Antimicrobial Stewardship For Ventilator Associated Pneumonia in Intensive Care

NCT05124977 | Recruiting

• 1 other identifier: APHP200011
• Study Type: interventional
• Target: 590
• Locations: 1 country
• Sites: 1

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.

Conditions

Ventilator Associated Pneumonia

Outcome Measures

Primary Outcomes (3)

• Investigate whether an AMS 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

  The primary endpoint is a composite endpoint with non-inferiority criteria including: 1\. all-cause mortality (ACM) measured at day 28 after initiation of therapy

  28 days

• Investigate whether an AMS 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

  The primary endpoint is a composite endpoint with non-inferiority criteria including: 2\. Treatment failure defined by new signs of pneumonia within 72 hours after the end antibiotic treatment at the test of cure visit

  28 days

• Investigate whether an AMS 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

  The primary endpoint is a composite endpoint with non-inferiority criteria including: 3\. New episode of microbiologically confirmed VAP from 72H after the end of antibiotic treatment to day 28 after initiation of VAP antibiotic treatment

  28 days

Secondary Outcomes (14)

• Investigate whether an AMS for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would be non-inferior in term of all-cause mortality

  28 days after inclusion

• Investigate whether an AMS for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would be non-inferior in term of occurrence of treatment failure

  28 days after inclusion

• investigate whether an AMS for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would be non-inferior in term of occurrence of new episode of pneumonia

  28 days after inclusion

• Investigate whether an AMS for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would increase the number of antibiotic free-alive days, from initiation of VAP antibiotic therapy to day 28

  28 days after inclusion

• Investigate whether an AMS for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would reduce at day 28 after inclusion of VAP antibiotic therapy the global DOOR score

  28 days after inclusion

Study Arms (2)

Experimental group

EXPERIMENTAL

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.

Drug: Antimicrobial Stewardship

Control group

OTHER

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.

Drug: Standard management

Interventions

Antimicrobial Stewardship 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.

Experimental group

Standard management 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.

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• Patient under selective decontamination of the digestive tract
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Foucrier

Clichy-sous-Bois, France

RECRUITING

Related Publications (1)

• 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.

  PMID: 36810173 DERIVED

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated

Interventions

Antimicrobial Stewardship

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Drug Utilization Review; Drug Utilization; Pharmacy Administration; Organization and Administration; Health Services Administration; Utilization Review; Quality of Health Care; Quality Assurance, Health Care; Health Care Quality, Access, and Evaluation

Study Officials

• Arnaud Foucrier

  APHP

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Arnaud Foucrier

CONTACT

+33 1 40 87 52 33; arnaud.foucrier@aphp.fr

Emmanuel Weiss

CONTACT

+33 1 40 87 59 11; emmanuel.weiss@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2021
• First Posted: November 18, 2021
• Study Start: September 20, 2022
• Primary Completion: September 1, 2025
• Study Completion: March 1, 2026
• Last Updated: May 25, 2025

Record last verified: 2025-05

Locations

FR (1)