Nebulised Colistimethate Sodium to Prevent Pediatric Ventilator-associated Pneumonia

NCT06488794 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: FThabet
• Study Type: interventional
• Target: 400
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Ventilator Associated Pneumonia

Keywords

colistin; mechanical ventilation; pneumonia; nebulization; prevention; pediatrics

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Incidence of Ventilation Associated Tracheobronchitis

  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

  From randomization to 28 days post-randomization

• Number of days spent on mechanical ventilation from randomization to day 28

  From randomization to 28 days post-randomization

• Number of days without systemic antibiotics from randomization to day 28

  From randomization to 28 days post-randomization

• ICU stay

  From randomization to ICU discharge, up to 60 days

Study Arms (2)

colistin group

ACTIVE COMPARATOR

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

Control group

PLACEBO COMPARATOR

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

Interventions

colistimethate sodium DRUG

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.

Also known as: Colistin

colistin group

0.9% Saline DRUG

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

Also known as: normal saline

Control group

Eligibility Criteria

• Age: 1 Month - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Related Publications (4)

• 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.

  PMID: 34072189 BACKGROUND

• 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.

  PMID: 28458172 BACKGROUND

• 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.

  PMID: 26405294 BACKGROUND

• 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.

  PMID: 28942198 BACKGROUND

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated; Pneumonia

Interventions

colistinmethanesulfonic acid; Colistin; Saline Solution

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Polymyxins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Antimicrobial Cationic Peptides; Peptides; Amino Acids, Peptides, and Proteins; Antimicrobial Peptides; Pore Forming Cytotoxic Proteins; Membrane Proteins; Proteins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Central Study Contacts

Farah C Thabet, MD

CONTACT

0021629742011; thabetfarah@yahoo.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PROFESSOR IN PEDIATRICS

Study Record Dates

• First Submitted: June 15, 2024
• First Posted: July 5, 2024
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: As soon as the manuscript is published
• 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