Ceragenin Coated Endotracheal Tubes for the Prevention of Ventilator Associated Pneumonia

Ventilator Associated Pneumonia Clinical Trial

— CEASEVAP  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05761613
• Other study ID #: 6036323
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 21, 2023
• Est. completion date: December 1, 2024

Study information

• Verified date: April 2024
• Source: Queen's University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 400
• Est. completion date: December 1, 2024
• Est. primary completion date: March 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Ventilator-Associated
• Ventilator Associated Pneumonia

Intervention

Device:
• CeraShield Endotracheal Tube
An endotracheal tube coated with with an antimicrobial hydrophilic coating containing ceragenins (CSAs)
• Endotracheal tube with subglottic secretion drainage
An endotracheal tube with subglottic secretion drainage

Locations

Country	Name	City	State
Canada	Kingston Health Sciences Center	Kingston	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Dr. John Muscedere

Country where clinical trial is conducted

Canada, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Antibiotic Utilization	Antibiotic free days defined as alive and not recieving antibiotics in the 28 day period after intubation	28 days after intubation
Secondary	Health care utilization	Duration of mechanical ventilation, duration of ICU stay, duration of hospital stay	90 days
Secondary	Health care utilization	Ventilator Free Days defined as alive and off ventilation in the 28 day period after intubation	28 days
Secondary	Hospital Mortality	Mortality while hospitalized	90 days
Secondary	Airway outcomes	Incidence of post-extubation stridor, lack of endotracheal tube cuff leak	Within 48 hours of extubation
Secondary	Re-intubation	Rate of re-intubation after extubation from invasive mechanical ventilation	Within 48 hours of extubation
Secondary	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
Secondary	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
Secondary	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