Immediate Versus Substantiated Antibiotic Therapy in Suspected Non-Severe Ventilator-Associated Pneumonia

NCT06743529 | Recruiting

• 1 other identifier: RC24_0466
• Study Type: interventional
• Target: 686
• Locations: 2 countries
• Sites: 41

Brief Summary

Ventilator-associated pneumonia is the leading nosocomial infection in the intensive care units, and is associated with prolonged mechanical ventilation and overuse of antibiotics. Initiating antibiotic therapy immediately after bacteriological sampling (immediate strategy) may expose uninfected patients to unnecessary treatment, while waiting for bacteriological confirmation (conservative strategy) may delay ventilator-associated pneumonia in infected patients. The decision to start antibiotic therapy for ventilator-associated pneumonia takes three points into account: diagnostic probability, the risks to the patient if Antibiotic Therapy is delayed, and the risk of selection of resistant bacteria. Diagnostic probability is limited, given the subjective and non-specific nature of the diagnostic criteria, and only 30-50% of suspected cases are confirmed bacteriologically (whereas samples are only taken when the pre-test probability is sufficient). The risks associated with delayed antibiotic therapy are unknown, as few observational studies have directly assessed the impact of the timing of Antibiotic Therapy initiation on outcome (frequent confusion between delayed and inappropriate Antibiotic Therapy). Iregui et al. found that delaying Antibiotic Therapy by more than 24 hours was associated with higher mortality. However, more recent before-and-after studies have shown that the conservative strategy was associated with lower mortality, more frequently appropriate initial Antibiotic Therapy and shorter duration of Antibiotic Therapy. Similarly, in a recent before-and-after study by our team, initiating antibiotic therapy only upon microbiological confirmation of ventilator-associated pneumonia without septic shock or severe acute respiratory distress syndrome was not associated with an increase in ventilation time, length of stay or excess mortality at D28; but was associated with antibiotic therapy that was more often appropriate (DELAVAP, MARTIN et al, Annals of Intensive Care, 2024). Finally, the recent multicenter TARPP pilot study in surgical intensive care suggests that antibiotic therapy initiated on the basis of microbiological data in patients with suspected ventilator-associated pneumonia not requiring vasopressor support is not associated with a poorer outcome than immediate antibiotic therapy without documentation (the only randomized study on this subject). Antibiotic Therapy for suspected ventilator-associated pneumonia that is not subsequently confirmed is an unnecessary use of antibiotics and carries a risk of selection of resistant bacteria, with adverse effects on public health. It has been reported that a conservative Antibiotic Therapy prescription strategy for intensive care units -acquired infections reduces Antibiotic Therapy use and the incidence of acquired β-lactamase-producing Enterobacteriaceae infections. Overall, in patients with suspected ventilator-associated pneumonia but no signs of clinical severity, given the uncertainty about attributable mortality and concerns about bacterial resistance, the evaluation of the conservative Antibiotic Therapy strategy is reasonable. Some French intensive care units already delay Antibiotic Therapy until confirmation of ventilator-associated pneumonia, except in patients with severe hypoxemia or the need for vasopressor support.

Conditions

Ventilator-Associated Pneumonia (VAP)

Keywords

Intensive care medicine; Intensive care; Ventilator-associated pneumonia; antibiotic sparing

Outcome Measures

Primary Outcomes (1)

• Proportion of patients who die whithin 28 days or are still on invasive mechanical ventilation on day 28

  To assess, in intensive care units patients with suspected nonsevere ventilator-associated pneumonia (no septic shock or severe acute respiratory distress syndrome), whether delaying antibiotic therapy until ventilator-associated pneumonia is confirmed by a positive respiratory-sample culture and/or polymerase chain reaction test (conservative strategy) neither increases day-28 mortality nor prolongs invasive mechanical ventilation , compared to antibiotic therapy initiation immediately after sampling (immediate strategy).

  From day 0 to day 28

Secondary Outcomes (31)

• Sequential Organ Failure Assessment (SOFA) score

  From day 0 to day 7

• Modified clinical pulmonary infection score (mCPIS)

  From day 0 to day 7

• Clinical cure

  day 7

• Invasive mechanical ventilation duration

  From day 0 to day 28

• Ventilator free days

  From day 0 to day 28

Other Outcomes (4)

• Cost-utility analysis (CUA)

  day 90

• EQ-5D-5L EuroQol score

  day 0

• EQ-5D-5L EuroQol score

  day 28

Study Arms (2)

Immediate strategy

ACTIVE COMPARATOR

Usual Care

Procedure: control group

Conservative strategy

EXPERIMENTAL

Conservative strategy

Procedure: Conservative strategy

Interventions

control group PROCEDURE

immediate empiric Antibiotic Therapy (started within 1 hour after randomization) with antibiotic(s) chosen by the bedside physician based on time of ventilator-associated pneumoniaoccurrence, risk of antimicrobial resistance, local ecology, and local protocol. If the respiratory samples are negative, Antibiotic Therapy will be stopped. If ventilator-associated pneumonia is confirmed by positive samples, Antibiotic Therapy active against the recovered bacterial specie(s) will be given for a total of 7 days.

Immediate strategy

Conservative strategy PROCEDURE

No Antibiotic Therapy until receipt of the respiratory sample culture and/or polymerase chain reaction results. If these results are negative, no Antibiotic Therapy is given. If they are positive (confirmed ventilator-associated pneumonia), Antibiotic Therapy is started as appropriate for the bacterial specie(s) detected by culture and/or polymerase chain reaction, without considering gram-stain results and without waiting for antimicrobial susceptibility testing results, and continued for a total of 7 days of Antibiotic Therapy active against the identified bacterial specie(s).

Conservative strategy

Eligibility Criteria

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

You may qualify if:

• Invasive mechanical ventilation for longer than 48 hours
• Respiratory sample collection taken less than two hours ago (at physician discretion, according to local protocol) for a first episode of suspected ventilator-associated pneumonia (meeting the following prespecified criteria) :
• new or changing chest X-ray infiltrates
• plus at least two of the following:
• body temperature ≥38.3°C or ≤35.5°C,
• blood leukocyte count \>12 000/µL or \<4000/µL,
• purulent tracheobronchial aspirate.
• Age ≥18 years
• Informed consent from the patient or next of kin to participation in the trial, or emergency procedure if no next of kin is available
• Patients affiliated to a social security system
• Criteria for severe ventilator-associated pneumonia defined as:
• Vasopressor therapy for onset of septic shock around the time of ventilator-associated pneumonia suspicion
• Onset or severe worsening of hypoxemia (PaO2/FiO2\<150 with 60% FiO2 and 10 mm H2O peak expiratory pressure, or patient on veno-venous extracorporeal membrane oxygenation)
• Immunosuppression defined as :
• leukocytes \<1G/L or neutrophils \<0,5 G/L

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (41)

CHU Angers

Angers, France, 49000, France

RECRUITING

CH Angoulème

Angoulème, France, 16000, France

RECRUITING

CH Argenteuil

Argenteuil, France, 95100, France

RECRUITING

CHU Nantes

Nantes, France, 44000, France

RECRUITING

CH d'Arles

Arles, 13637, France

RECRUITING

CH Avignon

Avignon, 84000, France

RECRUITING

Hôpital Nord Franche Comté

Belfort, 90000, France

RECRUITING

CHU de Bordeaux

Bordeaux, 33076, France

RECRUITING

CHU de Bordeaux

Bordeaux, France

RECRUITING

CH Simone Veil

Cannes, 06414, France

RECRUITING

CH Public du Cotentin

Cherbourg, 50102, France

RECRUITING

CH Cholet

Cholet, 49325, France

RECRUITING

CHU Clermont-Ferrand

Clermont-Ferrand, 63003, France

RECRUITING

CH Dax

Dax, 40107, France

RECRUITING

CHU Dijon

Dijon, 21033, France

RECRUITING

APHP - Hôpital Raymond Poincaré

Garches, 92380, France

RECRUITING

CHD Vendée

La Roche-sur-Yon, 85025, France

RECRUITING

CH Versailles

Le Chesnay, 78157, France

RECRUITING

CH Le Mans

Le Mans, 72000, France

RECRUITING

CH Emile Roux

Le Puy-en-Velay, 43000, France

RECRUITING

CHRU Lille

Lille, 59037, France

RECRUITING

GHB Sud- Hôpital de Lorient

Lorient, 56100, France

RECRUITING

CHU de Lyon - Hôpital Edouard Herriot

Lyon, 69437, France

RECRUITING

CH de Melun

Melun, 77000, France

RECRUITING

CH de Mont de Marsan

Mont-de-Marsan, 40000, France

RECRUITING

CHU Nice -Hôpital Pasteur

Nice, 06100, France

RECRUITING

CHU Nice - Hôpital de l'Archet

Nice, 06200, France

RECRUITING

CHR d'Orléans

Orléans, 45100, France

RECRUITING

APHP - Hôpital Cochin

Paris, 75014, France

RECRUITING

APHP - Hôpital Tenon

Paris, 75020, France

RECRUITING

CH de Pau

Pau, 64000, France

RECRUITING

CHU Rennes

Rennes, 35033, France

RECRUITING

CH de Saint-Nazaire

Saint-Nazaire, 44600, France

RECRUITING

CH de Saint-Malo

St-Malo, 35403, France

RECRUITING

CHRU de Strasbourg - Nouvel Hôpital Civil

Strasbourg, 67091, France

RECRUITING

CHRU de Strasbourg -Hôpital de Hautepierre

Strasbourg, 67098, France

RECRUITING

Hôpital Foch

Suresnes, 92150, France

RECRUITING

CHRU De Tours

Tours, 37044, France

RECRUITING

CH de Valenciennes

Valenciennes, 59300, France

RECRUITING

CH Bretagne Atlantique

Vannes, 56017, France

RECRUITING

CHU La Guadeloupe

Pointe-à-Pitre, 97159, Guadeloupe

RECRUITING

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated

Interventions

Control Groups

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Central Study Contacts

Maëlle MARTIN

CONTACT

0240 087 365; maelle.martin@chu-nantes.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2024
• First Posted: December 20, 2024
• Study Start: November 11, 2025
• Primary Completion (Estimated): December 11, 2028
• Study Completion (Estimated): February 11, 2029
• Last Updated: March 27, 2026

Record last verified: 2026-03

Locations

GU (1); FR (40)