Respiratory Failure
Conditions
Brief summary
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
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).
Interventions
DEVICEContinuous 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)
DEVICEIntermittent 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
DEVICEAutomatic 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)
DEVICEManual subglottic secretion drainage
Subglottic secretions will be manually drained with a 10 mL syringe, using the only dedicated lumen
DIAGNOSTIC_TESTTracheobronchial colonization assessment
Tracheal aspirate will be performed after intubation and after 72 hours for microbiological colture
DIAGNOSTIC_TESTMicroaspiration assessment
Tracheal aspirates will be performed 72 hours after intubation, and collected in a predefined study center to measure pepsin and salivary amylase
DIAGNOSTIC_TESTVAP 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
Sponsors
Catholic University of the Sacred Heart
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Multicenter cluster randomized controlled and open-label trial. Because intubation is an urgent intervention in critically ill patients patients with acute respiratory failure, individual randomization is considered too complex and we predetermined cluster of 9 consecutive patients, stratified by centers, with each cluster being assigned to one of the study groups.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bacterial tracheobronchial colonization (number of events) | 3 days | The proportion of patients with bacterial tracheobronchial colonization (\> 10\^3 CFU/mL) on Day 3 after randomization, measured from tracheal aspirate |
Other
| Measure | Time frame | Description |
|---|---|---|
| Microaspiration (number of events) | 2 days | 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.) |
| Ventilator-associated events (number of events) | 28 days | 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 |
| Time to ventilator-associated pneumonia (days) | 28 days | The time until the first diagnosis of ventilator-associated pneumonia is established |
| Antibiotic-free days (days) | 28 days | The number of days in which the patient is not treated with any antibiotic drug |
| Ventilator-free days (days) | 28 days | The number of days in which patients do not receive mechanical ventilation within 28 days from randomization |
| Length of intensive care unit stay (days) | 28 days | The number of days in which the patient is admitted in intensive care unit or in hospital |
| Length of hospital stay (days) | 28 days | The number of days in which the patient is admitted in hospital |
| In-intensive care unit mortality (number of events) | 28 days | All-cause mortality, assessed at the discharge from the intensive care unit |
| Ventilator-associated pneumonia (number of events) | 28 days | 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-day mortality (number of events) | 28 days | All-cause 28-day mortality |
| 60-day mortality (number of events) | 60 days | All-cause 60-day mortality |
| 90-day mortality (number of events) | 90 days | All-cause 90-day mortality |
| Tracheobronchial colonization count (number of events) | 3 days | The proportion of tracheal aspirates with colonization count \>10\^4, 10\^5, 10\^6, \>= 10\^7 CFU/mL |
| Post-extubation stridor (number of events) | 1 day | The proportion of patients who experience stridor after extubation |
| Total subglottic secretion volume | 28 days | The amount of secretions which has been drained from subglottic space during the enrolment |
| Daily subglottic secretion volume | 1 day | Daily amount of secretions which has been drained from subglottic space |
| Out of range cuff pressure | 28 days | The proportion of cuff pressure values whose are out of the safety limits |
| In-hospital mortality (number of events) | 28 days | All-cause mortality, assessed at the discharge from the hospital |
Countries
Israel, Italy
Outcome results
None listed