Nebulised Colistimethate Sodium to Prevent Pediatric Ventilator-associated Pneumonia

Nebulised Colistimethate Sodium to Prevent Pediatric Ventilator-associated Pneumonia: The COLIPED Investigation

The goal of this clinical trial is to learn if nebulized colistimethate sodium can prevent pneumonia in ventilated children. The main question it aims to answer is:

• Does nebulized colistimethate sodium lower the number of times participants develop ventilation associated pneumonia? Researchers will compare nebulized colistimethate sodium to a placebo (a look-alike substance that contains no drug) to see if nebulized colistin works to prevent ventilation associated pneumonia in children.

Participants will:

• Take nebulized colistimethate sodium or a placebo twice a day for a maximum of 7 days.
• Will be followed to check for pneumonia occurrence while they are on mechanical ventilation.

The COLIPED investigation is made of phase I (COLIPED I), phase II (COLIPED II) and phase III (COLIPED III) trials. COLIPED I is a monocenter prospective observational study aimed at assessing the clinical tolerance of nebulised CMS administered over 3 to 7 days at high doses to infants and children less than 14-year old. COLIPED II and III are double-blind, multicenter randomised controlled trials. Patients on mechanical ventilation for more than 2 days will be randomized to receive inhaled colistimethate sodium twice daily for 3 days or inhaled placebo (0.9% Sodium Chloride). Primary outcome will be the occurrence of ventilator-associated pneumonia from randomization to day 28.COLIPED II will be conducted in PICUs with VAP prevalance greater than 20%, COLIPED III will be conducted in PICUs with VAP prevalence ranging between 10 to 20%

Inclusion Criteria:

• Children older than 1 month and younger than 14 years
• Patients on invasive mechanical ventilation for more than 48 hours
• Informed parental consent

Exclusion Criteria:

• Suspected or confirmed VAP on the day of inclusion
• Indication for systemic colistin therapy before or at enrolment in the study
• Plan for extubation within the next 24H
• Known allergy to colistin
• No parental consent
• Tracheostomy
• Appearance of allergic clinical manifestations in the days of colistin nebulization
• Appearance of undesirable clinical or biological manifestations presumed attributable to nebulization with colistin