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NCT Number: NCT06819462

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.

Recruiting

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Key information

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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

Treatment and study plan

Inhaled colistin

Drug

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

Inhaled 0.9% sodium chloride

Drug

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.

Primary outcomes

  1. Prevention of early VAP

    Time frame: From randomization to 7 days

    the incidence of VAP within 7 days after randomisation

Secondary outcomes

  1. VAP incidence within 28 days

    Time frame: From randomization to 28 days

    The incidence of VAP within 28 days after randomisation

  2. Use of systemic antibiotic

    Time frame: From randomization to day 28

    The number of days of systemic antibiotic use and the daily dose of antibiotics administered within 28 days after randomization.

  3. Success of SBT

    Time frame: From randomization to first success of SBT

    The number of days from randomization to the first successful spontaneous breathing test (SBT).

  4. Invasive ventilator-free days at 28 days

    Time frame: From randomization to 28 days

    Days alive without endotracheal intubation and invasive mechanical ventilation

  5. Successful weaning from mechanical ventilation

    Time frame: From randomization to 28 days

    The proportion of patients who were successfully weaned from mechanical ventilation within 28 days after randomisation.

  6. ICU days at day 28

    Time frame: From randomization to 28 days

    The number of ICU days within 28 days after randomization

  7. Hospital days at day 28

    Time frame: From randomization to 28 days

    The number of Hospital days within 28 days after randomization

  8. 28-day mortality

    Time frame: From randomization to 28 days

    The proportion of patients who died within 28 days

  9. Incidence of AKI

    Time frame: From randomization to day 28

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Lili Huang, Doctor

CONTACT

[email protected]

+8602583262553

Sponsors and collaborators

Lead sponsor

Southeast University, China

Other

Registry information

Important dates

Study start
2025
Primary completion
2026
Study completion
2027
First posted
Feb 11, 2025
Registry last updated
Sep 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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