GRam Stain-guided Antibiotics ChoicE for Ventilator-Associated Pneumonia (GRACE-VAP) Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 206
- 试验地点
- 12
- 主要终点
- Clinical cure of VAP
研究概览
简要总结
Background: Optimising the use of antibiotic agents is a pressing challenge to overcoming the rapid emergence and spread of multidrug-resistant pathogens in intensive care units (ICUs). Although Gram staining may possibly provide immediate information for predicting pathogenic bacteria, Gram stain-guided initial antibiotic treatment is not well established in the ICU setting. The investigators planned the GRam stain-guided Antibiotics ChoicE for Ventilator-Associated Pneumonia (GRACE-VAP) trial to investigate whether Gram staining can safely restrict the use of broad-spectrum antibiotics in patients with ventilator-associated pneumonia (VAP), which is one of the most common hospital-acquired infections in ICUs.
Methods/Design: The GRACE-VAP trial is a multicenter, randomised, open-label parallel-group trial to assess the non-inferiority of Gram stain-guided initial antibiotic treatment to guidelines-based initial antibiotic treatment for the primary endpoint of clinical cure rate in patients with VAP. Secondary endpoints include the coverage rates of initial antibiotic therapies, the selected rates of anti-pseudomonal agents and anti-methicillin-resistant Staphylococcus aureus (MRSA) agents as initial antibiotic therapies, 28-day all-cause mortality, ICU-free days, ventilator-free days, and adverse events. Participants are randomly assigned to receive Gram stain-guided treatment or guidelines-based treatment at a ratio of 1:1. In the Gram stain group, results of Gram staining of endotracheal aspirate are used to guide the selection of antibiotics. In the guidelines group, the combination of an anti-pseudomonal agent and anti-MRSA agent are administered. A total sample size of 200 was estimated to provide a power of 80% with a 1-sided alpha level of 2.5% and a non-inferiority margin of 20%, considering 10% non-evaluable participants.
Discussion: The GRACE-VAP trial is expected reveal whether Gram staining can reduce the use of broad-spectrum antibiotics without impairing patient outcomes and thereby provide evidence for an antibiotics selection strategy in patients with VAP.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients undergoing mechanical ventilation in the ICU
- •Patients undergoing mechanical ventilation for at least 48 hours
- •Patients diagnosed as having VAP, which is defined by a modified clinical pulmonary infection score of 5 or more
排除标准
- •Patients having an allergy to study medications
- •Pregnant patients
- •Patients discharged from ICU
- •Patients diagnosed as having heart failure or atelectasis
- •Patients administered antibiotics for more than 24 hours when they meet the inclusion criteria
- •Patients declined to provide full life support
- •Patients judged as inappropriate at the discretion of the study physician.
研究组 & 干预措施
Gram stain-guided therapy group
The results of Gram staining of endotracheal aspirate are used to guide the selection of antibiotics. The results of the Gram stains are categorised as Gram-positive cocci (GPC) chains, GPC clusters, Gram-positive bacilli (GPB), Gram-negative rods (GNR), or a combination of these. A non-pseudomonal beta-lactam antibiotic is selected when the Gram stain of the endotracheal aspirate shows only GPC chains and/or GPB. An anti-MRSA agent is selected when the Gram stain results show GPC clusters without GNR. An anti-pseudomonal agent is selected when the Gram stain results show GNR without GPC clusters. The combination of an anti-pseudomonal agent and an anti-MRSA agent is selected when the Gram stain results show both GPC clusters and GNR.
干预措施: Gram stain-guided antibiotic choice (Drug)
Guidelines-based therapy group
Patients are administered the combination of an anti-pseudomonal agent and anti-MRSA agent according to the Infectious Disease Society of America and the American Thoracic Society (IDSA/ATS) guidelines because 47.7% of S. aureus isolates are MRSA in Japanese ICUs
干预措施: Guidelines-based antibiotics choice (Drug)
结局指标
主要结局
Clinical cure of VAP
时间窗: up to 22 days
Cure is defined as completion of antibiotic therapy within 14 days, improvement or lack of progression of baseline radiographic findings at the end of therapy (EOT), and resolution of signs and symptoms of pneumonia at the follow-up/test of cure visit (FU/TOC) conducted 7 days after EOT. Failure is defined as administration of study medication for 15 days or more, progression of radiological signs of pneumonia at EOT, or relapsed pneumonia at FU/TOC.
次要结局
- Select of anti-pseudomonal agents as initial antibiotic therapies(on day 1)
- Select of anti-MRSA agents as initial antibiotic therapies(on day 1)
- Organ failure control(up to 14 days)
- Renal function(up to 14 days)
- Ventilator-free days(up to 28 days)
- Duration of antibiotic therapies(up to 28 days)
- Coverage of initial antibiotic therapies(on day 1)
- 28-day mortality(up to 28 days)
- ICU-free days(up to 28 days)
- Need of escalation or de-escalation of antibiotic therapies(up to 28 days)
- Adverse events related to antibiotics(up to 7 days after the end of therapy)
- Inflammation marker(up to 14 days)
研究者
Jumpei Yoshimura, MD
Dr.
Osaka General Medical Center