Impact of the Duration of Antibiotics on Clinical Events in Patients With Pseudomonas Aeruginosa Ventilator-associated Pneumonia : a Randomized Controlled Study (iDIAPASON)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 190
- 试验地点
- 1
- 主要终点
- A composite endpoint of morbi-mortality combining Day-90 mortality and PA-VAP recurrence rate during hospitalization in the ICU (within 90 days).
研究概览
简要总结
Ventilator-associated pneumonia (VAP) accounts for 25% of infections in intensive care units (Réseau RAISIN 2012). A short duration (8 days; SD) vs. long duration (15 days; LD) of antibiotic therapy has a comparable clinical efficacy with less antibiotic use and less multidrug-resistant pathogens (MDR) emergence. These results have led the American Thoracic Society to recommend SD therapy for VAP, with the exception of documented VAP of non-fermenting Gram negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA-VAP), due to the absence of studies focusing specifically on PA-VAP. Thus the beneficial effect of SD therapy in PA-VAP is still a matter of debate. In a small (n=127) subgroup analysis, a higher rate of recurrence with SD therapy (n=21, 32.8%) has been observed compared with LD therapy group (n=12, 19.0%). Unfortunately, the definition of recurrence was essentially based on microbiological rather than clinical data, and the higher rate of recurrence observed could rather reflect a higher rate of colonization more than a new infection.
Interestingly, a trend for a lower rate of mortality was also observed in the SD group (n=15, 23.4%) compared with the LD group (n=19, 30.2%), but this study was clearly underpowered to detect a difference of mortality between groups.
The two strategies were considered as not different, for the risk of mortality in a recent meta-analysis, performed on the very few available studies (n=2), that (OR = 1.33, 95% CI [0.33 to 5.26] for SD vs. LD strategies respectively). However, this conclusion remains questionable considering the large confidence interval of the risk and the power of these studies.
Primary objective and assessment criterion: To assess the non-inferiority of a short duration of antibiotics (8 days) vs. prolonged antibiotic therapy (15 days) in P. aeruginosa ventilator-associated pneumonia (PA-VAP) on a composite end-point combining Day-90 mortality and PA-VAP recurrence rate during hospitalization in the ICU.
Study Design :
Randomized, open-labeled non inferiority controlled trial 32 French Intensive Care Units participating to the study
Research period:
Total study duration: 27 months Inclusion period: 24 months Duration of participation for a patient: 90 days
详细描述
Ventilator-associated pneumonia (VAP) is a major cause of morbidity and mortality in the ICU, accounting for 25% of infections in intensive care units (Réseau RAISIN 2012). From 1975 to 2003, the incidence of hospital-acquired pneumonia caused by Pseudomonas aeruginosa (PA) has almost doubled, from 9.6% to 18.1%. In a US national large-scale survey, PA was the most frequently isolated gram-negative aerobic bacterium from ICUs (23%) and also the most frequent bacterium isolated from the respiratory tract (31.6%).
PA-VAP is associated with a high mortality ranging from 40% up to 69%, and with high rates of recurrence despite adequate antimicrobial therapy. In a large randomized trial regarding the optimal duration of antibiotic therapy in overall VAPs, the rate of recurrence among the subgroup of non-fermenting Gram negative bacilli (NF-GNB) documented VAP varied between 19.0% and 32.8%, according to the randomization arm. Finally, a recently published cohort about 393 PA-VAP in 314 patients, the composite criteria failure treatment (death and recurrence) occured in 112 cases (28.5%).
Hypothesis A short duration antibiotherapy (8 days) vs. long duration antibiotherapy (15 days) in treatment of Pseudomonas aeruginosa Ventilator-Associated Pneumonia (PA-VAP) is safe and not associated with an increased mortality or recurrence rate of PA-VAP.
The demonstration of this hypothesis could lead to decrease antibiotic exposure during the hospitalization in the Intensive Care Unit (ICU) and in turn reduce the acquisition and the spread of multidrug-resistant pathogens (MDR).
Objectives
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
- None
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
- •Patients older than 18 years
- •Mechanical ventilation ≥ 48 hours
- •Documented Pseudomonas aeruginosa ventilator-associated pneumonia:
- •Clinical suspicion (≥ two criteria including: fever> 38.5°C,leukocytosis > 10 Giga/L or leukopenia < 4 Giga/L, purulent tracheobronchial secretions and a new or persistent infiltrate on chest radiography).
- •Documented Pseudomonas aeruginosa positive quantitative culture of a respiratory sample: bronchoalveolar lavage fluid (significant threshold, >104cfu/ml) or plugged telescopic catheter (significant threshold, >103cfu/ml) or quantitative endotracheal aspirate (significant threshold, >106cfu/ml).
- •Written informed consent
- •Patient affiliated to French social security
排除标准
- •Immunocompromised patients (HIV, immunosuppressive therapy, corticosteroids> 0.5 mg / kg per day for more than a month)
- •Patients receiving antibiotic therapy for extrapulmonary infection
- •Patients in whom a procedure of withdrawing life-sustaining treatment has been established
- •Pregnancy
- •Patients included in another interventional study
- •Chronic pulmonary colonization with Pseudomonas aeruginosa: patients with Chronic Obstructive Pulmonary Disease (COPD) or bronchiectasis, with a positive respiratory sample at infra threshold rate for Pseudomonas aeruginosa (ie<103 CFUs/mL for protected specimen brush or <106 CFUs/mL for tracheal aspirate), obtained in the absence of pneumonia or exacerbation during the 6 months before the ICU admission.
- •Patient under guardianship or curatorship
研究组 & 干预措施
8 days of effective antibiotic treatment
Antibiotic treatment should be started just after realization of bacteriological sampling, and then converted into a narrow-spectrum therapy, based on culture results, for a total duration of effective antibiotic therapy against PA of 8 days.
干预措施: 8 days of effective antibiotic treatment (Drug)
15 days of effective antibiotic treatment
Antibiotic treatment should be started just after realization of bacteriological sampling, and then converted into a narrow-spectrum therapy, based on culture results, for a total duration of effective antibiotic therapy against PA of 15 days.
干预措施: 15 days of effective antibiotic treatment (Drug)
结局指标
主要结局
A composite endpoint of morbi-mortality combining Day-90 mortality and PA-VAP recurrence rate during hospitalization in the ICU (within 90 days).
时间窗: 90 days after effective antibiotherapy
A composite endpoint combining Day-90 mortality and PA-VAP recurrence rate during hospitalization in the ICU (within 90 days). Recurrence will be defined a posteriori by 3 independent experts with predefined criteria: clinical suspicion of VAP (≥ two criteria including: fever\> 38.5 ° C, leukocytosis \> 10 Giga/L or leukopenia \< 4 Giga/L, purulent tracheobronchial secretions and a new or persistent infiltrate on chest radiography) associated with a positive quantitative culture of a respiratory sample (bronchoalveolar lavage fluid (significant threshold ≥104 colony-forming units/mL) or plugged telescopic catheter (significant threshold ≥103 colony-forming units/mL) or quantitative endotracheal aspirate distal pulmonary secretion samples (significant threshold ≥106 colony-forming units/mL)).
次要结局
- Exposure to antibiotics during the hospitalization in the ICU (days)(during stay in the ICU : up to 90 days)
- Measure of morbidity in ICU by duration of mechanical ventilation (days)(Day 30 and Day 90 after effective antibiotherapy)
- Measure of morbidity in ICU by duration of hospitalization in ICU (days)(Day 30 and Day 90 after effective antibiotherapy)
- Measure of mortality rate (%) in the ICU(Day 30 and Day 90 after effective antibiotherapy)
- Acquisition of MDR during the hospitalization in the ICU.(during stay in the ICU : up to 90 days)
- Number of extrapulmonary infections during the hospitalization in the ICU(during stay in the ICU : up to 90 days)
- Type of extrapulmonary infections during the hospitalization in the ICU(during stay in the ICU : up to 90 days)