Antimicrobial Treatment in Patients With Ventilator-associated Tracheobronchitis (TAVeM2)

University Hospital, Lille

Status and phase: Terminated; Phase 4

Conditions: Mechanical Ventilation Complication; Critical Illness

Treatments: Drug: linezolid; Drug: placebo; Drug: ciprofloxacin; Drug: imipenem; Drug: ceftriaxone

Study type: Interventional

Funder types: Other

Identifiers

NCT03012360

2016-000735-41 (EudraCT Number)

2015_66

Details and patient eligibility

About

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).

Full 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.

Enrollment: 103 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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103 participants in 2 patient groups, including a placebo group

no antibiotic treatment for VAT

Placebo Comparator group

Description:

3 days of placebo

Treatment:

Drug: placebo

antibiotic treatment for 3 days

Experimental group

Description:

Patients randomized in one of the two experimental groups will receive 3 days of antimicrobials. 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 (\< 5 days of mechanical ventilation), with no risk factor for MDR will receive ceftriaxone . * patients with late-onset VAT (≥5 days of mechanical ventilation), or with at least one risk factor for multidrug resistant bacteria will receive imipenem , and ciprofloxacin as empirical treatment. When methicillin-resistant Staphylococcus aureus (MRSA) is suspected linezolid will be added to empirical treatment. 3 days of imipenem and ciprofloxacin with optional linezolid, followed by 4 d of placebo

Treatment:

Drug: imipenem

Drug: ceftriaxone

Drug: ciprofloxacin

Drug: placebo

Drug: linezolid