Inhaled Polymyxin E to Prevent VAP

NCT06819462 | Not Yet Recruiting DMC

• 1 other identifier: 2025VAP
• Study Type: interventional
• Target: 434
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Ventilator-Associated Pneumonia (VAP); Inha'le'd

Outcome Measures

Primary Outcomes (1)

• Prevention of VAP

  The incidence of VAP from randomization to day 7.

  From randomization to 7 days

Secondary Outcomes (10)

• VAP incidence within 28 days

  From randomization to 28 days

• Changes of CPIS within day 28

  from randomization to extubation or day 28, whichever occurs first

• Use of systemic antibiotic

  From randomization to day 28

• Success of SBT

  From randomization to first success of SBT

• Invasive ventilator-free days at 28 days

  From randomization to 28 days

Study Arms (2)

NS Group

PLACEBO COMPARATOR

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

Polymyxin E Group

EXPERIMENTAL

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

Interventions

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 .

NS Group

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.

Also known as: Inhaled

Polymyxin E Group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Southeast University, China: lead

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated

Interventions

Inhalation

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: doctor

Study Record Dates

• First Submitted: February 5, 2025
• First Posted: February 11, 2025
• Study Start: February 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: February 11, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share