Antimicrobial Treatment in Patients With Ventilator-associated Tracheobronchitis

Phase 4TerminatedNCT03012360

University Hospital, Lille103 enrolled

Overview

Antimicrobial treatment could be beneficial in patients with ventilator-associated tracheobronchitis (VAT). The hypothesis of this study is that antibiotic treatment for VAT (3 or 7 days), compared with no antibiotic treatment, would reduce the incidence of transition from VAT to ventilator-associated pneumonia (VAP).

The main objective of this randomized controlled multicenter double-blind trial is to assess the efficiency of two durations (3 or 7 days) of antibiotic treatment for VAT, compared with no antibiotic treatment, in reducing the incidence of transition from VAT to ventilator-associated pneumonia (VAP). Secondary objectives are to determine the impact of two durations (3 or 7 days) of antibiotic treatment for VAT, compared with no antibiotic treatment, on: * duration of mechanical-ventilation free days * duration of antibiotic free days * length of ICU stay * mortality at day 28 and day 90 * incidence of ICU-acquired colonization related to multidrug resistant (MDR) bacteria * incidence of ICU-acquired infection related to MDR bacteria * incidence of ventilator-associated events After informed consent, patients will be randomized (1:1:1) to receive 0 (control group), 3 or 7 days (experimental groups) of antibiotic treatment for VAT Antibiotic treatment is standardized, based on the time of onset of VAT, and presence of risk factors for MDR bacteria: * patients with early-onset VAT with no risk factor for MDR bacteria will receive ceftriaxone (2 g iv every 24h). * patients with late-onset VAT (after day 4 of mechanical ventilation), or with at least one risk factor for MDR bacteria will receive imipenem (1 g iv every 8h), and ciprofloxacin (400 mg iv every 8h) as empirical treatment. When methicillin-resistant Staphylococcus aureus is suspected, linezolid (600 mg iv every 12h) will be added to empirical treatment. Patients randomized in control group will receive 7 days of placebo, and those randomized in the first experimental arm (3 days of antibiotics) will receive 4 days of placebo.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

103

Conditions

Mechanical Ventilation Complication Critical Illness

Interventions

ceftriaxoneDRUG

2 g iv every 24h

ciprofloxacinDRUG

400 mg iv every 8h

imipenemDRUG

1 g iv every 8h

linezolid

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * All adult patients hospitalized in the ICU with a first episode of VAT diagnosed \>48 hours after starting invasive mechanical ventilation are eligible for this study. VAT is defined using the following criteria: 1. absence of new infiltrate on chest X ray 2. two of the three following conditions: fever \> 38.5 °C or \<36.5, leucocyte count \> than 12 000 cells per μL or \<than 4000 cells per μL purulent tracheal secretions 3. and positive tracheal aspirate (≥105 cfu/mL) Exclusion Criteria: * long-term tracheostomy at ICU admission * patients who develop VAP before VAT * patients already receiving antibiotics active against all the microorganisms responsible for VAT * severe immunosuppression * pregnancy or breastfeeding * patients \<18 years * patients already included in another study, with potential interaction with the primary objective of the current study * known resistance to imipenem and ciprofloxacin of bacteria responsible for VAT * treatment limitation decisions * moribund patients (likely to die within 24 h) * allergy to any of study drugs: hypersensitivity to any carbapenem, severe hypersensitivity (for example anaphylactic reaction or severe cutaneous reaction) to any other antibiotic form beta-lactam group (such as penicillin or cephalosporin), severe hypersensitivity (for example anaphylactic reaction) to any other antibiotic from beta-lactam group (penicillin, monobactam or carbapenem), hypersensitivity to quinolones

Locations (1)

Hôpital Roger Salengro, CHRU

Lille, France

Outcomes

Primary Outcomes

The percentage of patients with a transition from VAT to VAP,

VAP is defined using the following criteria: 1. new or progressive pulmonary infiltrate 2. two of the following criteria: temperature \>38°C or \<36.5°C leukocyte count \>12,000/μL or \<4,000/μL purulent endotracheal aspirate 3. positive tracheal aspirate (≥105 cfu/mL) or bronchoalveolar lavage (≥104 cfu/mL). VAP will be considered as subsequent to VAT, when it is diagnosed \>24h after VAT occurrence. Only first episodes of VAP diagnosed \>48h after starting mechanical ventilation will be taken into account.