A Phase III Randomised Controlled Trial of Continuous Beta-lactam Infusion Compared With Intermittent Beta-lactam Dosing in Critically Ill Patients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 7,203
- 试验地点
- 195
- 主要终点
- All-cause mortality
研究概览
简要总结
The purpose of this study is to find out whether continuous infusion of beta-lactam antibiotics or intermittent infusion or beta-lactam antibiotics, offers more health advantages to patients or if there is no difference.
The investigators will be looking to see whether patients receiving beta-lactams via one administration method or the other have a better chance of recovering from their illness. They will also be looking at long term outcomes such as quality-of-life and healthcare resource use.
Sepsis is caused by toxic substances (toxins) from bacteria and other organism entering the bloodstream from a site of infection. In some people, the infection can progress to sepsis and septic shock where the functions of organs in the body are affected. Patients suffering from sepsis and septic shock are commonly managed in the intensive care unit (ICU) where they are prescribed antibiotics as standard therapy, as well as other therapies to support the functions of the body.
Beta-lactam antibiotics are a group of antibiotics commonly used to treat infection in patients with sepsis and septic shock.
Currently, beta-lactam antibiotics are most commonly given to patients be intermittent infusions, that is, given at regular intervals throughout 24 hours. New research suggests that giving beta-lactam antibiotics as a continuous infusion may mean that antibiotic concentrations in the blood remain more consistent and may be more effective at killing bacteria.
However, the benefit to the patient by giving beta-lactams via continuous infusion has not been tested in a high-quality, large clinical trial.
详细描述
Aim To conduct a multicentre randomised, controlled trial (RCT) to determine whether continuous infusion of a beta-lactam antibiotic (piperacillin-tazobactam or meropenem) results in decreased all cause Day 90 mortality compared with intermittent beta-lactam antibiotic infusion in critically ill patients with sepsis.
Hypothesis The BLING III Study will test the hypothesis that patients managed in the ICU with sepsis, the administration of beta-lactam antibiotics via continuous infusion decreases Day 90 mortality compared with intermittent infusion Design This BLING III study is a prospective, multicentre, open, phase III, RCT. Participants commenced on one of two beta-lactam antibiotics (piperacillin-tazobactam or meropenem) will be randomised to receive the beta-lactam antibiotic via either continuous infusion or intermittent infusion over 30 minutes for the treatment course while in the ICU for up to 90 days after randomisation. For participants where the beta-lactam antibiotic is subsequently changed from piperacillin-tazobactam to meropenem or vice versa for ongoing treatment of the infectious episode, the new prescription will continue to be administered in the allocated method (continuous infusion or intermittent infusion over 30 minutes).
Permuted block randomisation with variable block sizes and stratified by site will be conducted via a password-protected, secure web-based interface.
The primary endpoint for this trial will be death from all causes at 90 days.
7,000 patients will be enrolled into this study from approximately 70 ICUs worldwide, with approximately 35 ICUs in Australian and New Zealand hospitals.
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
- •Documented site of infection or strong suspicion of infection
- •At the time of the assessment of suitability for the study, the treating physician expects the patient will require treatment in the ICU that extends beyond the next calendar day
- •The treating physician has chosen piperacillin-tazobactam or meropenem to treat the episode of infection
- •The treating physician is uncertain if administration of the chosen antibiotic by intermittent or continuous infusion is superior
- •One or more organ dysfunction entry criteria in the previous 24 hours
- •i. Mean arterial pressure < 60 mmHg for at least 1 hour
- •ii. Vasopressors required for > 4 hours
- •iii. Respiratory support using supplemental high flow nasal prongs, continuous positive airway pressure, bilevel positive airway pressure or invasive mechanical ventilation for at least 1 hour
- •iv. Serum creatinine concentration > 220 µmol/L
排除标准
- •Age less than 18 years
- •Receipt of piperacillin-tazobactam or meropenem for more than 24 hours during current infectious episode
- •Patients who are known or suspected to be pregnant
- •Patient has a known allergy to piperacillin-tazobactam or meropenem or penicillin
- •Receiving renal replacement therapy at the time of assessment for eligibility
- •The treating physician is not committed to provision of advanced life-support, including mechanical ventilation, dialysis and vasopressor administration, for at least the next 48 hours
- •Death is deemed imminent and inevitable
- •The patient has previously been enrolled in BLING III
结局指标
主要结局
All-cause mortality
时间窗: 90 Days after randomisation
Patient mortality status assessed at 90 days after randomisation
次要结局
- Clinical Cure(Day 14 post randomisation)
- New acquisition, colonisation or infection(up to 14 days post randomisation or hospital discharge, whichever is sooner)
- All cause ICU mortality(up to 90 days)
- All cause hospital mortality(up to 90 days)