Ventilator associated pneumonia (VAP) that occurs in critically ill patients who receive mechanical ventilation is a serious nosocomial complication that can prolong hospitalization, increase mortality, and reduce long term quality of life and cognitive function. Modification of the design of the endotracheal tube (ETT) that allows continuous aspiration of subglottic secretions through an extra port positioned between the cuff and the vocal cords may prevent leakage of contaminated secretions around the cuff and thereby reduce the risk of VAP. The replacement of the standard polyvinylchloride (PVC) cuff material with polyurethane (PU) may further protect from microaspiration. We previously successfully completed a randomized pilot controlled trial of two modified ETTs in patients requiring emergency intubation to establish the feasibility of a larger trial to address the long-term safety and effectiveness of modified ETTs. We propose a Phase II, randomized, controlled trial that will equally randomize patients requiring emergency endotracheal intubation to receive either a PU-cuffed ETT equipped with continuous aspiration of subglottic secretions (PU-CASS-ETT, n=537) or a conventional, PVC-cuffed ETT (PVC-ETT, n=537). Similar to the pilot study, this trial will be conducted under Exception from Informed Consent (EFIC) in the four adult ICUs at Oregon Health & Science University. The units of randomization will be the intubation kits which will contain in a concealed manner one of the two ETT models provided in duplicate in two appropriate gender-specific sizes. The trial primary aim is to determine if PU-CASS-ETT is as safe as PVC-ETT and if long-term patient quality of life and cognitive function are better in PU-CASS-ETT, compared with PVC-ETT. The co-primary safety endpoint is the evaluation of the safety profile based on upper airway-related complications and laryngeal dysfunction collected via in person interview, compared with the PVC-ETT, at 6 months after randomization. We will also monitor any device-related adverse events. Our co-primary effectiveness endpoint is quality of life, as measured by the Medical Outcomes Study 36-item Short-Form General Health Survey, and cognitive function, as assessed by the National Alzheimer Coordinating Center's Uniform Data Set, at 6 months after randomization. The secondary endpoints include the incidence of infection-related ventilator associated conditions (IVAC) and ventilator associated events (VAEs), as defined by the Center for Disease Control, respiratory antibiotics use, incidence of ?clinical? VAP, 28-day ventilator-free days, mean daily Sequential Organ Failure Assessment (SOFA) score, length of ICU and hospital stay, and mortality up to six months will serve to evaluate other clinical meaningful consequences resulting from the occurrence of VAP. Furthermore, the study will perform economic evaluation (cost-consequence approach) of quality of life, healthcare resource utilization and cost for hospitals. Primary and secondary endpoints will be compared between the PU-CASS-ETT and PVC-ETT groups, using an intention-to-treat approach.
We propose a Phase II randomized, controlled trial that will equally randomize 1,074 patients requiring emergency endotracheal intubation to receive either a polyurethane-cuffed endotracheal tube equipped with continuous aspiration of subglottic secretions designed to prevent ventilator-associated pneumonia or a conventional, polyvinylchloride-cuffed endotracheal tube. Using a pragmatic approach, we will determine if the modified endotracheal tube is as safe as the conventional endotracheal tube, and if by reducing the incidence of ventilator-associated pneumonia, it improves long-term quality of life and cognitive function, thus providing much needed evidence supporting decision-making. This study is relevant to public health because over 800,000 patients receiving mechanical ventilation in the United States each year are at risk of ventilator-associated pneumonia - a nosocomial infection developing during mechanical ventilation that is associated with substantial disease burden, resource utilization, and long- term reduction in quality of life and cognitive impairment.
