Antimicrobial Treatment in Patients With Ventilator-associated Tracheobronchitis

NCT03012360 | Terminated Phase 4

• 2 other identifiers: 2015_662016-000735-41
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

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).

Conditions

Mechanical Ventilation Complication; Critical Illness

Keywords

Infectiology; Biology of infectious agents; Hygiene; Pneumology; Critical Care

Outcome Measures

Primary Outcomes (1)

• 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.

  from randomization to day 28 (4 weeks)

Secondary Outcomes (7)

• duration of mechanical ventilation-free days

  from randomization to day 28 (4 weeks)

• duration of antibiotic free-days

  from randomization to day 28 (4 weeks)

• length of ICU stay

  from randomization to day 28 (4 weeks)

• mortality

  at day 28 and day 90 after randomization

• percentage of patients with ICU-acquired colonization related to MDR bacteria

  from randomization to day 28 (4 weeks)

Study Arms (2)

no antibiotic treatment for VAT

PLACEBO COMPARATOR

3 days of placebo

Drug: placebo

antibiotic treatment for 3 days

EXPERIMENTAL

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

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

Interventions

ceftriaxone DRUG

2 g iv every 24h

antibiotic treatment for 3 days

ciprofloxacin DRUG

400 mg iv every 8h

antibiotic treatment for 3 days

imipenem DRUG

1 g iv every 8h

antibiotic treatment for 3 days

linezolid DRUG

600 mg iv every 12h

antibiotic treatment for 3 days

placebo 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; no antibiotic treatment for VAT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• absence of new infiltrate on chest X ray
• 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
• and positive tracheal aspirate (≥105 cfu/mL)

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Lille: lead
• Ministry of Health, France: collaborator

Study Sites (1)

Hôpital Roger Salengro, CHRU

Lille, France

Location

MeSH Terms

Conditions

Critical Illness

Interventions

Ceftriaxone; Ciprofloxacin; Imipenem; Linezolid

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Thienamycins; Carbapenems; Acetamides; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Saad NSEIR, MD, PhD

  University Hospital, Lille

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2016
• First Posted: January 6, 2017
• Study Start: February 8, 2018
• Primary Completion: July 7, 2024
• Study Completion: July 7, 2024
• Last Updated: December 11, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)