Antimicrobial Treatment in Patients With Ventilator-associated Tracheobronchitis

Critical Illness Clinical Trial

— TAVeM2  

Official title:

Antimicrobial Treatment in Patients With Ventilator-associated Tracheobronchitis: a Prospective Randomized Placebo-controlled Double-blind Multicenter Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03012360
• Other study ID #: 2015_66
• Secondary ID: 2016-000735-41
• Status: Recruiting
• Phase: Phase 4
• Start date: February 8, 2018
• Est. completion date: September 2023

Study information

• Verified date: August 2022
• Source: University Hospital, Lille
• Contact: Saad NSEIR, MD,PhD
• Phone: 3 20 44 40 84
• Email: saadalla.nseir[@]chru-lille.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 154
• Est. completion date: September 2023
• Est. primary completion date: September 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness
• Mechanical Ventilation Complication

Intervention

Drug:
• ceftriaxone
2 g iv every 24h
• ciprofloxacin
400 mg iv every 8h
• imipenem
1 g iv every 8h
• linezolid
600 mg iv every 12h
• 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

Locations

Country	Name	City	State
France	Hôpital Roger Salengro, CHRU	Lille

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Lille	Ministry of Health, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The percentage of patients with a transition from VAT to VAP,	VAP is defined using the following criteria: new or progressive pulmonary infiltrate; two of the following criteria: temperature >38°C or <36.5°C leukocyte count >12,000/µL or <4,000/µL purulent endotracheal aspirate; 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	duration of mechanical ventilation-free days		from randomization to day 28 (4 weeks)
Secondary	duration of antibiotic free-days		from randomization to day 28 (4 weeks)
Secondary	length of ICU stay		from randomization to day 28 (4 weeks)
Secondary	mortality		at day 28 and day 90 after randomization
Secondary	percentage of patients with ICU-acquired colonization related to MDR bacteria		from randomization to day 28 (4 weeks)
Secondary	percentage of patients with ventilator-associated events		from randomization to day 28 (4 weeks)
Secondary	percentage of patients with ICU-acquired infection related to MDR bacteria		from randomization to day 28 (4 weeks)