Ceragenin Coated Endotracheal Tubes for the Prevention of Ventilator Associated Pneumonia

Study Overview
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Brief Summary
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Critically ill patients are at high risk of acquiring pneumonia during the time that they are mechanically ventilated. This is known as ventilator-associated pneumonia (VAP). VAP results in increased duration of mechanical ventilation, increased ICU and hospital stay, increased risk of death and increased health care costs. VAP occurs in 20% of patients and it is estimated that each case of VAP costs the health care system $10 to 15,000 Canadian. Because of its impact on patient outcomes and the health care system, VAP is regarded as an important patient safety issue and there is an urgent need for better prevention strategies. Invasive mechanical ventilation requires the passage of an endotracheal tube (ETT) through the pharynx which is frequently colonized with bacterial pathogens and a bio-film rapidly forms on the ETT. VAP results either from aspiration of contaminated oropharyngeal secretions or from aspiration of bacteria from the bio-film. In this project, the efficacy of a novel ETT coated with an antibiotic compound that has been shown to reduce the formation of bio-film and pathogen colonization will be tested. Preliminary evidence as to whether utilization of this novel ETT reduces the occurrence of VAP and improves patient outcomes will be obtained through the conduct of a pragmatic, prospective, longitudinal, interrupted time, cross-over implementation study.

Detailed Description
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The innovation that is being studied is a novel antibiotic coated endotracheal tube (ETT) for the prevention of ventilator associated pneumonia (VAP) in critically ill, mechanically ventilated patients. The novel ETT is the CeraShield ETT consisting of a standard ETT with an antimicrobial hydrophilic coating containing ceragenins (CSAs) on the inner and outer lumen of the device, as well as the inflatable cuff. The CSA coating on the CeraShield protects it from microbial colonization and bio-film growth. The CSA ETT is otherwise equivalent to standard ETT tubes currently in use and is licensed in Canada for clinical use as a Class 2 device. It is hypothesized that CSA coated ETTs will reduce the incidence of Ventilator Associated Pneumonia and improve clinical outcomes including antibiotic utilization when compared to ETTs currently in use. It is hypothesized that a definitive cluster randomized multi-center study is feasible and supported by the data from this study. To test the hypotheses, an Interrupted Time Series Cross-Over Implementation Study will be used to provide preliminary evidence of the efficacy of the CeraShield ETT compared to the ETT currently used at the study center in critically ill mechanically ventilated patients. This study will inform and be modified to conduct a future large multi-center cluster randomized study.

Official Title
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Ceragenin Coated Endotracheal Tubes for the Eradication of Ventilator Associated Pneumonia - A Prospective, Longitudinal, Cross-over, Interrupted Time, Implementation Study (CEASE VAP Study)

Conditions
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Ventilator Associated Pneumonia

Intervention / Treatment
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* Device: CeraShield Endotracheal Tube
* Device: Endotracheal tube with subglottic secretion drainage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult critically ill patients with respiratory failure requiring intubation Exclusion Criteria: Admission to hospital or ICU with a non-study ETT already in place Presence of a tracheostomy on ICU admission Unable to be intubated with non-study ETT Declined participation in research or data collection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Endotracheal Tube with Subglottic Secretion Drainage<br>All patients in this arm will be intubated with an ETT with subglottic secretion drainage | Device: Endotracheal tube with subglottic secretion drainage<br>* An endotracheal tube with subglottic secretion drainage<br>|
| Active Comparator: CeraShield Endotracheal Tube<br>All patients in this arm will be intubated with a ceragenin coated ETT | Device: CeraShield Endotracheal Tube<br>* An endotracheal tube coated with with an antimicrobial hydrophilic coating containing ceragenins (CSAs)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Ventilator Associated Pneumonia | The primary outcome will be the occurrence of VAP defined as new, progressive, or persistent radiographic infiltrate on chest radiograph plus any 2 of the following: (1) fever (core temperature >38°C) or hypothermia (temperature <36°C); (2) white blood cell count less than 3.0 × 106/L or exceeding 10 × 106/L, and (3) purulent sputum | Admission to within 48 hours of cessation of invasive mechanical ventilation or 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibiotic Utilization | Antibiotic free days defined as alive and not recieving antibiotics in the 28 day period after intubation | 28 days after intubation | 
| Health care utilization | Duration of mechanical ventilation, duration of ICU stay, duration of hospital stay | 90 days | 
| Health care utilization | Ventilator Free Days defined as alive and off ventilation in the 28 day period after intubation | 28 days | 
| Hospital Mortality | Mortality while hospitalized | 90 days | 
| Airway outcomes | Incidence of post-extubation stridor, lack of endotracheal tube cuff leak | Within 48 hours of extubation | 
| Re-intubation | Rate of re-intubation after extubation from invasive mechanical ventilation | Within 48 hours of extubation | 
| Acceptability of the Intervention | Measured by the Acceptability of Intervention Measure Tool (AIM). AIM is a 5 point scale that measures the perception of implementation stakeholders that a new treatment (in this study new type of ETT) is agreeable or satisfactory. AIM is an ordinal scale that ranges from completely agree to completely disagree. | During the conduct of the trial up to 1 year from study initiation | 
| Feasibility of multi-center cluster randomized trial - 1 | Determination of required sample size for a multi-center study based on the event rates (Occurrence of VAP as in outcome 1 and antibiotic utilization as in outcome 2) in this single center trial. Sample size will be calculated for the multicenter study and feasibility will be informed by the magnitude of the sample size and the potential resources required to conduct such as study including the number of centers. | During the trial up to 1 year from study start | 
| Feasibility of multi-center cluster randomized trial - 2 | Acceptable availability of routinely collected data for analysis of study conduct defined as less than 10% missing data | During the trial up to 1 year from study start |