Nebulised Colistimethate Sodium to Prevent Pediatric Ventilator-associated Pneumonia (ColiPed)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Ventilator Associated Pneumonia
• Intervention / Treatment: Drug: colistimethate sodium; Drug: 0.9% Saline

Detailed Description

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%

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Farah C Thabet, MD; Phone Number: 0021629742011; Email: thabetfarah@yahoo.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: colistin group; Colistin group: In the Nebulized colistimethate sodium (CMS) group, 100 000 IU/kg of CMS (equivalent to 0.96 mg/kg of colistin base), will be nebulized daily, divided into two doses. The lyophilisate of CMS will be reconstituted as follows: 2 million of IU is reconstituted in 6mL of sterile 0.9% saline. The adequate volume is then withdrawn and compleated by 0.9% saline to reach a total volume of 6 ml that is administered immediately to mechanically ventilated patients via a nebulizer until the nebulized solution container becomes empty. The nebulization is administered from day 3 of invasive mechanical ventilation, twice daily for a maximum of 7 days or until extubation (whichever occurres first). *12500 International Units of colistimethate sodium = 1 mg colistimethate sodium = 0.4 mg of colistin base.	Drug: colistimethate sodium; 100 000 IU/kg of colistimethate sodium (equivalent to 0.96 mg/kg of colistin base) , will be nebulized daily, divided into two doses for a maximum of 7 days for eligible ventilated children starting from day 3 of mechanical ventilation.; Other Names: Colistin
Placebo Comparator: Control group; Nebulization of 6 ml of 0.9% saline twice a day for a maximum of 7 days from day 3 of invasive mechanical ventilation will be administered via a nebulizer until the nebulized solution container becomes empty.	Drug: 0.9% Saline; Nebulization of 6 ml of 0.9% saline twice a day for a maximum of 7 days from day 3 of invasive mechanical ventilation for eligibile ventilated children; Other Names: normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Ventilation Associated Pneumonia	Primary outcome will be the incidence of a first episode of ventilation associated pneumonia from randomization to day 28. Incidence will be calculated as the ratio of the number of patients experiencing a first VAP episode divided by the number of randomized patients	From randomization to 28 days post-randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Ventilation Associated Tracheobronchitis	Incidence of first episode of ventilation associated tracheobronchitis (VAT) from randomization to day 28.	From randomization to 28 days post-randomization
Incidence of a first episode of VAP and VAT in the subgroup of patients with tracheobronchial bacterial colonization at randomization	This secondary outcome measures the incidence of the first episode of ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT) within the first 28 days post-randomization in patients who had tracheobronchial bacterial colonization at the time of randomization. The 28-day period is selected to capture early occurrences of these infections and to evaluate the effectiveness of preemptive colistin nebulization in this high-risk subgroup.	From randomization to 28 days post-randomization
Number of days spent on mechanical ventilation from randomization to day 28	This secondary outcome measures the total number of days a patient remains on mechanical ventilation within the first 28 days following randomization. The 28-day period is chosen to assess the impact of preemptive colistin nebulization on reducing the duration of mechanical ventilation during the critical initial phase of ICU treatment.	From randomization to 28 days post-randomization
Number of days without systemic antibiotics from randomization to day 28	This secondary outcome measures the number of days without systemic antibiotic use within the first 28 days after randomization. The 28-day period is chosen to assess the impact of preemptive colistin nebulization on reducing the requirement for systemic antibiotics during the initial critical period of ICU treatment	From randomization to 28 days post-randomization
ICU stay	Number of days spent in the ICU after randomization. This secondary outcome measures the length of stay in the ICU, defined as the number of days from randomization to ICU discharge. The time frame is chosen to comprehensively assess the duration of ICU treatment, which may be affected by the incidence of ventilator-associated pneumonia (VAP) and the impact of preemptive colistin nebulization on patient recovery	From randomization to ICU discharge, up to 60 days
Incidence of antibiotic-resistant bacteria	This secondary outcome measures the incidence of antibiotic-resistant bacteria isolated from routine clinical and hygiene samples collected from the date of randomization until ICU discharge. The time frame is chosen to monitor the development and prevalence of antibiotic-resistant bacteria throughout the entire ICU stay, providing insights into the impact of preemptive colistin nebulization on bacterial resistance patterns.	From randomization to ICU discharge
ICU day-28 mortality	This secondary outcome measures the mortality rate within 28 days of ICU admission. The time frame of 28 days is selected to assess early mortality outcomes related to ventilator-associated pneumonia and to evaluate the potential impact of preemptive colistin nebulization on patient survival during the initial critical period.	28 days from ICU admission

Collaborators and Investigators

• Sponsor: University Hospital Fattouma Bourguiba
• Collaborators: Agia Sofia Children's Hospital, Athens, Greece; the European Investigators Research Network for Nebulised Antibiotics in Ventilator-Associated Pneumonia; University General hospital of Larissa, University of Thessaly, Larissa, Greece; Cukurova University School of Medicine, Adana, Turquey; University general Hospital of Heraklion, University of Crete, Heraklion, Greece; Osmangazi University School of Medicine, Eskişehir, Turkey; P&A Aglaia Kyriakou Children's hospital, Athens, Greece; University General hospital Attikon, Athens, Greece; Gazi University School of Medicine, Ankara, Turquey; Cerrahpaşa University School of Medicine, Istambul, Turquey; Marmara University School of Medicine, Istambul, Turquey; Başakşehir Çam ve Sakura Hospital, Istambul, Turquey; Hôpital Mère-Enfant Abderrahim HAROUCHI University hospital ibn Rochd Casablanca, Morrocco; Hadi Cheker university hospital, sfax, Tunisia

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: June 15, 2024
• First Submitted That Met QC Criteria: June 28, 2024
• First Posted (Actual): July 5, 2024

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: pediatrics; mechanical ventilation; prevention; pneumonia; nebulization; colistin
• Additional Relevant MeSH Terms: Healthcare-Associated Pneumonia; Pathologic Processes; Disease Attributes; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Cross Infection; Iatrogenic Disease; Pathological Conditions, Signs and Symptoms; Pneumonia; Pneumonia, Ventilator-Associated; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Pharmaceutical Preparations; Lipids; Polycyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Membrane Proteins; Macrocyclic Compounds; Peptides, Cyclic; Lipopeptides; Polymyxins; Antimicrobial Cationic Peptides; Antimicrobial Peptides; Pore Forming Cytotoxic Proteins; Colistin; Saline Solution; colistinmethanesulfonic acid
• Other Study ID Numbers: FThabet

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all collected IPD
• IPD Sharing Time Frame: As soon as the manuscript is published
• IPD Sharing Access Criteria: request will be sent o the principal investigator by email, and will be shared if the reasons for request are academic or for planing similar study
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No