Clinical trial NCT06488794: Inhaled Colistin to Prevent Pediatric Ventilator-associated Pneumonia
Official title: Inhaled Colistin to Prevent Pediatric Ventilator-associated Pneumonia: A Double Blind Multicenter Randomized Controlled Trial Protocol
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Ventilator Associated Pneumonia
Keywords: colistin
mechanical ventilation
pneumonia
nebulization
prevention
pediatrics
Lead sponsor: University Hospital Fattouma Bourguiba
Sponsor class: OTHER
First posted: 2024-07-05
Enrollment: 400
Sex: ALL
Minimum age (years): 1
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: The aim of the study is to evaluate the benefit of a 3 to 7 day course of inhaled colistimethate sodium among children undergoing invasive mechanical ventilation for more than 2 days on the occurrence of ventilator-associated pneumonia.

A double-blind, multicenter randomized controlled trial will be conducted. Patients on mechanical ventilation for more than 2 days will be randomized to receive inhaled colistin 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Ventilation Associated Pneumonia
timeFrame: From randomization to 28 days post-randomization
Secondary outcomes:
measure: Incidence of Ventilation Associated Tracheobronchitis
timeFrame: From randomization to 28 days post-randomization
measure: Incidence of a first episode of VAP and VAT in the subgroup of patients with tracheobronchial bacterial colonization at randomization
timeFrame: From randomization to 28 days post-randomization
measure: Number of days spent on mechanical ventilation from randomization to day 28
timeFrame: From randomization to 28 days post-randomization
measure: Number of days without systemic antibiotics from randomization to day 28
timeFrame: From randomization to 28 days post-randomization
measure: ICU stay
timeFrame: From randomization to ICU discharge, up to 60 days
measure: Incidence of antibiotic-resistant bacteria
timeFrame: From randomization to ICU discharge
measure: ICU day-28 mortality
timeFrame: 28 days from ICU admission
Other outcomes:
Locations:
Study officials:
References:
citation: Zhu Y, Monsel A, Roberts JA, Pontikis K, Mimoz O, Rello J, Qu J, Rouby JJ; European Investigator Network for Nebulized Antibiotics in Ventilator-Associated Pneumonia (ENAVAP). Nebulized Colistin in Ventilator-Associated Pneumonia and Tracheobronchitis: Historical Background, Pharmacokinetics and Perspectives. Microorganisms. 2021 May 27;9(6):1154. doi: 10.3390/microorganisms9061154.
citation: Jang JY, Kwon HY, Choi EH, Lee WY, Shim H, Bae KS. Efficacy and toxicity of high-dose nebulized colistin for critically ill surgical patients with ventilator-associated pneumonia caused by multidrug-resistant Acinetobacter baumannii. J Crit Care. 2017 Aug;40:251-256. doi: 10.1016/j.jcrc.2017.04.004. Epub 2017 Apr 7.
citation: Karvouniaris M, Makris D, Zygoulis P, Triantaris A, Xitsas S, Mantzarlis K, Petinaki E, Zakynthinos E. Nebulised colistin for ventilator-associated pneumonia prevention. Eur Respir J. 2015 Dec;46(6):1732-9. doi: 10.1183/13993003.02235-2014. Epub 2015 Sep 24.
citation: Povoa FCC, Cardinal-Fernandez P, Maia IS, Reboredo MM, Pinheiro BV. Effect of antibiotics administered via the respiratory tract in the prevention of ventilator-associated pneumonia: A systematic review and meta-analysis. J Crit Care. 2018 Feb;43:240-245. doi: 10.1016/j.jcrc.2017.09.019. Epub 2017 Sep 18.