Ventilator Associated Pneumonia: Addition of Tobramycin Inhalation Antibiotic Treatment to Standard IV Antibiotic Treatment
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- response after 72 h of treatment
研究概览
简要总结
This study evaluates the addition of tobramycin inhalation treatment to standard intravenous therapy in the treatment of ventilator associated pneumonia.
详细描述
Rationale: Approximately 9-27% of mechanically ventilated patients in the intensive care unit (ICU) develop ventilator-associated pneumonia (VAP). Patients in whom VAP develops have a higher mortality rate up to 50%, stay longer in the intensive care unit (ICU), and require more resources than those without the disease. Despite the availability of modern ICU care and modern antibiotics, the overall clinical cure rate after 72 hours of antibiotic treatment for VAP is only 40%. The cure rate for Pseudomonas aeruginosa is even lower. It is unclear why VAP cure rates are so low. The ATS guidelines recommend IV antibiotic treatment (IV AB), especially directed against gram-negative microorganisms. However, the relatively poor response rates seen with intravenous therapy of VAP and the emergence of MDR organisms makes new treatment options desirable. The ATS/IDSA VAP guidelines recommend that "adjunctive therapy with an inhaled aminoglycoside or polymyxin (colistin) for MDR Gram-negative pneumonia should be considered, especially in patients who are not improving". It is therefore necessary to investigate whether adjunctive therapy with inhalation Tobramycin could ameliorate prognosis. The recommendations by the Society of Infectious Diseases Pharmacists are similar.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Mechanical ventilation 48 hours or more
- •New or progressive radiologic pulmonary infiltrate
- •Together with at least two of the following three criteria (< 24 h):
- •temperature >38°C
- •leukocytosis >12,000/mm3 or leucopenia <4,000/mm3
- •purulent respiratory secretions
排除标准
- •patients with allergy to tobramycin
- •pregnancy
- •expected to die within 72 hours after enrollment
研究组 & 干预措施
tobramycin inhalation
twice daily tobramycin inhalation (Bramitob) 300 mg and standard intravenous antibiotics treatment
干预措施: tobramycin inhalation (Drug)
Placebo
twice daily placebo inhalation and standard intravenous antibiotics treatment
干预措施: placebo (Drug)
结局指标
主要结局
response after 72 h of treatment
时间窗: 72 hours
non response is considered when at least one of the following is present 1. No improvement of the arterial O2 tension to inspired O2 fraction ratio 2. Persistence of fever (≥38°C) or hypothermia (\<35.5°C) together with purulent respiratory secretions 3. increase in the pulmonary infiltrates on chest radiograph of greater than or equal to 50% 4. occurrence of septic shock or multiple organ dysfunction syndrome, defined as three or more organ system failures not present on Day 1
次要结局
- Mortality rate(day 90)
- ICU survival(day 90)
- Ventilator free days at day 28(up to 28 days)
- Day of normalisation of CRP(day 90)
- APACHE II score(discharge ICU, expected average time of discharge is 10 days)
- Sequential Organ Failure Assessment score (SOFA)(discharge ICU, expected average time of discharge is 10 days)
- Lung Injury Score (LIS)(discharge ICU, expected average time of discharge is 10 days)
- Day of normalisation of chest X-ray(day 90)
- Discharge from the ICU(up to 60 days)
- Absence of hospital admittance at day 60(day 60)
- Adverse events(day 90)
- Day of normalisation of procalcitonin (PCT)(day 90)
- Eradication of pathogens(day 90)
- Clinical Pulmonary Infectious Score (CPIS)(discharge ICU, expected average time of discharge is 10 days)
- Multiple Organ Dysfunction score (MODS)(discharge ICU, expected average time of discharge is 10 days)
研究者
R.A.S. Hoek, MD
MD
Erasmus Medical Center