Antimicrobial Treatment in Patients With Ventilator-associated Tracheobronchitis

NCT ID: NCT03012360

Last Updated: 2025-12-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 103 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-08
• Study Completion Date: 2024-07-07

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.

Conditions

Mechanical Ventilation Complication; Critical Illness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

no antibiotic treatment for VAT

3 days of placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

The SSI 0.9% or dextrose 5% used are based on routine procedure in different participating centers.Placebo will be prepared using IV bags, with the same of quantity as IMP

antibiotic treatment for 3 days

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

Group Type: EXPERIMENTAL

ceftriaxone

Intervention Type: DRUG

2 g iv every 24h

ciprofloxacin

Intervention Type: DRUG

400 mg iv every 8h

imipenem

Intervention Type: DRUG

1 g iv every 8h

linezolid

Intervention Type: DRUG

600 mg iv every 12h

placebo

Intervention Type: DRUG

The SSI 0.9% or dextrose 5% used are based on routine procedure in different participating centers.Placebo will be prepared using IV bags, with the same of quantity as IMP

Interventions

ceftriaxone

2 g iv every 24h

Intervention Type: DRUG

ciprofloxacin

400 mg iv every 8h

Intervention Type: DRUG

imipenem

1 g iv every 8h

Intervention Type: DRUG

linezolid

600 mg iv every 12h

Intervention Type: DRUG

placebo

The SSI 0.9% or dextrose 5% used are based on routine procedure in different participating centers.Placebo will be prepared using IV bags, with the same of quantity as IMP

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, France

OTHER_GOV

Sponsor Role: collaborator

University Hospital, Lille

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Saad NSEIR, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Lille

Locations

Hôpital Roger Salengro, CHRU

Lille, , France

Countries

France

Other Identifiers

2016-000735-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2015_66

Identifier Type: -

Identifier Source: org_study_id