Cuff Pressure Control and Evacuation of Subglottic Secretions To Prevent Pneumonia

An Innovative Cuff Pressure Control and Evacuation of Subglottic Secretions To Prevent Pneumonia. A Multicenter Cluster-Randomized Trial

Multicenter, cluster randomized, controlled, open-label trial to assess if AnapnoGuard System can minimize tracheal microaspiration and the risk of ventilator-associated pneumonia when compared to standard treatment

Study Overview

• Status: Active, not recruiting
• Conditions: Respiratory Failure
• Intervention / Treatment: Device: Continuous cuff pressure regulation; Device: Automatic subglottic secretion drainage; Diagnostic test: Tracheobronchial colonization assessment; Diagnostic test: Microaspiration assessment; Diagnostic test: VAP assessment; Device: Intermittent cuff pressure regulation; Device: Manual subglottic secretion drainage

Detailed Description

Maintaining the endotracheal tube (ETT) cuff appropriately inflated plays a crucial role in the management of intubated patients because overinflation may cause tracheal wall damage, ulcerations and stenosis, and underinflation may results in fluid leakage and ventilator-associated pneumonia (VAP).

During mechanical ventilation, secretions contaminated with oropharyngeal and gastric pathogens pool in the subglottic space (tracheal region between the ETT cuff and the vocal cords) and enter the lower airways via microaspiration.

Subglottic secretion drainage (SSD) reduces the incidence of VAP and can be performed intermittently or continuously, with varying efficacy and often causing secondary tracheal mucosa lesions.

AnapnoGuard (AG) ETT has three dedicated lines (two suction lines and one sensing/venting/rinsing line) and can be connected to the AG 100 System, a new device which provides high-sensitive capnography of subglottic space and consequent adjustment of cuff pressure, to avoid fluid leakage and overinflation. It also evacuates secretions from the subglottic space by simultaneously rinsing/venting this space using the ETT dedicated line.

The hypothesis is that AG System may reduce the incidence of microaspiration, bacterial tracheal colonization and consequently the risk of VAP when compared to standard treatment (ETT with manually performed secretion drainage and cuff pressure control).

• Study Type: Interventional
• Enrollment (Actual): 270
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gennaro De Pascale, MD; Phone Number: +393208998173; Email: gennaro.depascale@policlinicogemelli.it

Study Locations

• Israel
  • Tel Aviv, Israel
    • Shamir medical center
• Italy
  • Ancona, Italy
    • Azienda ospedaliera universitaria "Ospedali riuniti di Ancona"
  • Bari, Italy
    • Azienda ospedaliera universitaria "Policlinico di Bari"
  • Milano, Italy
    • Humanitas Research Hospital
  • Modena, Italy
    • Azienda ospedaliera universitaria di Modena
  • Napoli, Italy
    • Azienda ospedaliera Federico II
  • Napoli, Italy
    • Azienda ospedaliera universitaria "Luigi Vanvitelli"
  • Palerme, Italy
    • Policlinico "P. Giaccone"
  • Perugia, Italy
    • Azienda ospedaliera Perugia
  • Roma, Italy, 00168
    • Fondazione Policlinico "A. GEMELLI"
  • Torino, Italy
    • Azienda ospedaliera universitaria Città della Salute e della Scienza di Torino - presidio Molinette

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Primary intubation with the study ETT
• Expected duration of mechanical ventilation >48 hours
• Age older than 18 years

Exclusion Criteria:

• Invasive mechanical ventilation in the last 14 days,
• Contraindication for enteral feeding
• Clinical evidence of inhalation before intubation
• Pregnancy
• Enrolling in another study that may interfere with this trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AnapnoGuard group; Patients intubated with AnapnoGuard endotracheal tube (polyvinylchloride tube with ellipsoidal shape, thin wall polyurethane cuff with dual suction lines and an extra venting line) which is connected to AnapnoGuard 100 System	Device: Continuous cuff pressure regulation; Within 24 hours, AnapnoGuard tube will be connected to AnapnoGuard 100 control device. It includes an automatic high-sensitive subglottic capnograph which measures every few minutes the carbon dioxide level in the subglottic space. If the level of carbon dioxide is above the threshold (established by animal studies) the system will increase the cuff pressure by a formula, if the level is below the threshold, the system will decrease the cuff pressure by 1 mmHg. Variations of cuff pressure are allowed only between pressure limits set by the user (minimum and maximum); Device: Automatic subglottic secretion drainage; Within 24 hours, AnapnoGuard tube will be connected to AnapnoGuard 100 device control which provides continuous subglottic secretion drainage (two different suction lines) and venting/rinsing (a third dedicated line); Diagnostic test: Tracheobronchial colonization assessment; Tracheal aspirate will be performed after intubation and after 72 hours for microbiological colture; Diagnostic test: Microaspiration assessment; Tracheal aspirates will be performed 72 hours after intubation, and collected in a predefined study center to measure pepsin and salivary amylase; Diagnostic test: VAP assessment; Patients will be follow to detect clinical, radiological or microbiological signs of VAP. If suspected, a tracheal aspirate or a bronchoalveolar lavage is performed to confirm the diagnosis
Active Comparator: Control group; Patients intubated with TaperGuard Evac endotracheal tube (polyvinylchloride conic cuff with additional lumen for subglottic secretion suctioning)	Diagnostic test: Tracheobronchial colonization assessment; Tracheal aspirate will be performed after intubation and after 72 hours for microbiological colture; Diagnostic test: Microaspiration assessment; Tracheal aspirates will be performed 72 hours after intubation, and collected in a predefined study center to measure pepsin and salivary amylase; Diagnostic test: VAP assessment; Patients will be follow to detect clinical, radiological or microbiological signs of VAP. If suspected, a tracheal aspirate or a bronchoalveolar lavage is performed to confirm the diagnosis; Device: Intermittent cuff pressure regulation; ET cuff pressure will be manually measured three times per day using a portable manometer, and kept constant within 20-30 cmH2O; Device: Manual subglottic secretion drainage; Subglottic secretions will be manually drained with a 10 mL syringe, using the only dedicated lumen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bacterial tracheobronchial colonization (number of events)	The proportion of patients with bacterial tracheobronchial colonization (> 10^3 CFU/mL) on Day 3 after randomization, measured from tracheal aspirate	3 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilator-associated pneumonia (number of events)	The proportion of patients who develop ventilator-associated pneumonia (presence of radiological and clinical signs consisting of a new and persistent infiltrate on the chest radiograph associated with two of the three following criteria: purulent tracheal aspirates, hyperthermia >38 °C or hypothermia <36 °C and peripheral leucocytosis >10,000/μ l or <1,500/μ. A microbiological confirmation is required using tracheal aspirate ≥ 10^5 CFU/ml or bronchoalveolar lavage ≥ 10^4 CFU/ml)	28 days
Microaspiration (number of events)	The prevalence of patients with gastric and oropharyngeal microaspiration or abundant microaspiration (Microaspiration is defined by the presence of alpha-amylase >1685 UI/L in tracheal aspirates. Abundant microaspiration is defined by pepsin level >200 ng/mL in >30 % of tracheal aspirates during the 48 h following inclusion.)	2 days
Ventilator-associated events (number of events)	The proportion of patients who develop ventilator-associated events, defined as a sustained increase in ventilator support (minimum PEP increase >2.5 cm H2 O, or minimum FiO2 increase >15 %) after >2 days of stable or decrease settings	28 days
Time to ventilator-associated pneumonia (days)	The time until the first diagnosis of ventilator-associated pneumonia is established	28 days
Antibiotic-free days (days)	The number of days in which the patient is not treated with any antibiotic drug	28 days
Ventilator-free days (days)	The number of days in which patients do not receive mechanical ventilation within 28 days from randomization	28 days
Length of intensive care unit stay (days)	The number of days in which the patient is admitted in intensive care unit or in hospital	28 days
Length of hospital stay (days)	The number of days in which the patient is admitted in hospital	28 days
In-intensive care unit mortality (number of events)	All-cause mortality, assessed at the discharge from the intensive care unit	28 days
In-hospital mortality (number of events)	All-cause mortality, assessed at the discharge from the hospital	28 days
28-day mortality (number of events)	All-cause 28-day mortality	28 days
60-day mortality (number of events)	All-cause 60-day mortality	60 days
90-day mortality (number of events)	All-cause 90-day mortality	90 days
Tracheobronchial colonization count (number of events)	The proportion of tracheal aspirates with colonization count >10^4, 10^5, 10^6, >= 10^7 CFU/mL	3 days
Post-extubation stridor (number of events)	The proportion of patients who experience stridor after extubation	1 day
Total subglottic secretion volume	The amount of secretions which has been drained from subglottic space during the enrolment	28 days
Daily subglottic secretion volume	Daily amount of secretions which has been drained from subglottic space	1 day
Out of range cuff pressure	The proportion of cuff pressure values whose are out of the safety limits	28 days

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Collaborators: Catholic University of the Sacred Heart
• Investigators: Principal Investigator: Gennaro De Pascale, MD, Fondazione Policlinico A. Gemelli IRCCS; Study Chair: Massimo Antonelli, MD, Fondazione Policlinico A. Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2022
• Primary Completion (Actual): February 20, 2024
• Study Completion (Estimated): June 6, 2024

Study Registration Dates

• First Submitted: May 16, 2022
• First Submitted That Met QC Criteria: May 30, 2022
• First Posted (Actual): June 3, 2022

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Respiratory Insufficiency; Pneumonia
• Other Study ID Numbers: 4739

Drug and device information, study documents

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