirate (ETA) distal pulmonary secretion samples (significant threshold ≥10^5 colony-forming units/mL)

Exclusion Criteria

• Patient under selective decontamination of the digestive tract
• Duration of antibiotic therapy prior to inclusion > 72h (for any reason) appropriate to the germs found in the bacterial documentation of the first episode of VAP
• Inclusion in another interventional study concerning antimicrobial strategies
• Moribund (IGS II>80)
• Thoracic trauma with Abbreviated Injury Scale (AIS) thorax ≥ 3
• Severely immunocompromised patients (such as congenital immunodeficiency, neutropenia (<1leucocyte/ml or <0.5 neutrophil/ml) or acute hematologic malignancy or stem cell transplant, HIV infection with CD4 count below 200/mm3
• Patients undergoing immunosuppressive therapy and long term corticotherapy > 0.5 mg/kg
• VAP due to: Pseudomonas aeruginosa, Carbapenem-resistant Acinetobacter spp, Carbapenem-resistant Enterobacteriaceae
• VAP occurring in the context of co-infection of COVID-19 or other viral pneumonia (confirmed by RT-PCR)
• Patients with empyema, necrotizing and abscessed pneumonia
• Patients requiring extracorporeal oxygen therapy (ECMO), either veno-venous or veno-arterial
• Pregnant women
• No health insurance coverage

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arnaud Foucrier

Role: PRINCIPAL_INVESTIGATOR

APHP

Locations

Foucrier

Clichy-sous-Bois, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Arnaud Foucrier

Role: CONTACT

arnaud.foucrier@aphp.fr

+33 1 40 87 52 33

Emmanuel Weiss

Role: CONTACT

emmanuel.weiss@aphp.fr

+33 1 40 87 59 11

Facility Contacts

Arnaud Foucrier

Role: primary

arnaud.foucrier@aphp.fr

140875911 ext. 33

References

Foucrier A, Roquilly A, Bachelet D, Martin-Loeches I, Bougle A, Timsit JF, Montravers P, Zahar JR, Eloy P, Weiss E; ASPIC study group. Antimicrobial Stewardship for Ventilator Associated Pneumonia in Intensive Care (the ASPIC trial): study protocol for a randomised controlled trial. BMJ Open. 2023 Feb 21;13(2):e065293. doi: 10.1136/bmjopen-2022-065293.

Reference Type: DERIVED

PMID: 36810173 (View on PubMed)

Other Identifiers

APHP200011

Identifier Type: -

Identifier Source: org_study_id