Empirical Meropenem versus Piperacillin/Tazobactam for Adult Patients with Sepsis (EMPRESS) trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 400
- 试验地点
- 1
- 主要终点
- All-cause mortality at day 30 after randomisation
研究概览
简要总结
To assess the effects of empirical meropenem versus piperacillin/tazobactam on mortality and other patient-important outcomes in critically ill adults with sepsis.
详细描述
Background Piperacillin/tazobactam and meropenem are commonly used as empirical agents for patients with sepsis or septic shock. In a recent systematic review comparing empirical and/or definitive treatment with piperacillin/tazobactam versus meropenem for patients with severe bacterial infections, including sepsis and septic shock, it was shown that piperacillin/tazobactam may be associated with less favourable outcomes based on low or very low certainty of evidence. At present, it is unclear if piperacillin/tazobactam and meropenem are equally effective and safe for adults with sepsis.
Objectives To assess the effects of empirical meropenem vs. piperacillin/tazobactam on mortality and other patient-important outcomes in critically ill adults with sepsis.
Design Investigator-initiated, international, parallel-group, randomised, open-label, adaptive clinical trial with an integrated feasibility phase. The EMPRESS trial will employ adaptive stopping rules to increase the chance that the trial will be conclusive and response-adaptive randomisation to increase each participant's chance of being randomised to the superior intervention arm.
Inclusion and exclusion criteria We will screen all adult patients who are critically ill with sepsis and who have indication for empirical treatment with meropenem or piperacillin/tazobactam. We will exclude patients with preceding intravenous treatment with meropenem or piperacillin/tazobactam for 24 hours or more; known pregnancy; known hypersensitivity or allergy to beta-lactam antibiotics; suspected or documented central nervous system infection; known infection or colonialisation with microorganism with acquired resistance to meropenem or piperacillin/tazobactam; current use of valproate; co-enrolment in other interventional trial where protocols collide; previous randomisation in EMPRESS; informed consent following inclusion expected to be unobtainable; and patients who are under coercive measures.
Experimental intervention IV meropenem 1 g three times daily for up to 30 days.
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 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Age ≥ 18 years
- •Sepsis (including septic shock) defined according to the Sepsis-3 criteria, i.e., suspected or documented infection and an acute increase of ≥ 2 points in the Sequential Organ Failure Assessment (SOFA) score (a marker of acute organ dysfunction)
- •Critical illness defined as use of at least one of the following: a. Invasive mechanical ventilation b. Non-invasive ventilation c. Continuous use of continuous positive airway pressure (CPAP) for hypoxia d. Oxygen supplementation with an oxygen flow of ≥ 10 litres (L)/minute independent of delivery system and total flows e. Continuous infusion of any vasopressor or inotrope (excluding strictly procedure-related infusions)
- •Clinical indication for empirical treatment with either meropenem or piperacillin/tazobactam
排除标准
- •Preceding intravenous treatment with meropenem or piperacillin/tazobactam for > 24 hours prior to screening
- •Patient under coercive measures
- •Fertile women < 60 years of age with known pregnancy or positive urine human gonadotropin (hCG) or plasma hCG
- •Known hypersensitivity or allergy to beta-lactam antibiotics
- •Suspected or documented central nervous system infection
- •Known infection/colonialization with microorganism with acquired resistance against meropenem or piperacillin/tazobactam within the previous 3 months (e.g., ESBL-, AmpC- or carbapenemase-producing bacteria)
- •Current or planned use of valproate within 30 days from randomisation
- •Patient included in another interventional trial where co-enrolment with EMPRESS is not permitted
- •Previously randomised into the EMPRESS trial
- •Informed consent following inclusion expected to be unobtainable
结局指标
主要结局
All-cause mortality at day 30 after randomisation
All-cause mortality at day 30 after randomisation
次要结局
- Number of participants with one or more serious adverse reactions (SARs, defined as anaphylactic shock to IV piperacillin/tazobactam or meropenem, invasive fungal infection, pseudomembranous colitis, or toxic epidermal necrolysis) within 30 days of randomisation
- Number of participants with new isolation precautions due to one or more resistant bacteria within 30 days of randomisation
- Days alive without life support (i.e., invasive mechanical ventilation, circulatory support, or renal replacement therapy [including days in between intermittent renal replacement therapy]) from randomisation to day 30
- Days alive and out of hospital from randomisation to day 30
- Days alive without life support (i.e., invasive mechanical ventilation, circulatory support, or renal replacement therapy [including days in between intermittent renal replacement therapy]) from randomisation to day 90
- Days alive and out of hospital from randomisation to day 90
- All-cause mortality at day 90
- All-cause mortality at day 180
- HRQoL at day 180 using EQ-5D-5L index values
- HRQoL at day 180 using EQ VAS
研究者
Morten Hylander Møller
Scientific
Rigshospitalet