Clinical trial NCT06819462: Inhaled Polymyxin E to Prevent VAP
Official title: Inhalaed Polymyxin E to Prevent Ventilator-associated Pneumonia: a Multicenter Clinical Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Ventilator-Associated Pneumonia (VAP)
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Lead sponsor: Southeast University, China
Sponsor class: OTHER
First posted: 2025-02-11
Enrollment: 434
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Age \>18 years old
2. Patients with brain injury admitted to ICU (including brain injury caused by trauma, cerebral hemorrhage, cerebral infarction, and cardiac arrest)
3. GCS score\<12 points
4. Mechanical ventilation time ≥ 48 hours
5. Sign informed consent

Exclusion Criteria:

1. Existing lung diseases that require long-term inhaled medication treatment.
2. Lower respiratory tract infection at admission.
3. New or persistent infiltration on chest imaging within 48 hours after admission.
4. Expected removal of endotracheal tube within the next 24 hours.
5. Mechanical ventilation time before enrollment exceeds 96 hours.
6. Tracheostomy patients.
7. Current or recent use of polymyxin E (within 24 hours).
8. Allergy to polymyxin E.
9. Allergic pregnant or lactating women.
10. Severe neuromuscular lesions.
11. Severe other organ dysfunction. Expected short-term death (48 hours) or palliative treatment.
12. Late stage solid organ or blood system tumors. Expected survival\<30 days. 13. Participate in other clinical studies within 30 days

Primary outcomes:
measure: Prevention of VAP
timeFrame: From randomization to 7 days
Secondary outcomes:
measure: VAP incidence within 28 days
timeFrame: From randomization to 28 days
measure: Changes of CPIS within day 28
timeFrame: from randomization to extubation or day 28, whichever occurs first
measure: Use of systemic antibiotic
timeFrame: From randomization to day 28
measure: Success of SBT
timeFrame: From randomization to first success of SBT
measure: Invasive ventilator-free days at 28 days
timeFrame: From randomization to 28 days
measure: Successful of weaning from ventilator
timeFrame: From randomization to 28 days
measure: ICU days at day 28
timeFrame: From randomization to 28 days
measure: Hospital days at day 28
timeFrame: From randomization to 28 days
measure: 28-day mortality
timeFrame: From randomization to 28 days
measure: Incidence of AKI
timeFrame: From randomization to day 28
Other outcomes:
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