Randomised, Open-Label Clinical Trial on The Efficacy of Colistin Plus Rifampicin Treatment Versus Colistin Alone for Severe Infections Due to Multidrug-Resistant Acinetobacter Baumannii
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 210
- 主要终点
- All cause mortality
研究概览
简要总结
Acinetobacter baumannii causes severe infections (pneumonia, bacteremia, organ space) with high lethality in hospitalised critically ill patients. It can acquire resistance to all classes of antibiotics (multidrug resistance, MDR) except an 'old' drug, colistin, which may be the only therapeutic option. However, colistin is not registered for this indication. The addition of rifampicin to colistin has been shown to be synergistic in vitro, and may be promising in vivo, but this combination has not been studied in comparison with colistin alone.
The purpose of this randomised, open-label, multicentre clinical trial is to assess whether the association of colistin and rifampicin reduces significantly the mortality of patients with severe MDR A. baumannii infections compared with colistin alone.
The trial will enroll 210 patients from intensive care units (ICU) of five tertiary care hospitals where MDR A. baumannii infection is endemic with epidemic phases. Patients will be randomly allocated to either colistin alone (control arm) or colistin plus rifampicin (experimental arm).
Primary end point is overall mortality, defined as death occurring within 30 days from randomisation.
Secondary end points will be disease-specific death, microbiological eradication, hospitalization length, emergence of resistance to colistin during treatment.
详细描述
This study is designed as a multicentre open-label, parallel randomised, controlled trial. Patients will be randomly allocated to two treatment arms: 1) colistin alone (control arm); 2) colistin, plus rifampicin (experimental arm). The study will be carried out over 2 years according to the principles of good clinical practice.
The study population is represented by adult hospitalised patients with severe nosocomial infections due to multi-drug resistant A. baumannii, susceptible to colistin. It will be performed in intensive or sub-intensive care units of 5 Italian clinical centres where MDR A. baumannii infection is endemic with epidemic phases. All adult subjects, irrespective of age, will be included in the study, thus also elderly subjects will be eligible. Large eligibility criteria are warranted by the pragmatic approach of the study, the severe prognosis of these patients and the lack of effective alternative treatments.
Enrollment procedure: At the time of A. baumannii isolation, inclusion and exclusion criteria will be checked by the pertinent centre.
Once obtained the informed consent, subjects will be randomized to treatment. No patient may be enrolled in a centre before the formal approval of the Ethics Committee of that Institution.
Accrual time: according to the sample size estimate (see below) and based on the current incidence of MDR A. baumannii severe infections of 12-14 cases per month in the five participating centres, the accrual time will last approximately 18 months to achieve the planned sample size.
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
- •clinical and microbiological evidence of a severe infection due to multi-drug resistant A. baumannii during hospitalization
- •susceptibility of the A. baumannii isolate to colistin (MIC < or =2 mg/l).
排除标准
- •age below 18 years
- •treatment with one of the study drugs prior to the diagnosis of A. baumannii infection
- •severe liver dysfunction
- •history of prior hypersensitivity to the study drugs
研究组 & 干预措施
Colistin
Colistin alone, 2 million units every 8 hours intravenously or according to renal function
干预措施: Colistin (Drug)
Colistin plus Rifampicin
Colistin, 2 million units every 8 hours intravenously or according to renal function, plus Rifampicin, 600 mg every 12 hours intravenously
干预措施: Colistin (Drug)
Colistin plus Rifampicin
Colistin, 2 million units every 8 hours intravenously or according to renal function, plus Rifampicin, 600 mg every 12 hours intravenously
干预措施: Rifampicin (Drug)
结局指标
主要结局
All cause mortality
时间窗: 30 day
The study primary outcome is patient overall mortality, defined as death occurring during hospitalisation or within 30 days from randomization.
次要结局
- Microbiological eradication(30 day)
- Disease-specific death(30 days after randomization)
- Hospitalization length(From admission to hospital discharge, an average of 30 days)
- Emergence of resistance to colistin(From day 1 to the end of study evaluation, 30 days after randomization)
- Toxicity(From day 1 to the end of treatment evaluation, performed between day 10 and day 21)
研究者
Riccardo Utili
Professor
University of Campania "Luigi Vanvitelli"