Cefiderocol and Ampicillin-sulbactam vs. Colistin or Colistin-meropenem for Carbapenem Resistant Acinetobacter Baumannii Bacteremia or Hospital-acquired Pneumonia: Controlled Clinical Study With Historical Controls (CASCADE)
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 734
- 试验地点
- 3
- 主要终点
- All cause mortality
研究概览
简要总结
Patients with bloodstream infections, hospital acquired pneumonia or ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii (CRAB) treated with cefiderocol combined with ampicillin sulbactam will be compared to patients treated treated with colistin alone or colistin combined with meropenem.
详细描述
This will be a prospective controlled clinical study with historical controls.
In the prospective CASCADE study consecutive consenting patients with bloodstream infections, hospital acquired pneumonia or ventilator-associated pneumonia will be treated with cefiderocol combined with ampicillin sulbactam in 3 hospitals in Israel and 2 hospitals in Italy, all endemic for CRAB. We plan to recruit 150 patients into this prospective studies.
The CASCADE cohort will be compared to patients treated for the same types of infection in two recently completed randomized controlled trials (AIDA and OVERCOME). These trials compared between treatment with colistin vs. treatment with colistin-meropenem combination therapy, both finding no difference between treatment groups among patients with carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia. Thus, patients in CASCADE will be compared to all patients with CRAB bloodstream infections, hospital acquired pneumonia or ventilator-associated pneumonia in these randomized controlled trials.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults >18 years with bacteremia or hospital-acquired pneumonia (HAP)/ ventilator-associated pneumonia (VAP) (Table 3) caused by carbapenem-resistant A. baumannii (CRAB) (meropenem and/ or imipenem minimal inhibitory concentration (MIC) >8 μg/mL) susceptible to cefiderocol (disc zone diameter >=17 mm, corresponding to an MIC <2 μg/mL). We will include CRAB regardless of colistin, ampicillin-sulbactam, minocycline, tigecycline, trimethoprim/sulfamethoxazole and/or aminoglycoside susceptibility of the isolate. Attribution of the HAP/ VAP to CRAB will be allowed with isolation of CRAB from any respiratory sample within 7 days prior to the clinical diagnosis of pneumonia.
排除标准
- •More than 72 hours of therapy with in-vitro coverage against the CRAB within 96 hours of enrolment
- •Polymicrobial carbapenem-susceptible infections: growth of other pathogens susceptible to carbapenems, or another beta-lactam, deemed clinically-significant by the treating physicians in blood or sputum (with HAP/ VAP). We will allow recruitment of patients with other carbapenem-resistant Gram-negative bacteria
- •CRAB susceptible any beta-lactam other than cefiderocol
- •Coronavirus 2019 (COVID-19) co-infection
- •Immediate-type hypersensitivity to penicillin
- •Pregnant women
- •Previous participation in the trial
- •Lack of informed consent, considering the procedures acceptable to ethics committees per locale, including deferred consent
- •Infection requiring treatment for over 14 days, at the discretion of the investigators
- •Life expectancy less than 24 hours or expected futility of antibiotic treatment
研究组 & 干预措施
Cefiderocol + ampicillin-sulbactam
Cefiderocol 2 gram intravenous (IV) q8 hours and ampicillin-sulbactam 3 gram IV q6 hours for patients with normal creatinine clearance, both administered as extended infusion of 3 hours. Dosing adjusted according to reduced and augmented renal clearance and to renal replacement therapies.
干预措施: Cefiderocol (Drug)
Cefiderocol + ampicillin-sulbactam
Cefiderocol 2 gram intravenous (IV) q8 hours and ampicillin-sulbactam 3 gram IV q6 hours for patients with normal creatinine clearance, both administered as extended infusion of 3 hours. Dosing adjusted according to reduced and augmented renal clearance and to renal replacement therapies.
干预措施: Ampicillin-sulbactam (Drug)
Colistin or colistin + meropenem
Colistin 9 million units (MIU) intravenous (IV) loading dose followed by 4.5 MIU for patients with normal creatinine clearance +/- meropenem 2 gram IV administered as extended infusion of 3 hours. Dosing adjusted according to reduced and augmented renal clearance and to renal replacement therapies.
干预措施: Colistin (Drug)
Colistin or colistin + meropenem
Colistin 9 million units (MIU) intravenous (IV) loading dose followed by 4.5 MIU for patients with normal creatinine clearance +/- meropenem 2 gram IV administered as extended infusion of 3 hours. Dosing adjusted according to reduced and augmented renal clearance and to renal replacement therapies.
干预措施: Meropenem (Drug)
结局指标
主要结局
All cause mortality
时间窗: 28 days
Death from any cause
次要结局
- All cause mortality(14 days)
- Microbiological failure(Day 5-7)
- Adverse event - renal failure(28 days)
- Decline in functional capacity(28 days)
- Resistance development to cefiderocol(28 days)
- Adverse event - Clostridiodes difficile infection(28 days)
- Clinical failure(Day 10-14)
- Hospital stay(28 days)
- Adverse event - Acute liver injury(28 days)