Ceragenin Coated Endotracheal Tubes for the Prevention of Ventilator Associated Pneumonia (CEASEVAP)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Ventilator Associated Pneumonia
• Intervention / Treatment: Device: Endotracheal tube with subglottic secretion drainage; Device: CeraShield Endotracheal Tube

Detailed Description

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.

1. 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.
2. 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.

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Kingston, Ontario, Canada, k7l2v7
      • Kingston Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult critically ill patients with respiratory failure requiring intubation

Exclusion Criteria:

1. Admission to hospital or ICU with a non-study ETT already in place
2. Presence of a tracheostomy on ICU admission
3. Unable to be intubated with non-study ETT
4. Declined participation in research or data collection

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Dr. John Muscedere
• Investigators: Principal Investigator: John Muscedere, MD, Queens University

Publications and helpful links

General Publications

• Muscedere J, Rewa O, McKechnie K, Jiang X, Laporta D, Heyland DK. Subglottic secretion drainage for the prevention of ventilator-associated pneumonia: a systematic review and meta-analysis. Crit Care Med. 2011 Aug;39(8):1985-91. doi: 10.1097/CCM.0b013e318218a4d9.
• Safdar N, Dezfulian C, Collard HR, Saint S. Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med. 2005 Oct;33(10):2184-93. doi: 10.1097/01.ccm.0000181731.53912.d9.
• Muscedere JG, Day A, Heyland DK. Mortality, attributable mortality, and clinical events as end points for clinical trials of ventilator-associated pneumonia and hospital-acquired pneumonia. Clin Infect Dis. 2010 Aug 1;51 Suppl 1:S120-5. doi: 10.1086/653060.
• Diaconu O, Siriopol I, Polosanu LI, Grigoras I. Endotracheal Tube Biofilm and its Impact on the Pathogenesis of Ventilator-Associated Pneumonia. J Crit Care Med (Targu Mures). 2018 Apr 1;4(2):50-55. doi: 10.2478/jccm-2018-0011. eCollection 2018 Apr.
• Epand RM, Epand RF, Savage PB. Ceragenins (cationic steroid compounds), a novel class of antimicrobial agents. Drug News Perspect. 2008 Jul-Aug;21(6):307-11. doi: 10.1358/dnp.2008.21.6.1246829.
• Grimshaw J, Campbell M, Eccles M, Steen N. Experimental and quasi-experimental designs for evaluating guideline implementation strategies. Fam Pract. 2000 Feb;17 Suppl 1:S11-6. doi: 10.1093/fampra/17.suppl_1.s11.

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2023
• Primary Completion (Actual): March 28, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: February 23, 2023
• First Submitted That Met QC Criteria: February 27, 2023
• First Posted (Actual): March 9, 2023

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Cross Infection; Iatrogenic Disease; Healthcare-Associated Pneumonia; Pneumonia; Pneumonia, Ventilator-Associated
• Other Study ID Numbers: 6036323

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes