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

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.