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
Authors: IMPACTO-MR, VATICAN Trial Investigators and BRICNet, Bruno Martins Tomazini, Bruno Adler Maccagnan Pinheiro Besen, Camila Dietrich, Ana Paula Rossi Gandara, Debora Patrícia Silva, Carla Cristina Gomes Pinheiro, Mariane Nascimento Luz, Renata Rodrigues de Mattos, Luiz Fernando Lima Reis, Roberta Muriel Longo Roepke, Carlos Sérgio Luna Gomes Duarte, Antônio Paulo Nassar Júnior, Viviane Cordeiro Veiga, Beatriz Arns, Giovanna Marssola Nascimento, Adriano José Pereira, Alexandre Biasi Cavalcanti, Flávia Ribeiro Machado, Luciano Cesar Pontes Azevedo
Journal: Crit Care Sci (2024)
MeSH terms: Anti-Bacterial Agents / administration & dosage, Anti-Bacterial Agents / therapeutic use, Bronchitis / drug therapy, Bronchitis / microbiology, Pneumonia, Ventilator-Associated / drug therapy, Pneumonia, Ventilator-Associated / microbiology, Respiration, Artificial / adverse effects, Tracheitis / drug therapy, Watchful Waiting, Multicenter Study, Randomized Controlled Trial, Clinical Trial Protocol, Case Reports, Humans, Intensive Care Units, Anti-Bacterial Agents

Background:
Ventilator-associated tracheobronchitis is a common condition among invasively ventilated patients in intensive care units, for which the best treatment strategy is currently unknown. We designed the VATICAN (Ventilator-Associated Tracheobronchitis Initiative to Conduct Antibiotic Evaluation) trial to assess whether a watchful waiting antibiotic treatment strategy is noninferior to routine antibiotic treatment for ventilator-associated tracheobronchitis regarding days free of mechanical ventilation.
Methods:
VATICAN is a randomized, controlled, open-label, multicenter noninferiority trial. Patients with suspected ventilator-associated tracheobronchitis without evidence of ventilator-associated pneumonia or hemodynamic instability due to probable infection will be assigned to either a watchful waiting strategy, without antimicrobial administration for ventilator-associated tracheobronchitis and prescription of antimicrobials only in cases of ventilator-associated pneumonia, sepsis or septic shock, or another infectious diagnosis, or to a routine antimicrobial treatment strategy for seven days. The primary outcome will be mechanical ventilation-free days at 28 days, and a key secondary outcome will be ventilator-associated pneumonia-free survival. Through an intention-to-treat framework with a per-protocol sensitivity analysis, the primary outcome analysis will address noninferiority with a 20% margin, which translates to a 1.5 difference in ventilator-free days. Other analyses will follow a superiority analysis framework.
Conclusion:
The VATICAN trial will follow all national and international ethical standards. We aim to publish the trial in a high-visibility general journal and present it at critical care and infectious disease conferences for dissemination. These results will likely be immediately applicable to the bedside upon trial completion and will provide information with a low risk of bias for guideline development.