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

NCT07086391 | Recruiting

• 1 other identifier: 2022YF033-03
• Study Type: observational
• Target: 144
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Clinical efficacy

  Percentage of patients with cure or improvement based on symptom resolution, microbiological clearance, and radiographic findings.

  Baseline (pre-treatment); End of Treatment (EOT, 14 days after starting polymyxin B)

Secondary Outcomes (2)

• 28-Day Survival Rate

  Baseline (pre-treatment); End of Treatment (EOT, 28 days after starting polymyxin B)

• Microbiological Clearance Rate

  Baseline (pre-treatment); End of Treatment (EOT, 14 days after starting polymyxin B)

Study Arms (2)

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

Device: Polymyxin B Sulfate 25mg Jet Nebulization / Vibrating Mesh Nebulization

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

Device: Polymyxin B Sulfate 25mg Jet Nebulization / Vibrating Mesh Nebulization

Interventions

Polymyxin B Sulfate 25mg Jet Nebulization / Vibrating Mesh Nebulization 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 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).

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Mechanically ventilated adults with carbapenem-resistant Gram-negative bacterial pneumonia (e.g., Pseudomonas aeruginosa) confirmed by sputum culture and susceptible to polymyxin B. Participants must receive ≥3 days of aerosolized polymyxin B via endotracheal tube/tracheostomy. Exclusions: life expectancy \<48h, severe liver/kidney dysfunction, or lack of informed consent.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fujian Medical University Union Hospital: lead

Study Sites (1)

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

RECRUITING

MeSH Terms

Conditions

Pneumonia, Bacterial

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 28 Days
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Chief Physician

Study Record Dates

• First Submitted: April 14, 2025
• First Posted: July 25, 2025
• Study Start: February 1, 2023
• Primary Completion: July 1, 2025
• Study Completion: February 1, 2026
• Last Updated: July 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)