Clinical trial NCT03012360: Antimicrobial Treatment in Patients With Ventilator-associated Tracheobronchitis
Official title: Antimicrobial Treatment in Patients With Ventilator-associated Tracheobronchitis: a Prospective Randomized Placebo-controlled Double-blind Multicenter Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Mechanical Ventilation Complication
Critical Illness
Keywords: Infectiology
Biology of infectious agents
Hygiene
Pneumology
Critical Care
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2017-01-06
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: The percentage of patients with a transition from VAT to VAP,
timeFrame: from randomization to day 28 (4 weeks)
Secondary outcomes:
measure: duration of mechanical ventilation-free days
timeFrame: from randomization to day 28 (4 weeks)
measure: duration of antibiotic free-days
timeFrame: from randomization to day 28 (4 weeks)
measure: length of ICU stay
timeFrame: from randomization to day 28 (4 weeks)
measure: mortality
timeFrame: at day 28 and day 90 after randomization
measure: percentage of patients with ICU-acquired colonization related to MDR bacteria
timeFrame: from randomization to day 28 (4 weeks)
measure: percentage of patients with ventilator-associated events
timeFrame: from randomization to day 28 (4 weeks)
measure: percentage of patients with ICU-acquired infection related to MDR bacteria
timeFrame: from randomization to day 28 (4 weeks)
Other outcomes:
Locations:
city: Lille
country: France
facility: Hôpital Roger Salengro, CHRU
Study officials:
affiliation: University Hospital, Lille
name: Saad NSEIR, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: