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NCT Number: NCT06819462

Inhaled Polymyxin E to Prevent VAP

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.

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Key information

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

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

Exclusion criteria

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

Treatment and study plan

Inhaled placebo

Drug

Inhalation of drugs was started within 24 hours after the screening of patients. Both groups inhaled with vibrating mesh spray twice a day for 3 days. The NS group inhaled with normal saline .

inhaled corticosteroids and other asthma drugs

Drug

Inhalation of drugs was started within 24 hours after the screening of patients. Both groups used vibrating mesh spray twice a day for 3 days. The Polymyxin E group inhaled polymyxin, 75 mg bid.

Other names: Inhaled

Primary outcomes

  1. Prevention of VAP

    Time frame: From randomization to 7 days

    The incidence of VAP from randomization to day 7.

Secondary outcomes

  1. VAP incidence within 28 days

    Time frame: From randomization to 28 days

    Incidence of VAP from randomization to day 28

  2. Changes of CPIS within day 28

    Time frame: from randomization to extubation or day 28, whichever occurs first

    Changes of clinical pulmonary infection scores after randomization(CPIS)

  3. 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.

  4. 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)

  5. Invasive ventilator-free days at 28 days

    Time frame: From randomization to 28 days

    Days alive without endotracheal intubation and invasive mechanical ventilation

  6. Successful of weaning from ventilator

    Time frame: From randomization to 28 days

    The proportion of patients who Successfully weaned from mechanical ventilator within 28 days.

  7. ICU days at day 28

    Time frame: From randomization to 28 days

    The number of ICU days within 28 days after randomization

  8. Hospital days at day 28

    Time frame: From randomization to 28 days

    The number of Hospital days within 28 days after randomization

  9. 28-day mortality

    Time frame: From randomization to 28 days

    The proportion of patients who are died within 28 days

  10. Incidence of AKI

    Time frame: From randomization to day 28

    The proportion of patients who were newly diagnosed AKI within 28 days after randomization

Sponsors and collaborators

Lead sponsor

Southeast University, China

Other

Registry information

Official study title

Inhalaed Polymyxin E to Prevent Ventilator-associated Pneumonia: a Multicenter Clinical Study

Important dates

Study start
2025
Primary completion
2027
Study completion
2028
First posted
Feb 11, 2025
Registry last updated
Feb 11, 2025

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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