VATICAN: Ventilator-associated Tracheobronchitis Initiative to Conduct Antibiotic Evaluation

Sponsor

Hospital Sirio-Libanes (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05266066

Collaborator

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

590

Enrollment

Locations

Arms

Anticipated Duration (Months)

36.9

Patients Per Site

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Ventilator Associated Tracheobronchitis Tracheobronchitis	Other: Clinical observation without antibiotic therapy for VAT Other: 7 day antibiotic course for VAT	N/A

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

590 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients will be randomized 1:1 to Clinical observation without antibiotic therapy for VAT vs. 7 day antibiotic course.Patients will be randomized 1:1 to Clinical observation without antibiotic therapy for VAT vs. 7 day antibiotic course.

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Mar 1, 2022

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Clinical observation without antibiotic therapy for VAT 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 Patients will receive standard care plus antibiotic if new organ dysfunction or new infections other than VAT.
Active Comparator: 7 day antibiotic course for VAT Patients will receive standard care and 7 day course of antibiotic therapy for VAT.	Other: 7 day antibiotic course for VAT Patients will receive standard care plus 7 day course of antibiotic.

Arm

Intervention/Treatment

Experimental: Clinical observation without antibiotic therapy for VAT

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

Patients will receive standard care plus antibiotic if new organ dysfunction or new infections other than VAT.

Active Comparator: 7 day antibiotic course for VAT

Patients will receive standard care and 7 day course of antibiotic therapy for VAT.

Other: 7 day antibiotic course for VAT

Patients will receive standard care plus 7 day course of antibiotic.

Outcome Measures

Primary Outcome Measures

Ventilator free days [28 days after randomization]
Days alive and free from mechanical ventilation

Secondary Outcome Measures

Mortality [28 days after randomization]
All cause mortality
Ventilator associated pneumonia [14 and 28 days after randomization]
Ventilator associated pneumonia incidence
Intensive care unit free days [28 days after randomization]
Days alive and free from intensive care unit
Organ dysfunction [Between randomization and day 7.]
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.
Microbiological isolation of multi-resistant bacteria [28 days after randomization.]
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)
Antibiotic free days [28 days after randomization]
Days alive and free from antibiotic
Cost analysis [For the first 28 days after randomization]
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).

Other Outcome Measures

Nosocomial infections [28 days after randomization]
Incidence of culture positive nosocomial infections in 28 days
Adverse events [28 days after randomization]
Severe adverse events

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country
1	Hospital OTOClinica	Fortaleza	CE	Brazil
2	Hospital Vila Velha	Vila Velha	ES	Brazil
3	Hospital Santa Casa de Belo Horizonte	Belo Horizonte	MG	Brazil
4	Hospital Vila da Serra	Nova Lima	MG	Brazil
5	Santa Casa de Misericórdia de Passos	Passos	MG	Brazil
6	Hospital São Joao Del Rei	São João Del Rei	MG	Brazil
7	Hospital Tricentenário	Olinda	PE	Brazil
8	Hospital Universitário Regional do Norte do Paraná	Londrina	PR	Brazil
9	Hospital Municipal de Maringá	Maringá	PR	Brazil
10	Hospital Ernesto Dornelles	Porto Alegre	RS	Brazil
11	Hospital Itapetininga	Itapetininga	SP	Brazil
12	Hospital Unimed Limeira	Limeira	SP	Brazil
13	Hospital Estadual Mario Covas	Santo André	SP	Brazil
14	Hospital Santa Casa de Sorocaba	Sorocaba	SP	Brazil
15	Hospital Samaritano	São Paulo	SP	Brazil
16	Hospital São Paulo	São Paulo	SP	Brazil