Nebulised Colistimethate Sodium to Prevent Pediatric Ventilator-associated Pneumonia: The COLIPED Investigation
| Registry | NCT06488794, acronym ColiPed |
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| Status | Not yet recruiting |
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| Phase | Phase 2 / Phase 3 |
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| Study type | Interventional; randomized, parallel, masking: triple, prevention |
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| Enrollment | 400 (Estimated) |
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| Sponsor | University Hospital Fattouma Bourguiba (Other); collaborators: 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, Osmangazi University School of Medicine, Eskişehir, Turkey, Aghia Sophia Children's Hospital of Athens, Athens General Children's Hospital "Pan. & Aglaia Kyriakou", Attikon Hospital, Gazi University, Cerrahpaşa University School of Medicine, Istambul, Turquey, Marmara University, Başakşehir Çam ve Sakura Hospital, Istambul, Turquey, Hôpital Mère-Enfant Abderrahim HAROUCHI University hospital ibn Rochd Casablanca, Morrocco, Hadi Cheker university hospital, sfax, Tunisia, Research Laboratory LR12SP17 |
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| Conditions | Ventilator Associated Pneumonia |
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| Interventions | colistimethate sodium, 0.9% Saline (Drug) |
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| Dates | start 2027-01-01 (estimated), primary completion 2028-12-31 (estimated), completion 2028-12-31 (estimated), first posted 2024-07-05, last updated 2026-10-08 |
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Related Papers Related Patents Related Grants Related Experts
All trials for Ventilator Associated Pneumonia All trials of colistimethate sodium All trials of 0.9% Saline
-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 5 days.
* Will be followed to check for pneumonia occurrence while they are on mechanical ventilation.
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+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 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 2 to 5 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%
+Arms and interventions
| Arm | Type | Interventions | Description |
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| colistin group | Active comparator | Drug: colistimethate sodium | 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 5 days or until extubation (whichever occurres first).
*12500 International Units of colistimethate sodium = 1 mg colistimethate sodium = 0.4 mg of colistin base. |
| Control group | Placebo comparator | Drug: 0.9% Saline | Nebulization of 6 ml of 0.9% saline twice a day for a maximum of 5 days from day 3 of invasive mechanical ventilation will be administered via a nebulizer until the nebulized solution container becomes empty. |
- colistimethate sodium (Drug), also known as Colistin: 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 5 days for eligible ventilated children starting from day 3 of mechanical ventilation.
- 0.9% Saline (Drug), also known as normal saline: Nebulization of 6 ml of 0.9% saline twice a day for a maximum of 5 days from day 3 of invasive mechanical ventilation for eligibile ventilated children
+Outcome measures
Primary outcomes
- Incidence of Ventilation Associated Pneumonia [From randomization to 28 days post-randomization]: 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
Secondary outcomes
- Incidence of Ventilation Associated Tracheobronchitis [From randomization to 28 days post-randomization]: Incidence of first episode of ventilation associated tracheobronchitis (VAT) from randomization to day 28.
- 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]: 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.
- Number of days spent on mechanical ventilation from randomization to day 28 [From randomization to 28 days post-randomization]: 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.
- Number of days without systemic antibiotics from randomization to day 28 [From randomization to 28 days post-randomization]: 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
- ICU stay [From randomization to ICU discharge, up to 60 days]: 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
- Incidence of antibiotic-resistant bacteria [From randomization to ICU discharge]: 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.
- ICU day-28 mortality [28 days from ICU admission]: 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.
+Eligibility
Sex: All, ages: 1 Month to 14 Years
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
+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. PMID 34072189
- 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
- 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
- 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