Inhaled amikacin versus placebo to prevent ventilator-associated pneumonia: the AMIKINHAL double-blind multicentre randomised controlled trial protocol

Tavernier, Elsa; Barbier, Francois; Meziani, Ferhat; Quenot, Jean-Pierre; Herbrecht, Jean-Etienne; Landais, Mickael; Roux, Damien; Seguin, Philippe; Schnell, David; Veinstein, Anne; Veber, Benoît; Lasocki, Sigismond; Lu, Qin; Beduneau, Gaetan; Ferrandiere, Martine; Dahyot-Fizelier, Claire; Plantefeve, Gaetan; Nay, Mai-Anh; Merdji, Hamid; Andreu, Pascal; Vecellio, Laurent; Muller, Grégoire; Cabrera, Maria; Le Pennec, Deborah; Respaud, Renaud; Lanotte, Philippe; Gregoire, Nicolas; Leclerc, Marie; Helms, Julie; Boulain, Thierry; Lacherade, Jean-Claude; Ehrmann, Stephan

INTRODUCTION: Pre-emptive inhaled antibiotics may be effective to reduce the occurrence of ventilator-associated pneumonia among critically ill patients. Meta-analysis of small sample size trials showed a favourable signal. Inhaled antibiotics are associated with a reduced emergence of antibiotic resistant bacteria. The aim of this trial is to evaluate the benefit of a 3-day course of inhaled antibiotics among patients undergoing invasive mechanical ventilation for more than 3 days on the occurrence of ventilator-associated pneumonia. METHODS AND ANALYSIS: Academic, investigator-initiated, parallel two group arms, double-blind, multicentre superiority randomised controlled trial. Patients invasively ventilated more than 3 days will be randomised to receive 20 mg/kg inhaled amikacin daily for 3 days or inhaled placebo (0.9% Sodium Chloride). Occurrence of ventilator-associated pneumonia will be recorded based on a standardised diagnostic framework from randomisation to day 28 and adjudicated by a centralised blinded committee. ETHICS AND DISSEMINATION: The protocol and amendments have been approved by the regional ethics review board and French competent authorities (Comité de protection des personnes Ouest I, No.2016-R29). All patients will be included after informed consent according to French law. Results will be disseminated in international scientific journals. TRIAL REGISTRATION NUMBERS: EudraCT 2016-001054-17 and NCT03149640.