Antimicrobial Stewardship for Ventilator Associated Pneumonia in Intensive Care (the ASPIC trial): study protocol for a randomised controlled trial

Abstract

Introduction: Ventilator-associated pneumonia (VAP) remains the leading cause of infections treated in the intensive care units (ICU). In a personalised care approach, we hypothesise that the duration of treatment of VAP can be reduced in function of the response to treatment.

Methods and analysis: The Antimicrobial Stewardship for Ventilator-Associated Pneumonia in Intensive Care (ASPIC) trial is a pragmatic national multicentre, phase III, non-inferiority, comparative randomised (1:1) single-blinded clinical trial. Five hundred and ninety adult patients hospitalised in 24 French ICU with a microbiologically confirmed first episode of VAP that received appropriate empirical antibiotic therapy will be included. They will be randomly allocated to standard management with duration of appropriate antibiotic fixed for 7 days according to international guidelines or antimicrobial stewardship based on daily clinical assessment of clinical cure. The assessment of clinical cure will be repeated daily until at least three criteria of clinical cure are met, allowing the discontinuation of antibiotic therapy in experimental group. The primary endpoint is a composite endpoint combining of all-cause mortality measured at day 28, treatment failure or new episode of microbiologically confirmed VAP until day 28.The aim of the study is to demonstrate that a strategy to reduce the duration of antibiotic therapy for VAP based on clinical assessment is safe could lead to changes in practice as part of a personalised therapeutic approach, by reducing exposure to antibiotics and their side effects.

Ethics and dissemination: The ASPIC trial has been approved by the French regulatory agency (Agence Nationale de Sécurité du Médicament et des Produits de Santé, ANSM; EUDRACT number 2021-002197-78, 19 August 2021) and an independent ethics committee the Comité de Protection des Personnes Ile-de-France III (CNRIPH : 21.03.25.60729, 10 October 2021) for the study protocol (version ASPIC-1.3; 03 September 2021) for all study centres. Participant recruitment is scheduled to begin in 2022. Results will be published in international peer-reviewed medical journals.

Trial registration number: NCT05124977.

Keywords: Adult intensive & critical care; Infection control; Respiratory infections.

Conflict of interest statement

Competing interests: AF, DB, AB, PE: declare no competing interest. AR: grants from bioMerieux and Merck. IM-L: board on PFIZER, MSD, GILEAD. J-FT directly related to the protocol: none, participation to scientific advisory boards: Pfizer, Gilead, Merck, BD, Shionoghi; readings: Merck, Biomerieux, Pfizer, Shionogi; research grants to my research unit: Thermo Fischer, Pfizer, Merck. J-RZ: consulting fees from MSD, Pfizer, speaker fees from MSD, Pfizer, Shionogi, Correvio and Eumedica. EW: Speaker fees from MSD, Akcea therapeutics and LFB, support for attending meeting/travel: LFB and Akcea therapeutics.

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

General flowchart of the study. VAP, ventilator-associated pneumonia.

Figure 2

Criteria of clinical cure and criteria for discontinuation of antibiotic therapy in experimental arm. *Compared to the day of initiation of antibiotic therapy. VAP: ventilator-associated pneumonia.

Figure 3

Description of microbiological categories of outcomes in relation to time of occurrence of new episode of VAP after inclusion adapted from Bai et al. VAP: ventilator-associated pneumonia.