Inhaled Polymyxin E to Prevent VAP

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

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: Not yet recruiting
• Conditions: Ventilator-Associated Pneumonia (VAP); Inha'le'd
• Intervention / Treatment: Drug: Inhaled Placebo; Drug: inhaled corticosteroids and other asthma drugs

• Study Type: Interventional
• Enrollment (Estimated): 434
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

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

Description

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

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
Placebo Comparator: NS Group; The patients began to nebulize the drugs within 24 hours after screening. Both groups inhaled twice a day for 3 days. The NS group inhaled with normal saline .	Drug: Inhaled Placebo; 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 .
Experimental: Polymyxin E Group; The patients began to inhaled the drugs within 24 hours after screening. Both groups inhaled twice a day for 3 days. The Polymyxin E Group inhaled polymyxin E 75 mg bid .	Drug: inhaled corticosteroids and other asthma drugs; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevention of VAP	The incidence of VAP from randomization to day 7.	From randomization to 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day mortality	The proportion of patients who are died within 28 days	From randomization to 28 days
Invasive ventilator-free days at 28 days	Days alive without endotracheal intubation and invasive mechanical ventilation	From randomization to 28 days
VAP incidence within 28 days	Incidence of VAP from randomization to day 28	From randomization to 28 days
Changes of CPIS within day 28	Changes of clinical pulmonary infection scores after randomization（CPIS）	from randomization to extubation or day 28, whichever occurs first
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
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 of weaning from ventilator	The proportion of patients who Successfully weaned from mechanical ventilator within 28 days.	From randomization to 28 days
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
Incidence of AKI	The proportion of patients who were newly diagnosed AKI within 28 days after randomization	From randomization to day 28

Collaborators and Investigators

• Sponsor: Southeast University, China

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: February 5, 2025
• First Submitted That Met QC Criteria: February 5, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 5, 2025
• Last Verified: February 1, 2025

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; Cross Infection; Iatrogenic Disease; Pneumonia; Pneumonia, Ventilator-Associated
• Other Study ID Numbers: 2025VAP

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