Different Methods of Aerosolized Polymyxin B Inhalation for Treating Carbapenem-Resistant Gram-Negative Bacterial Pneumonia.

NCT ID: NCT07086391

Last Updated: 2025-07-25

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 144 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-02-01
• Study Completion Date: 2026-02-01

Brief Summary

Study Design:

A randomized, open-label, parallel-group clinical trial comparing the efficacy and safety of jet nebulization versus vibrating mesh nebulization of sulfate polymyxin B in mechanically ventilated patients with carbapenem-resistant Gram-negative bacterial pneumonia.

Participants:

144 patients (72 per group) will be enrolled from December 2023 to December 2025.

Interventions:

Group A: 25mg polymyxin B + 5ml sterile water via jet nebulizer (respirator-assisted).

Group B: 25mg polymyxin B + 5ml sterile water via vibrating mesh nebulizer (respirator-assisted).

Both groups receive additional intravenous polymyxin B (2.0mg/kg loading dose, followed by 1.25mg/kg every 12h) starting 12h after nebulization.

Treatment duration: 14 days.

Key Procedures:

Nebulization parameters: Fixed ventilator settings (SIMV+PSV mode, tidal volume 8ml/kg, PEEP 6cmH₂O).

Bronchoalveolar lavage (BAL) and blood sampling:

BAL fluid (BALF) and blood collected pre-nebulization (baseline), 1h post-nebulization, and at steady-state (days 3-7).

BALF analyzed for polymyxin B concentration, urea nitrogen, and inflammatory mediators (IL-6, TNF-α, etc.).

Primary Outcomes:

Clinical efficacy:

Total response rate (cure + improvement). 28-day survival rate. Time to fever resolution and bacterial clearance.

Drug exposure:

Polymyxin B concentration in alveolar epithelial lining fluid (ELF) and blood.

Secondary Outcomes:

Inflammatory response: Changes in BALF and serum IL-6, TNF-α, CRP levels.

Safety:

Nephrotoxicity (changes in serum creatinine/urea nitrogen). Airway complications (bronchospasm incidence).

Assessment Timeline:

Clinical monitoring: Daily evaluation of vital signs, sputum volume, and ventilator parameters.

Lab tests: Blood tests (hematology, renal function, inflammatory markers) at baseline, days 3/7/14.

Microbiological evaluation: Sputum cultures on days 3/7/14.

Statistical Analysis:

Efficacy and safety endpoints compared between groups using t-tests or chi-square tests.

A p-value <0.05 will be considered statistically significant.

Conditions

Carbapenem-Resistant Enterobacteriaceae Infection; Pneumonia - Bacterial

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Group A: 25mg polymyxin B + 5ml sterile water via jet nebulizer (respirator-assisted).

Polymyxin B Sulfate 25mg Jet Nebulization / Vibrating Mesh Nebulization

Intervention Type: DEVICE

• Group A: 25mg polymyxin B sulfate dissolved in 5ml sterile water, administered via jet nebulizer under mechanical ventilation.
• Group B: 25mg polymyxin B sulfate dissolved in 5ml sterile water, administered via vibrating mesh nebulizer under mechanical ventilation.

Group B: 25mg polymyxin B + 5ml sterile water via vibrating mesh nebulizer (respirator-assisted).

Polymyxin B Sulfate 25mg Jet Nebulization / Vibrating Mesh Nebulization

Intervention Type: DEVICE

• Group A: 25mg polymyxin B sulfate dissolved in 5ml sterile water, administered via jet nebulizer under mechanical ventilation.
• Group B: 25mg polymyxin B sulfate dissolved in 5ml sterile water, administered via vibrating mesh nebulizer under mechanical ventilation.

Interventions

Polymyxin B Sulfate 25mg Jet Nebulization / Vibrating Mesh Nebulization

• Group A: 25mg polymyxin B sulfate dissolved in 5ml sterile water, administered via jet nebulizer under mechanical ventilation.
• Group B: 25mg polymyxin B sulfate dissolved in 5ml sterile water, administered via vibrating mesh nebulizer under mechanical ventilation.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Pneumonia diagnosed per Chinese Thoracic Society criteria (radiographic + clinical evidence).
• Sputum culture-confirmed carbapenem-resistant Gram-negative bacteria susceptible to polymyxin B.
• ≥3 days of aerosolized polymyxin B therapy.
• Mechanically ventilated with an artificial airway.

Exclusion Criteria

• Polymyxin B aerosol use planned for <3 days.
• Terminal status (life expectancy <48h).
• Severe liver/kidney dysfunction (ALT/AST >5× ULN; eGFR <30 mL/min).
• No informed consent.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fujian Medical University Union Hospital

OTHER

Sponsor Role: lead

Responsible Party

Lili Zhou

Associate Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Fujian Medical University Union Hospital

Fuzhou, Fujian, China

Site Status: RECRUITING

Countries

China

Facility Contacts

lili Zhou, MD，MS

Role: primary

zhoulili@fjmu.edu.cn

15377906840

Other Identifiers

2022YF033-03

Identifier Type: -

Identifier Source: org_study_id