A Prospective Clinical Study on Different Methods of Aerosolized Polymyxin B Inhalation for the Treatment of Carbapenem-Resistant Gram-Negative Bacterial Pneumonia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 144
- 试验地点
- 1
- 主要终点
- Clinical efficacy
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Clinical efficacy
时间窗: Baseline (pre-treatment); End of Treatment (EOT, 14 days after starting polymyxin B)
Percentage of patients with cure or improvement based on symptom resolution, microbiological clearance, and radiographic findings.
次要结局
- 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))
研究者
Lili Zhou
Associate Chief Physician
Fujian Medical University Union Hospital