Ventilator-associated Tracheobronchitis Initiative to Conduct Antibiotic Evaluation (VATICAN)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Tracheobronchitis; Ventilator Associated Tracheobronchitis
• Intervention / Treatment: Other: Clinical observation without antibiotic therapy for VAT; Other: 7 day antibiotic course for VAT

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 Type: Interventional
• Enrollment (Estimated): 590
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bruno M Tomazini, MD; Phone Number: 5511982839173; Email: bruno.mtomazini@hsl.org.br
• Study Contact Backup: Name: Bruno AMP Besen, MD; Email: brunobesen@yahoo.com.br

Study Locations

• Brazil
  • CE
    • Fortaleza, CE, Brazil
      • Recruiting
      • Hospital Otoclínica
      • Contact: Fabio H Lacerda, MD
  • ES
    • Vila Velha, ES, Brazil
      • Recruiting
      • Hospital Vila Velha
      • Contact: Gedealvares Souza, MD
  • MG
    • Belo Horizonte, MG, Brazil
      • Recruiting
      • Hospital Santa Casa de Belo Horizonte
      • Contact: Claudio Dornas de Oliveira, MD
    • Nova Lima, MG, Brazil
      • Recruiting
      • Hospital Vila da Serra
      • Contact: Hugo Urbano
    • Passos, MG, Brazil
      • Recruiting
      • Santa Casa de Misericordia de Passos
      • Contact: Vanildes Bernardes
    • São João Del Rei, MG, Brazil
      • Recruiting
      • Hospital São Joao Del Rei
      • Contact: Jorge Paranhos, MD
  • PE
    • Olinda, PE, Brazil
      • Recruiting
      • Hospital Tricentenário
      • Contact: Carlos Duarte, MD
  • PR
    • Londrina, PR, Brazil
      • Recruiting
      • Hospital Universitário Regional do Norte do Paraná
      • Contact: Cintia Grion
    • Maringá, PR, Brazil
      • Recruiting
      • Hospital Municipal de Maringá
      • Contact: Francielle Pereira, MD
  • RS
    • Porto Alegre, RS, Brazil
      • Recruiting
      • Hospital Ernesto Dornelles
      • Contact: Carla Rynkowski, MD
  • SP
    • Itapetininga, SP, Brazil
      • Recruiting
      • Hospital Itapetininga
      • Contact: Vivian Irineu, MD
    • Limeira, SP, Brazil
      • Recruiting
      • Hospital Unimed Limeira
      • Contact: Luis Paciencia, MD
    • Santo André, SP, Brazil
      • Recruiting
      • Hospital Estadual Mario Covas
      • Contact: Caio Dernandes, MD
    • Sorocaba, SP, Brazil
      • Recruiting
      • Hospital Santa Casa de Sorocaba
      • Contact: Vivian Leoneza, MD
    • São Paulo, SP, Brazil
      • Recruiting
      • Hospital Samaritano
      • Contact: Livia Melro, MD
    • São Paulo, SP, Brazil
      • Recruiting
      • Hospital Sao Paulo
      • Contact: Flávia R Machado, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nosocomial infections	Incidence of culture positive nosocomial infections in 28 days	28 days after randomization
Adverse events	Severe adverse events	28 days after randomization

Collaborators and Investigators

• Sponsor: Hospital Sirio-Libanes
• Collaborators: Hospital Israelita Albert Einstein; Hospital Moinhos de Vento; Hospital do Coracao; Hospital Alemão Oswaldo Cruz; BP - A Beneficência Portuguesa de São Paulo; Brazilian Research in Intensive Care Network (BRICNet)
• Investigators: Principal Investigator: Bruno M Tomazini, MD, Hospital Sirio-Libanes

Publications and helpful links

General Publications

• IMPACTO-MR, VATICAN Trial Investigators and BRICNet; Tomazini BM, Besen BAMP, Dietrich C, Gandara APR, Silva DP, Pinheiro CCG, Luz MN, Mattos RR, Reis LFL, Roepke RML, Duarte CSLG, Nassar Junior AP, Veiga VC, Arns B, Nascimento GM, Pereira AJ, Cavalcanti AB, Machado FR, Azevedo LCP. VATICAN (Ventilator-Associated Tracheobronchitis Initiative to Conduct Antibiotic Evaluation): protocol for a multicenter randomized open-label trial of watchful waiting versus antimicrobial therapy for ventilator-associated tracheobronchitis. Crit Care Sci. 2024 Aug 26;36:e20240029en. doi: 10.62675/2965-2774.20240029-en. eCollection 2024.
• Tomazini BM, Nassar AP Jr, Lisboa TC, Azevedo LCP, Veiga VC, Catarino DGM, Fogazzi DV, Arns B, Piastrelli FT, Dietrich C, Negrelli KL, Jesuino IA, Reis LFL, Mattos RR, Pinheiro CCG, Luz MN, Spadoni CCDS, Moro EE, Bueno FR, Sampaio CSJC, Silva DP, Baldassare FP, Silva ACA, Veiga T, Barbante L, Lambauer M, Campos VB, Santos E, Santos RHN, Laranjeiras LN, Valeis N, Santucci E, Miranda TA, Patrocinio ACLD, Carvalho A, Sousa EMC, Sousa AHF, Malheiro DT, Bezerra IL, Rodrigues MB, Malicia JC, Silva SSD, Gimenes BDP, Sesin GP, Zavascki AP, Sganzerla D, Medeiros GS, Santos RDRMD, Silva FKR, Cheno MY, Abrahao CF, Oliveira Junior HA, Rocha LL, Nunes Neto PA, Pereira VC, Paciencia LEM, Bueno ES, Caser EB, Ribeiro LZ, Fernandes CCF, Garcia JM, Silva VFF, Santos AJD, Machado FR, Souza MA, Ferronato BR, Urbano HCA, Moreira DCA, Souza-Dantas VC, Duarte DM, Coelho J, Figueiredo RC, Foreque F, Romano TG, Cubos D, Spirale VM, Nogueira RS, Maia IS, Zandonai CL, Lovato WJ, Cerantola RB, Toledo TGP, Tomba PO, Almeida JR, Sanches LC, Pierini L, Cunha M, Sousa MT, Azevedo B, Dal-Pizzol F, Damasio DC, Bainy MP, Beduhn DAV, Jatoba JDVN, Moura MTF, Rego LRM, Silva AVD, Oliveira LP, Sodre Filho ES, Santos SSD, Neves IL, Leao VCA, Paes JLL, Silva MCM, Oliveira CD, Santiago RCB, Paranhos JLDR, Wiermann IGDS, Pedroso DFF, Sawada PY, Prestes RM, Nascimento GC, Grion CMC, Carrilho CMDM, Dantas RLAM, Silva EP, Silva ACD, Oliveira SMB, Golin NA, Tregnago R, Lima VP, Silva KGND, Boschi E, Buffon V, Machado AS, Capeletti L, Foernges RB, Carvalho AS, Oliveira Junior LC, Oliveira DC, Silva EM, Ribeiro J, Pereira FC, Salgado FB, Deutschendorf C, Silva CFD, Gobatto ALN, Oliveira CB, Dracoulakis MDA, Alvaia NOS, Souza RM, Araujo LLC, Melo RMV, Passos LCS, Vidal CFL, Rodrigues FLA, Kurtz P, Shinotsuka CR, Tavares MB, Santana IDV, Gavinho LMDS, Nascimento AB, Pereira AJ, Cavalcanti AB. IMPACTO-MR: a Brazilian nationwide platform study to assess infections and multidrug resistance in intensive care units. Rev Bras Ter Intensiva. 2022 Oct-Dec;34(4):418-425. doi: 10.5935/0103-507X.20220209-pt. Epub 2023 Mar 3.

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2022
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: February 15, 2022
• First Submitted That Met QC Criteria: March 2, 2022
• First Posted (Actual): March 4, 2022

Study Record Updates

• Last Update Posted (Actual): June 19, 2025
• Last Update Submitted That Met QC Criteria: June 16, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Antibiotics; Mechanical ventilation; Critically ill; Ventilator associated Tracheobronchitis
• Additional Relevant MeSH Terms: Anti-Infective Agents; Antitubercular Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular
• Other Study ID Numbers: 48749421.0.1001.5461

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual patient data (IPD) might be shared upon request and approval by the study committee after the study completion.
• IPD Sharing Time Frame: One year after study completion.
• IPD Sharing Access Criteria: Individual patient data might be shared upon request and approval by the study committee after the study completion.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

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