• Delayed Antibiotic Therapy in Non-severe Ventilator Acquired Pneumonia (VAP)

  NCT05205525

  CompletedObservationalUpdated Mar 8, 2023
• Antimicrobial Stewardship For Ventilator Associated Pneumonia in Intensive Care

  NCT05124977

  RecruitingInterventionalNot ApplicableUpdated May 25, 2025
• Combined Use of a Respiratory Multiplex PCR and Algorithm-based Therapy to Improve Early Optimization of Antibiotic Therapy in Critically Ill Patients With Ventilator-associated Pneumonia

  NCT07403474

  Not yet recruitingInterventionalPhase 4Updated Feb 12, 2026
• Bronchoscopy vs. Clinical Pulmonary Infection Score Guided Approach in Suspected Ventilator-Associated Pneumonia (VAP)

  NCT00588588

  WithdrawnInterventionalPhase 3Updated Sep 26, 2023
• Empiric Antibiotic Therapy for Ventilator-acquired Pneumonia With Gram-negative Bacilli in Intensive Care

  NCT02127528

  Unknown statusObservationalUpdated Apr 18, 2016
• Impact of the Duration of Antibiotics on Clinical Events in Patients With Pseudomonas Aeruginosa Ventilator-associated Pneumonia (iDIAPASON)

  NCT02634411

  CompletedInterventionalNot ApplicableUpdated Oct 20, 2021

ClinicalTrials.gov ID

NCT06743529

Lead Sponsor

Nantes University HospitalOTHER

Overall Status

Recruiting

Study Type

Interventional

Phase

Not Applicable

Enrollment

686Estimated

Last Update Posted

Mar 27, 2026Actual

Start Date

Nov 11, 2025Actual

Primary Completion Date

Dec 11, 2028Estimated

Completion Date

Feb 11, 2029Estimated

Official Title

Immediate Versus Substantiated Antibiotic Therapy in Suspected Non-Severe Ventilator-Associated Pneumonia: A Randomized Controlled Trial

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.

• Ventilator-Associated Pneumonia (VAP)

• control group
• Conservative strategy

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria:

• 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

Non-inclusion Criteria:

• 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
  • within the last 3 months
  • hematopoietic stem-cell transplant or organ transplant with chronic immunosuppressant therapy
  • HIV infection with CD4<50/mm3
  • chronic corticosteroid use (>0.5 mg/kg day for at least one month within the last three months).

• Patient already on Antibiotic Therapy of predicted duration ≥4 weeks (endocarditis, spondylodiscitis, abscess...)

• Previous ventilator-associated pneumonia suspicion with sampling and/or Antibiotic Therapy for suspected ventilator-associated pneumonia

• Previous inclusion in the trial

• Patient included in an interventional study on ventilator-associated pneumonia management with the same primary endpoint.

• Pregnancy, recent delivery, or breastfeeding

• Correctional facility inmate, adult under guardianship

• Patient under legal protection

• Life expectancy less than 48 h and/or decision not to treat potential pneumonia acquired under mechanical ventilation in the context of limiting/discontinuing treatment.

• Organ donor reanimation

Primary Purpose

Treatment

Allocation

Randomized

Interventional Model

Parallel Assignment

Masking

None (Open Label)

Lead Sponsor

Nantes University HospitalOTHER

auveta@ch-dax.fr05 58 90 55 44 ext. +33

stanislas.deguillebon@ch-pau.fr05 59 92 48 49 ext. +33