Ventilator-associated Tracheobronchitis Initiative to Conduct Antibiotic Evaluation

Study Overview
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Brief Summary
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The Ventilator Associated tracheobronchitis Initiative to Conduct Antibiotic evaluation (VATICAN) trial is a national, multicenter, non-inferiority trial in ICU patients comparing antibiotic treatment for 7 days versus clinical observation without antibiotic treatment for patients with ventilator-associated tracheobronchitis.

Detailed Description
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There is no consensus on the need for antibiotic treatment for ventilator-associated tracheobronchitis (VAT). There's a lack of high-quality clinical data on this subject, and although some observational studies recommend antibiotic treatment for VAT, some guidelines do not. The VATICAN is a prospective, randomized, single-blinded (analysis), non-inferiority trial evaluating antibiotic treatment for patients with ventilator-associated tracheobronchitis. Patients with clinically diagnosed tracheobronchitis will be randomized to receive antibiotics for 7 days versus clinical observation without antibiotic treatment for VAT. The primary hypothesis is that clinical observation without antibiotic treatment is noninferior to 7-day antibiotic course.

Official Title
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Multicenter Randomized Clinical Trial of Antimicrobial Treatment in Ventilator-associated Tracheobronchitis

Conditions
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Ventilator Associated Tracheobronchitis, Tracheobronchitis

Intervention / Treatment
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* Other: Clinical observation without antibiotic therapy for VAT
* Other: 7 day antibiotic course for VAT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admission to one of the participating ICUs Invasive Mechanical ventilation ≥ 48 hours Available chest imaging of screening day Clinical diagnosis of VAT, defined by the presence of: Temperature >38.0°C or <36°C OR leukocytes >12000/mL or <4000/mL or presence >10% of immature forms, AND Onset of purulent tracheal secretion, or change in characteristics of the secretion, or increase in the amount of respiratory secretion, or increased need for aspiration Culture of tracheal secretion from the day of screening under analysis or collected for analysis Exclusion Criteria: Pregnant or lactating women Indication of use of antibiotics or use of systemic antibiotics for any indications at the time of screening Hemodynamic instability, defined as hypotension unresponsive to volume expansion or increase in vasopressor dose > 0.1mcg/kg/min of noradrenaline or equivalent in the past 6 hours Worsening of gas exchange, defined as an increase in the fraction of inspired oxygen ≥ 20% or an increase in positive end-expiratory pressure (PEEP) ≥ 3 cm of water after a stability period ≥ 2 days Prolonged mechanical ventilation, defined by use of invasive mechanical ventilation for 21 days or more Presence of pulmonary radiological image suggestive of new infectious infiltrate Previous lung disease that makes radiological interpretation for the diagnosis of VAP difficult Previous diagnosis of ventilator associates pneumonia (VAP) during hospitalization Neutropenic patients (neutrophils <1000/mL) Known severe immunosuppression Tracheostomized patients at the time of screening Inclusion in the study in the past 30 days Expected limitation of care or early withdrawal of supportive therapies (< 7 days) Patients with a survival expectancy of less than 48 hours Refusal of consent to participate in the study

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized 1:1 to Clinical observation without antibiotic therapy for VAT vs. 7 day antibiotic course.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clinical observation without antibiotic therapy for VAT<br>Patients will receive standard care and no antibiotic therapy for VAT. Antibiotics will be prescribed if other infections and/or organ dysfunction ensues (especially shock) or there is progression to pneumonia | Other: Clinical observation without antibiotic therapy for VAT<br>* Patients will receive standard care plus antibiotic if new organ dysfunction or new infections other than VAT.<br>|
| Active Comparator: 7 day antibiotic course for VAT<br>Patients will receive standard care and 7 day course of antibiotic therapy for VAT. | Other: 7 day antibiotic course for VAT<br>* Patients will receive standard care plus 7 day course of antibiotic.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilator free days | Days alive and free from mechanical ventilation | 28 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilator associated pneumonia-free survival (Key secondary outcome) | The time between randomization and the diagnostic event of ventilator associated pneumonia or death | 28 days after randomization | 
| Mortality | All cause mortality | 28 days after randomization | 
| Ventilator associated pneumonia | Ventilator associated pneumonia incidence | 14 and 28 days after randomization | 
| Intensive care unit free days | Days alive and free from intensive care unit | 28 days after randomization | 
| Organ dysfunction | Variation in organ dysfunction (measured by the Sequential Organ Failure Assessment Score). Sequential Organ Failure Assessment scores are measured in 6 organ systems (cardiovascular, hematologic, gastrointestinal, renal, pulmonary and neurologic), with each organ scored from 0 to 4, resulting in an aggregated score that ranges from 0 to 24, with higher scores indicating greater dysfunction. | Between randomization and day 7. | 
| Microbiological isolation of multi-resistant bacteria | Microbiological isolation of multi-resistant bacteria. Any isolation of by microbiological cultures of multi-resistant bacteria following the definition: Acinetobacter baumannii: Resistant to carbapenems and/or polymyxins Pseudomonas aeruginosa: Resistant to carbapenems and/or polymyxins Enterobacteriaceae: Resistant to carbapenems and/or polymyxins (in enterobacteria naturally sensitive to polymyxins) Vancomycin-resistant Enterococcus faecium (VRE) Methicillin/Oxacillin Resistant Staphylococcus aureus (MRSA) Methicillin/Oxacillin-Resistant Coagulase Negative Staphylococcus (MRSA) | 28 days after randomization | 
| Antibiotic free days | Days alive and free from antibiotic | 28 days after randomization | 
| Cost analysis | Cost effectiveness analysis. Direct and indirect hospital costs will be measured and used in the analyses. For that, a local costing system will be built, using the absorption costing methodology (top-down). | For the first 28 days after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibiotics, Ventilator associated Tracheobronchitis, Mechanical ventilation, Critically ill