PK/PD Relationship of CAZ/AVI and FOS in the Treatment of Patients With Infections Due to Carbapenem-resistant Enterobacterales (CRE)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 4
- 主要终点
- PK/PD efficacy targets for study drugs
研究概览
简要总结
A multicenter international prospective observational pharmacological study in adult patients (≥18 years) treated with ceftazidime/avibactam (CAZ/AVI) alone or with CAZ/AVI plus fosfomycin (FOS) for infection due to carbapenem-resistant Enterobacterales (CRE) (KPC and/or OXA-48).
详细描述
Gram-negative infections, particularly those caused by carbapenem-resistant Enterobacterales (CRE), have a dramatic impact on patient survival. Despite the introduction of new drugs in the last years have improved the outcome of patients with CRE infections, mortality and relapse rates are still relevant, especially in patients with high-risk source as pneumonia, and those in which the attainment of optimal exposure could be reduced by underlying renal disease. The use of combination regimen in these scenarios has been proposed. However, a standardized approach is still missing. Since several in vitro studies have highlighted the synergistic effect of fosfomycin (FOS) with different antibiotic classes, including cephalosporins such drug could be an appealing option in combination therapy for the management of CRE infections.
In particular, the primary aim of the study is to assess the probability of achieving a pre-defined target of efficacy in patients treated with ceftazidime/avibactam (CAZ/AVI) and/or FOS according to different modes of drug administration in patients with CRE infections.
Secondary aim is to assess the association between plasma drug concentration of both CAZ/AVI and FOS and patient response.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Signature of the informed consent
- •Age ≥ 18 years
- •Adult patients treated for ≥ 48 hours with CAZ/AVI or CAZ/AVI plus FOS for a microbiologically documented CRE infection
排除标准
- •Polymicrobial/mixed infections with exception of cases with multiple Enterobacterales susceptible to study drugs
结局指标
主要结局
PK/PD efficacy targets for study drugs
时间窗: From enrollment (treatment onset) to 48 and 72 hours after starting treatment
The primary endpoint will be the attainment of the pre-defined PK/PD target of efficacy at 48 and 72 hours after starting treatment for Carbapenem-resistant Enterobacterales (CRE) infection
次要结局
- Microbiological eradication(From day 0 (day of index positive culture) and day 7)
- All-cause mortality(From enrollment to the end of the follow-up at three months)
- Difference in SOFA score(From day 0 (day of index positive culture) and day 7)
- Trend of C-Reactive Protein (CRP) and Procalcitonin (PCT)(From day 0 (day of index positive culture) and day 7)
- Relapse and/or reinfection(From enrollment to the end of the follow-up at three months)