BetaLACTA® Test-guided Early De-escalation of Empirical Carbapenems in Pulmonary, Urinary and Bloodstream Infections Diagnosed in Intensive Care Unit - BLUE¬-CarbA Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 2
- 主要终点
- mortality at D90 and infection recurrence during the ICU stay
研究概览
简要总结
The emergence and rapid worldwide spread of Extended- Spectrum Beta-Lactamase-producing enterobacteriaceae (ESBLE) both in hospital and community, led physicians, and notably intensivists, to prescribe more carbapenems, particularly in the most fragile patients such as ICU patients. Unfortunately, the increased carbapenem consumption favored the emergence of carbapenem resistance mechanisms. Moreover, several preliminary results suggest that carbapenem could markedly impact the human intestinal microbiota, Thus, reduction of carbapenem exposure is widely desired both by national and international antibiotic plans. Therefore, the use of rapid diagnostic tests evaluating bacterial resistance to reduce inappropriate exposure to carbapenems could be a relevant solution. Due to its good diagnostic performance, the betaLACTA® test could meet these objectives.
Experimental plan :
Randomized, open-labeled non-inferiority clinical trial involving an in vitro diagnostic medical device (close to a phase III study), comparing two parallel groups:
- Experimental group: early carbapenems de-escalation since the second dose, guided by results of the betaLACTA® test performed directly on the bacterial pellet from the microbiological sample positive on direct examination.
- Control group: carbapenems de-escalation guided by definitive results of the antibiotic susceptibility test obtained 48 to 72h after microbiological sampling (reference strategy).
详细描述
This study is conducted on ICU patients with a suspected pneumonia, primary blood-stream infection (BSI), and/or urinary tract infection (UTI).
The primary objective of the study is to demonstrate that in ICU infections treated empirically by carbapenems and documented with GNB on direct examination of a respiratory, urinary and/or blood sample(s), the early de-escalation guided by the results of the betaLACTA® test is not inferior to the reference strategy de-escalating on antibiotic susceptibility test (AST) results obtained 48-72h after sampling, in terms of mortality at D90 and infection recurrence in ICU.
The secondary objectives are to compare the early de-escalation guided by the betaLACTA® test results to the reference strategy de-escalating on the AST results on:
- The exposure to carbapenems.
- The total use of ICU and hospital resources and the cost-effectiveness.
- The occurrence of other infections.
- The colonization of the digestive tractus of patients with 3rd generation cephalosporins (3rdGC) resistant Gram-negative bacteria (GNB).
In addition, an ancillary study will be performed (only in participating centers from the Ile de France region) to compare :
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
- •ICU patients ≥18 years.
- •With a suspected pneumonia (according to CPIS definition), primary blood-stream infection (according to CDC definition), and/or urinary tract infection (according to IDSA Guidelines).
- •And presence of ≥2 GNB/field on direct examination of a respiratory sample (quantitative bronchial aspirate with an available volume ≥ 1mL), urinary sample or blood culture.
- •Leading to an empirical carbapenem prescription, not administered for more than 6 hours when considering the inclusion of the patient.
- •Written informed consent signed by the patient / the trustworthy person / the next-of-kin / close relative, or inclusion in case of emergency and written informed consent will been signed by the patient as soon as possible.
- •Patients affiliated to French social security.
排除标准
- •Pregnancy.
- •Allergy to beta-lactams.
- •Patients already treated with ongoing carbapenems for another documented infection, blocking carbapenem de-escalation.
- •Patients included in another interventional study.
- •Patients in whom a procedure of withdrawing life-sustaining treatment was decided before inclusion.
- •Moribund patients.
- •Patients with aplasia.
- •Patients under tutorship/curatorship or patient deprived of freedom
结局指标
主要结局
mortality at D90 and infection recurrence during the ICU stay
时间窗: Day 90
Composite endpoint combining 90-day mortality and percentage of infection recurrence (same GNB on the same site of infection) during the ICU stay (within the limit of 90 days). Recurrence will be defined a posteriori by 3 independent experts, blinded of the allocation group of patients in whom a suspected recurrence would have occurred, with predefined criteria.
次要结局
- Composition of intestinal microbiota at Day 0(from D0 to the end of the antimicrobial treatment of the infection leading to inclusion in the study, average 7-10 days)
- Colonization of the digestive tractus of patients with 3rd generation cephalosporins (3rdGC) resistant Gram-negative bacteria(From Day 0, through ICU discharge or until 28 days after inclusion in case of prolonged ICU stay)
- Exposure to carbapenems(from Day 0, through ICU discharge or until 28 days after inclusion in case of prolonged ICU stay)
- Total use of ICU and hospital resources and cost-effectiveness of early de-escalation compared to standard de-escalation.(from Day 0,throught hospital discharge or until 28 days after inclusion in case of prolonged ICU stay)
- Composition of intestinal microbiota at day 3(from D0 to the end of the antimicrobial treatment of the infection leading to inclusion in the study, average 7-10 days)
- Composition of intestinal microbiota after antibiotic exposur(from D0 to the end of the antimicrobial treatment of the infection leading to inclusion in the study, average 7-10 days)
- Occurrence of other infections.(From Day 0 to ICU discharge (within the limit of 90 days).)