Oral Chlorhexidine effect on ICU mortality and ventilator-associated pneumonia

描述（由申请人提供）：医院获得性肺炎是第二常见的医院获得性感染和最常见的重症监护病房感染。它与显著的发病率和死亡率有关。口咽内容物误吸被认为是肺炎的主要危险因素，特别是在机械通气患者中。口服抗菌药物如氯己定是否能降低普通重症监护病房患者的肺炎风险仍存在争议。拟议的III期临床试验将是一项为期五年、四中心的安慰剂对照随机临床试验，以氯己定口服应用为干预措施。该研究将通过使用良好验证的临床和主要结果评分标准，在普通ICU人群研究样本中扩展先前的发现。拟议的试验将用于评估535名对照组患者和535名干预组患者的呼吸机相关性肺炎（VAP）和/或死亡率的复合主要结局。一项为期2年的计划拨款被要求用于改进研究设计和方法，制定操作程序手册，改进患者招募方法，组织潜在的研究中心以实现方法和诊断标准的标准化，并建立管理和监督委员会。来自四个临床站点和数据协调中心的人员将作为临床试验计划委员会的一部分参加这些活动。III期临床试验将是第一个正确评估氯己定口服应用对各种ICU入院指征（包括外科、内科和神经学）机械通气患者肺炎和/或死亡率以及相关发病率结果的影响的结果研究。它可能为改变卫生保健政策提供证据，表明一种简单、廉价的口腔保健预防性干预可以降低与院内肺炎相关的发病率、死亡率和成本。

DESCRIPTION (provided by applicant): Nosocomial pneumonia is the second most common hospital-acquired infection and most common intensive care unit infection. It is associated with significant morbidity and mortality. Aspiration of oropharyngeal contents is considered a major risk factor for pneumonia, especially in mechanically ventilated patients. Whether application of oral antimicrobial agents such as chlorhexidine reduces the risk of pneumonia in the general intensive care unit patient population remains controversial. The proposed Phase III clinical trial will be a five-year, four-center placebo-controlled randomized clinical trial with a chlorhexidine oral application as the intervention. The research will extend previous findings in a general ICU population study sample by using well-validated clinical and scoring criteria for major outcomes. The proposed trial will be powered to evaluate a composite primary outcome of ventilator-associated pneumonia (VAP) and/or mortality with 535 patients in the control group and 535 patients in the intervention group. A 2 year planning grant is requested to refine the study design and methodology, develop a Manual of Operating Procedures, refine patient recruitment approaches, organize potential study centers for standardization of approach and diagnostic criteria, and establish administrative and monitoring committees. Personnel from the four clinical sites and the data coordinating center will participate in these activities as part of the Clinical Trial Planning Committee. The Phase III clinical trial would be the first outcome study properly powered to evaluate the effect of chlorhexidine oral application on pneumonia and/or mortality, and associated morbidity outcomes in mechanically ventilated patients with various indications for ICU admission (including surgical, medical, and neurological). It may provide evidence for changing health care policy by showing that a simple, inexpensive oral care preventive intervention reduces the morbidity, mortality, and costs associated with nosocomial pneumonia.