Ventilator-associated Tracheobronchitis Initiative to Conduct Antibiotic Evaluation

Tracheobronchitis Clinical Trial

— VATICAN  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05266066
• Other study ID #: 48749421.0.1001.5461
• Status: Recruiting
• Phase: N/A
• Start date: July 11, 2022
• Est. completion date: December 1, 2026

Study information

• Verified date: January 2024
• Source: Hospital Sirio-Libanes
• Contact: Bruno M Tomazini, MD
• Phone: 5511982839173
• Email: bruno.mtomazini[@]hsl.org.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 590
• Est. completion date: December 1, 2026
• Est. primary completion date: November 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

1. Temperature >38.0°C or <36°C OR leukocytes >12000/mL or <4000/mL or presence >10% of immature forms, AND

2. 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

Related Conditions & MeSH terms

• Tracheobronchitis

Intervention

Other:
• Clinical observation without antibiotic therapy for VAT
Patients will receive standard care plus antibiotic if new organ dysfunction or new infections other than VAT.
• 7 day antibiotic course for VAT
Patients will receive standard care plus 7 day course of antibiotic.

Locations

Country	Name	City	State
Brazil	Hospital Santa Casa de Belo Horizonte	Belo Horizonte	MG
Brazil	Hospital OTOClinica	Fortaleza	CE
Brazil	Hospital Itapetininga	Itapetininga	SP
Brazil	Hospital Unimed Limeira	Limeira	SP
Brazil	Hospital Universitário Regional do Norte do Paraná	Londrina	PR
Brazil	Hospital Municipal de Maringá	Maringá	PR
Brazil	Hospital Vila da Serra	Nova Lima	MG
Brazil	Hospital Tricentenário	Olinda	PE
Brazil	Santa Casa de Misericórdia de Passos	Passos	MG
Brazil	Hospital Ernesto Dornelles	Porto Alegre	RS
Brazil	Hospital Estadual Mario Covas	Santo André	SP
Brazil	Hospital São Joao Del Rei	São João Del Rei	MG
Brazil	Hospital Samaritano	São Paulo	SP
Brazil	Hospital São Paulo	São Paulo	SP
Brazil	Hospital Santa Casa de Sorocaba	Sorocaba	SP
Brazil	Hospital Vila Velha	Vila Velha	ES

Sponsors (7)

Lead Sponsor	Collaborator
Hospital Sirio-Libanes	BP - A Beneficência Portuguesa de São Paulo, Brazilian Research in Intensive Care Network (BRICNet), Hospital Alemão Oswaldo Cruz, Hospital do Coracao, Hospital Israelita Albert Einstein, Hospital Moinhos de Vento

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Nosocomial infections	Incidence of culture positive nosocomial infections in 28 days	28 days after randomization
Other	Adverse events	Severe adverse events	28 days after randomization
Primary	Ventilator free days	Days alive and free from mechanical ventilation	28 days after randomization
Secondary	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
Secondary	Mortality	All cause mortality	28 days after randomization
Secondary	Ventilator associated pneumonia	Ventilator associated pneumonia incidence	14 and 28 days after randomization
Secondary	Intensive care unit free days	Days alive and free from intensive care unit	28 days after randomization
Secondary	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.
Secondary	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
Secondary	Antibiotic free days	Days alive and free from antibiotic	28 days after randomization
Secondary	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