Pilot Trial of Tubes to Prevent VAP

描述(由申请人提供)：这项初步研究的目的是为规划和确定进行两种专门设计的用于预防呼吸机相关性肺炎(VAP)的大型、随机、比较有效性试验的可行性提供数据。改变位于气管内的ETT气囊的材料和设计，和/或通过位于气囊和声带之间的额外端口持续吸入声门下分泌物，可以防止气囊周围受污染的分泌物泄漏，从而降低VAP的风险。研究人员正在计划一项第三阶段的随机对照试验，比较聚亚安酯袖套气管导管(PUC-ETT)、也允许持续吸入声门下分泌物的聚氨酯袖套导管(PUC-CASS-ETT)和传统的聚氯乙烯袖套气管导管(PVC-ETT)在机械通气呼吸衰竭患者中的有效性。在启动第三阶段试验之前，有必要进行一项较小规模的试点研究，以确定可行性并收集有关终点的数据，以便为最终试验确定参保率和项目样本量。为了计划的目的，作为VAP的替代品，气管的细菌定植将从日常定量培养中进行评估，以允许估计两个研究装置的效果大小。次要目标包括确定这些ETT的放置是否对其他重要的临床终点有有益影响，包括无呼吸机天数、28天死亡率、重症监护病房和住院时间，以及通过评估ETT移除后持续存在的上呼吸道并发症来确定装置的安全性。大约90名危重患者在院内或院外接受紧急气管插管，将随机接受三种ETT中的一种。VAP的诊断将使用基于支气管肺泡灌洗培养的客观标准。将使用多方面的方法评估导管的安全性，包括对喉部功能障碍的短期客观测量，以及通过电话访谈、出院后出院后对上呼吸道问题的长期主观和客观评估，以及记录与设备相关的不良事件。 公共卫生相关性：这项初步研究将为计划提供数据，并确定进行两种改良气管内导管的明确比较有效性试验的可行性，这两种改良气管导管旨在减少声门下分泌物的微吸入，以降低呼吸机相关性肺炎的风险。这项研究将在患有急性呼吸衰竭的不同危重患者中进行，下呼吸道细菌的定植将被用作呼吸机相关肺炎风险的替代。这项先导性研究的结果将被用来估计更大规模的第三阶段试验的样本量和患者登记率。

DESCRIPTION (provided by applicant): The objective of this pilot study is provide data for planning and to establish the feasibility of performing a large, randomized, comparative effectiveness trial of two specially designed airway tubes (endotracheal tubes; ETTs) for the prevention of ventilator-associated pneumonia (VAP). Modification of the material and design of the ETT cuff that is positioned in the trachea, and/or continuous aspiration of subglottic secretions through an extra port positioned between the tube cuff and the vocal chords may prevent leakage of contaminated secretions around the cuff and thereby reduce the risk of VAP. The investigators are planning a phase III, randomized, controlled trial comparing the effectiveness of a polyurethane-cuffed endotracheal tube (PUC-ETT), a polyurethane-cuffed tube that also allows continuous aspiration of subglottic secretions (PUC-CASS-ETT), and a conventional, polyvinylchloride-cuffed endotracheal tube (PVC-ETT) in mechanically ventilated patients with respiratory failure. Prior to initiating the Phase III trial, a smaller pilot study is necessary in order to establish feasibility and to gather data on endpoints in order to establish enrollment rates and project sample size for the definitive trial. For the purposes of planning, a surrogate for VAP, bacterial colonization of the trachea will be assessed from daily quantitative cultures to allow estimation of effect size for the two study devices. Secondary aims include the determination of whether the placement of these ETTs has beneficial effects on other important clinical endpoints, including ventilator-free days, 28-day mortality, intensive care unit and hospital length of stay, and to determine the safety profile of the devices by assessment of upper airway complications persisting after removal of the ETT. Approximately 90 critically ill patients undergoing emergency tracheal intubation in- or out-of-hospital will be randomized to receive one of the three ETTs. VAP will be diagnosed using objective criteria, based on cultures from bronchoalveolar lavage. The safety profile of the tubes will be evaluated using a multi-faceted approach, including short-term objective measures of laryngeal dysfunction and long-term subjective and objective assessment of upper airway problems via phone interview post-hospital discharge, and recording of device-related adverse events. PUBLIC HEALTH RELEVANCE: This pilot study will provide data for planning and establish the feasibility of performing a definitive comparative effectiveness trial of two modified endotracheal tubes designed to reduce microaspiration of subglottic secretions in reducing the risk of ventilator-associated pneumonia. The study will be performed in a diverse population of critically ill patients with acute respiratory failure, and colonization of the lower airways with bacteria will be used as a surrogate for the risk of ventilator- associated pneumonia. The results from this pilot study will be used to estimate sample size and patient enrollment rates for the larger, Phase III trial.