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

• ClinicalTrials.gov Identifier: NCT03012360
• Recruitment Status: Recruiting
• First Posted: January 6, 2017
• Last Update Posted: August 17, 2022
• Sponsor: University Hospital, Lille
• Collaborator: Ministry of Health, France
• Information provided by (Responsible Party): University Hospital, Lille

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Mechanical Ventilation Complication; Critical Illness	Drug: ceftriaxone; Drug: ciprofloxacin; Drug: imipenem; Drug: linezolid; Drug: placebo	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 154 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Antimicrobial Treatment in Patients With Ventilator-associated Tracheobronchitis: a Prospective Randomized Placebo-controlled Double-blind Multicenter Trial
• Actual Study Start Date: February 8, 2018
• Estimated Primary Completion Date: September 2023
• Estimated Study Completion Date: September 2023

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: no antibiotic treatment for VAT; 3 days of placebo	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
Experimental: 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	Drug: ceftriaxone; 2 g iv every 24h; Drug: ciprofloxacin; 400 mg iv every 8h; Drug: imipenem; 1 g iv every 8h; Drug: linezolid; 600 mg iv every 12h; 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

Outcome Measures

Primary Outcome Measures :

1. The percentage of patients with a transition from VAT to VAP, [ Time Frame: from randomization to day 28 (4 weeks) ]

   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.

Secondary Outcome Measures :

1. duration of mechanical ventilation-free days [ Time Frame: from randomization to day 28 (4 weeks) ]
2. duration of antibiotic free-days [ Time Frame: from randomization to day 28 (4 weeks) ]
3. length of ICU stay [ Time Frame: from randomization to day 28 (4 weeks) ]
4. mortality [ Time Frame: at day 28 and day 90 after randomization ]
5. percentage of patients with ICU-acquired colonization related to MDR bacteria [ Time Frame: from randomization to day 28 (4 weeks) ]
6. percentage of patients with ventilator-associated events [ Time Frame: from randomization to day 28 (4 weeks) ]
7. percentage of patients with ICU-acquired infection related to MDR bacteria [ Time Frame: from randomization to day 28 (4 weeks) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Saad NSEIR, MD,PhD; 3 20 44 40 84 ext +33; saadalla.nseir@chru-lille.fr

Locations

France

Hôpital Roger Salengro, CHRU; Recruiting

Lille, France

Principal Investigator: Saad NSEIR, MD,PhD

Sponsors and Collaborators

University Hospital, Lille

Ministry of Health, France

Investigators

• Principal Investigator: Saad NSEIR, MD, PhD; University Hospital, Lille

More Information

• Responsible Party: University Hospital, Lille
• ClinicalTrials.gov Identifier: NCT03012360
• Other Study ID Numbers: 2015_66; 2016-000735-41 ( EudraCT Number )
• First Posted: January 6, 2017
• Last Update Posted: August 17, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Lille:

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

Additional relevant MeSH terms:

Critical Illness; Disease Attributes; Pathologic Processes; Ciprofloxacin; Ceftriaxone; Linezolid; Imipenem; Anti-Bacterial Agents; Anti-Infective Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Cytochrome P-450 CYP1A2 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors