Antimicrobial Treatment in Patients With Ventilator-associated Tracheobronchitis: a Prospective Randomized Placebo-controlled Double-blind Multicenter Trial
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 103
- 试验地点
- 1
- 主要终点
- The percentage of patients with a transition from VAT to VAP,
研究概览
简要总结
Antimicrobial treatment could be beneficial in patients with ventilator-associated tracheobronchitis (VAT). The hypothesis of this study is that antibiotic treatment for VAT (3 or 7 days), compared with no antibiotic treatment, would reduce the incidence of transition from VAT to ventilator-associated pneumonia (VAP).
详细描述
The main objective of this randomized controlled multicenter double-blind trial is to assess the efficiency of two durations (3 or 7 days) of antibiotic treatment for VAT, compared with no antibiotic treatment, in reducing the incidence of transition from VAT to ventilator-associated pneumonia (VAP).
Secondary objectives are to determine the impact of two durations (3 or 7 days) of antibiotic treatment for VAT, compared with no antibiotic treatment, on:
- duration of mechanical-ventilation free days
- duration of antibiotic free days
- length of ICU stay
- mortality at day 28 and day 90
- incidence of ICU-acquired colonization related to multidrug resistant (MDR) bacteria
- incidence of ICU-acquired infection related to MDR bacteria
- incidence of ventilator-associated events After informed consent, patients will be randomized (1:1:1) to receive 0 (control group), 3 or 7 days (experimental groups) of antibiotic treatment for VAT
Antibiotic treatment is standardized, based on the time of onset of VAT, and presence of risk factors for MDR bacteria:
- patients with early-onset VAT with no risk factor for MDR bacteria will receive ceftriaxone (2 g iv every 24h).
- patients with late-onset VAT (after day 4 of mechanical ventilation), or with at least one risk factor for MDR bacteria will receive imipenem (1 g iv every 8h), and ciprofloxacin (400 mg iv every 8h) as empirical treatment. When methicillin-resistant Staphylococcus aureus is suspected, linezolid (600 mg iv every 12h) will be added to empirical treatment.
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
- Triple (Participant, Care Provider, 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
- •All adult patients hospitalized in the ICU with a first episode of VAT diagnosed >48 hours after starting invasive mechanical ventilation are eligible for this study.
- •VAT is defined using the following criteria:
- •absence of new infiltrate on chest X ray
- •two of the three following conditions: fever > 38.5 °C or <36.5, leucocyte count > than 12 000 cells per μL or <than 4000 cells per μL purulent tracheal secretions
- •and positive tracheal aspirate (≥105 cfu/mL)
排除标准
- •long-term tracheostomy at ICU admission
- •patients who develop VAP before VAT
- •patients already receiving antibiotics active against all the microorganisms responsible for VAT
- •severe immunosuppression
- •pregnancy or breastfeeding
- •patients <18 years
- •patients already included in another study, with potential interaction with the primary objective of the current study
- •known resistance to imipenem and ciprofloxacin of bacteria responsible for VAT
- •treatment limitation decisions
- •moribund patients (likely to die within 24 h)
- •allergy to any of study drugs: hypersensitivity to any carbapenem, severe hypersensitivity (for example anaphylactic reaction or severe cutaneous reaction) to any other antibiotic form beta-lactam group (such as penicillin or cephalosporin), severe hypersensitivity (for example anaphylactic reaction) to any other antibiotic from beta-lactam group (penicillin, monobactam or carbapenem), hypersensitivity to quinolones
研究组 & 干预措施
no antibiotic treatment for VAT
3 days of placebo
干预措施: placebo (Drug)
antibiotic treatment for 3 days
Patients randomized in one of the two experimental groups will receive 3 days of antimicrobials. Antibiotic treatment is standardized, based on the time of onset of VAT, and presence of risk factors for MDR bacteria:
- patients with early-onset VAT (< 5 days of mechanical ventilation), with no risk factor for MDR will receive ceftriaxone .
- patients with late-onset VAT (≥5 days of mechanical ventilation), or with at least one risk factor for multidrug resistant bacteria will receive imipenem , and ciprofloxacin as empirical treatment.
When methicillin-resistant Staphylococcus aureus (MRSA) is suspected linezolid will be added to empirical treatment.
3 days of imipenem and ciprofloxacin with optional linezolid, followed by 4 d of placebo
干预措施: ceftriaxone (Drug)
antibiotic treatment for 3 days
Patients randomized in one of the two experimental groups will receive 3 days of antimicrobials. Antibiotic treatment is standardized, based on the time of onset of VAT, and presence of risk factors for MDR bacteria:
- patients with early-onset VAT (< 5 days of mechanical ventilation), with no risk factor for MDR will receive ceftriaxone .
- patients with late-onset VAT (≥5 days of mechanical ventilation), or with at least one risk factor for multidrug resistant bacteria will receive imipenem , and ciprofloxacin as empirical treatment.
When methicillin-resistant Staphylococcus aureus (MRSA) is suspected linezolid will be added to empirical treatment.
3 days of imipenem and ciprofloxacin with optional linezolid, followed by 4 d of placebo
干预措施: ciprofloxacin (Drug)
antibiotic treatment for 3 days
Patients randomized in one of the two experimental groups will receive 3 days of antimicrobials. Antibiotic treatment is standardized, based on the time of onset of VAT, and presence of risk factors for MDR bacteria:
- patients with early-onset VAT (< 5 days of mechanical ventilation), with no risk factor for MDR will receive ceftriaxone .
- patients with late-onset VAT (≥5 days of mechanical ventilation), or with at least one risk factor for multidrug resistant bacteria will receive imipenem , and ciprofloxacin as empirical treatment.
When methicillin-resistant Staphylococcus aureus (MRSA) is suspected linezolid will be added to empirical treatment.
3 days of imipenem and ciprofloxacin with optional linezolid, followed by 4 d of placebo
干预措施: imipenem (Drug)
antibiotic treatment for 3 days
Patients randomized in one of the two experimental groups will receive 3 days of antimicrobials. Antibiotic treatment is standardized, based on the time of onset of VAT, and presence of risk factors for MDR bacteria:
- patients with early-onset VAT (< 5 days of mechanical ventilation), with no risk factor for MDR will receive ceftriaxone .
- patients with late-onset VAT (≥5 days of mechanical ventilation), or with at least one risk factor for multidrug resistant bacteria will receive imipenem , and ciprofloxacin as empirical treatment.
When methicillin-resistant Staphylococcus aureus (MRSA) is suspected linezolid will be added to empirical treatment.
3 days of imipenem and ciprofloxacin with optional linezolid, followed by 4 d of placebo
干预措施: linezolid (Drug)
antibiotic treatment for 3 days
Patients randomized in one of the two experimental groups will receive 3 days of antimicrobials. Antibiotic treatment is standardized, based on the time of onset of VAT, and presence of risk factors for MDR bacteria:
- patients with early-onset VAT (< 5 days of mechanical ventilation), with no risk factor for MDR will receive ceftriaxone .
- patients with late-onset VAT (≥5 days of mechanical ventilation), or with at least one risk factor for multidrug resistant bacteria will receive imipenem , and ciprofloxacin as empirical treatment.
When methicillin-resistant Staphylococcus aureus (MRSA) is suspected linezolid will be added to empirical treatment.
3 days of imipenem and ciprofloxacin with optional linezolid, followed by 4 d of placebo
干预措施: placebo (Drug)
结局指标
主要结局
The percentage of patients with a transition from VAT to VAP,
时间窗: from randomization to day 28 (4 weeks)
VAP is defined using the following criteria: 1. new or progressive pulmonary infiltrate 2. two of the following criteria: temperature \>38°C or \<36.5°C leukocyte count \>12,000/μL or \<4,000/μL purulent endotracheal aspirate 3. positive tracheal aspirate (≥105 cfu/mL) or bronchoalveolar lavage (≥104 cfu/mL). VAP will be considered as subsequent to VAT, when it is diagnosed \>24h after VAT occurrence. Only first episodes of VAP diagnosed \>48h after starting mechanical ventilation will be taken into account.
次要结局
- percentage of patients with ICU-acquired colonization related to MDR bacteria(from randomization to day 28 (4 weeks))
- duration of mechanical ventilation-free days(from randomization to day 28 (4 weeks))
- duration of antibiotic free-days(from randomization to day 28 (4 weeks))
- length of ICU stay(from randomization to day 28 (4 weeks))
- mortality(at day 28 and day 90 after randomization)
- percentage of patients with ventilator-associated events(from randomization to day 28 (4 weeks))
- percentage of patients with ICU-acquired infection related to MDR bacteria(from randomization to day 28 (4 weeks))