Inhaled Colistin to Prevent Ventilator-Associated Pneumonia in Patients With Acute Brain Injury

Ventilator associated pneumonia is the most common manifestation of hospital acquired infections in ICU. The incidence of ventilator-associated pneumonia in patients receiving mechanical ventilation is as high as 20% -71%, which can lead to increased systemic antibiotic use, prolonged mechanical ventilation time and ICU stay, and increased treatment costs. In addition, ventilator-associated pneumonia is also the main cause of hospital infection related deaths in critically ill patients.

However, there is a certain buffer time for patients to develop ventilator-associated pneumonia after receiving endotracheal intubation. Previous studies have found that the peak incidence occurs after 7 days of mechanical ventilation, so there is an opportunity for early treatment to prevent infection. Despite the implementation of numerous preventive measures for ventilator-associated pneumonia over the decades, such as reducing sedation and withdrawal protocols, patient positioning, oral care, prophylactic probiotics, prophylactic antibiotics, and the use of silver plated endotracheal tubes. Among them, the research on the preventive use of antibiotics has a history of over 30 years and is a topic of substantial debate. Prophylactic use of antibiotics includes systemic application and local nebulization inhalation, and inhaled antibiotics may be an effective measure for preventing ventilator-associated pneumonia. Potential extensively drug-resistant Gram negative (XDR-GN) bacteria, such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, are common pathogens causing VAP in ICU. The mortality rate of VAP caused by XDR-GN pathogen may be higher than 70%. With the increasing incidence of multidrug-resistant microorganisms, nebulized or inhaled aminoglycoside antibiotics are often used as empirical or definitive treatment for VAP in ICU patients. The previous group of antibiotics, polymyxin, has returned to the view of medical staff. Sodium polymyxin E methanesulfonate has been used as a salvage therapy for XDR-GN bacteria causing pneumonia, demonstrating its activity against XDR-GN causing VAP in critically ill patients. The guidelines of the Infectious Diseases Society of America (IDSA) on hospital acquired pneumonia also indicate that patients with Gram negative pneumonia caused by drug-resistant bacteria are sensitive to polymyxins. In this randomized controlled study, we aim to investigate the effect of prophylactic use of polymyxin E nebulized inhalation on the incidence of VAP.

Study Overview

• Status: Recruiting
• Conditions: Ventilator-Associated Pneumonia (VAP); Inha'le'd
• Intervention / Treatment: Drug: Inhaled colistin; Drug: Inhaled 0.9% sodium chloride

• Study Type: Interventional
• Enrollment (Estimated): 444
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lili Huang, Doctor; Phone Number: +8602583262553; Email: caowangyou007@126.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
      • Contact: Lili Huang, Doctor; Phone Number: +8602583262553; Email: caowangyou007@126.com
      • Contact: Hui Chen, Doctor; Phone Number: +8602583262553; Email: zdywc2012@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients aged more than or equal to 18 years and less than 80 years
2. ABI patients admitted to the ICU, including TBI, intracranial haemorrhage, ischaemic stroke, post-cardiac arrest hypoxic-ischaemic encephalopathy or other acute neurological insults
3. Glasgow Coma Scale (GCS) score ≤12
4. Duration of mechanical ventilation more than or equal to 48 hours at enrolment
5. Written informed consent provided by the participant's legally authorised representative.

Exclusion Criteria:

1. patients with suspected or confirmed VAP on the day of enrolment
2. Anticipated extubation within the next 24 hours.
3. Duration of mechanical ventilation exceeding 96 hours prior to enrolment.
4. Patients currently receiving or having recently received (within the preceding 24 hours) polymyxin (administered intravenously and/or via nebulization).
5. Known hypersensitivity to polymyxin.
6. Pregnant or breastfeeding women.
7. Myasthenia gravis.
8. Patient with high risk of death within the first 48h after ICU admission.
9. Advanced-stage solid organ malignancy or hematological malignancy.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Colistin Group; Nebulization was initiated within 24 hours after patient enrollment. Experimental group received nebulization with colistin (75 mg per dose） twice daily for 3 consecutive days with a vibrating mesh nebulizer.	Drug: Inhaled colistin; Colistin powder will be solubilised in 0.9% Nacl (75mg per 5 mL)， and used for nebulisation twice a day at a dose of 75mg for 3 days
Placebo Comparator: Control Group; Nebulization was initiated within 24 hours after patient enrollment. Control group received nebulization with an equivalent volume of 0.9% sodium chloride twice daily for 3 consecutive days with a vibrating mesh nebulizer.	Drug: Inhaled 0.9% sodium chloride; Saline solution of 0.9% sodium chloride (NaCl) will be used as placebo. The equivalent volume of 0.9% NaCl will be placed in the nebuliser and delivered twice a day for 3 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevention of early VAP	the incidence of VAP within 7 days after randomisation	From randomization to 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Invasive ventilator-free days at 28 days	Days alive without endotracheal intubation and invasive mechanical ventilation	From randomization to 28 days
Use of systemic antibiotic	The number of days of systemic antibiotic use and the daily dose of antibiotics administered within 28 days after randomization.	From randomization to day 28
ICU days at day 28	The number of ICU days within 28 days after randomization	From randomization to 28 days
Hospital days at day 28	The number of Hospital days within 28 days after randomization	From randomization to 28 days
VAP incidence within 28 days	The incidence of VAP within 28 days after randomisation	From randomization to 28 days
Success of SBT	The number of days from randomization to the first successful spontaneous breathing test (SBT).	From randomization to first success of SBT
Successful weaning from mechanical ventilation	The proportion of patients who were successfully weaned from mechanical ventilation within 28 days after randomisation.	From randomization to 28 days
28-day mortality	The proportion of patients who died within 28 days	From randomization to 28 days
Incidence of AKI	The proportion of patients who were newly diagnosed acute kidney injury (AKI) within 28 days after randomization, defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria.	From randomization to day 28

Collaborators and Investigators

• Sponsor: Southeast University, China

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: February 5, 2025
• First Submitted That Met QC Criteria: February 5, 2025
• First Posted (Actual): February 11, 2025

Study Record Updates

• Last Update Posted (Actual): September 4, 2026
• Last Update Submitted That Met QC Criteria: September 1, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Healthcare-Associated Pneumonia; Pathologic Processes; Disease Attributes; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Cross Infection; Iatrogenic Disease; Pathological Conditions, Signs and Symptoms; Pneumonia, Ventilator-Associated; Circulatory and Respiratory Physiological Phenomena; Inorganic Chemicals; Chlorine Compounds; Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Sodium Compounds; Chlorides; Hydrochloric Acid; Inhalation; Sodium Chloride
• Other Study ID Numbers: PREABI-VAP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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