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

March 23, 2026 updated by: Nantes University Hospital

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

686

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Arles, France, 13637
      • Avignon, France, 84000
      • Belfort, France, 90000
        • Recruiting
        • Hopital Nord Franche Comte
        • Contact:
      • Bordeaux, France, 33076
      • Bordeaux, France
      • Cannes, France, 06414
        • Recruiting
        • CH Simone VEIL
        • Contact:
      • Cherbourg, France, 50102
      • Cholet, France, 49325
      • Clermont-Ferrand, France, 63003
      • Dax, France, 40107
        • Recruiting
        • CH Dax
        • Contact:
      • Dijon, France, 21033
      • Garches, France, 92380
        • Recruiting
        • APHP - Hôpital Raymond Poincaré
        • Contact:
      • La Roche-sur-Yon, France, 85025
      • Le Chesnay, France, 78157
        • Recruiting
        • CH Versailles
        • Contact:
      • Le Mans, France, 72000
        • Recruiting
        • CH Le mans
        • Contact:
      • Le Puy-en-Velay, France, 43000
      • Lille, France, 59037
      • Lorient, France, 56100
        • Recruiting
        • GHB Sud- Hôpital de Lorient
        • Contact:
      • Lyon, France, 69437
        • Recruiting
        • CHU de Lyon - Hopital Edouard Herriot
        • Contact:
      • Melun, France, 77000
      • Mont-de-Marsan, France, 40000
      • Nice, France, 06100
        • Recruiting
        • CHU Nice -Hôpital Pasteur
        • Contact:
      • Nice, France, 06200
        • Recruiting
        • CHU Nice - Hôpital de l'Archet
        • Contact:
      • Orléans, France, 45100
      • Paris, France, 75014
      • Paris, France, 75020
        • Recruiting
        • APHP - Hôpital Tenon
        • Contact:
      • Pau, France, 64000
      • Rennes, France, 35033
      • Saint-Nazaire, France, 44600
      • St-Malo, France, 35403
        • Recruiting
        • CH de Saint-Malo
        • Contact:
      • Strasbourg, France, 67091
      • Strasbourg, France, 67098
      • Suresnes, France, 92150
      • Tours, France, 37044
        • Recruiting
        • Chru De Tours
        • Contact:
      • Valenciennes, France, 59300
      • Vannes, France, 56017
    • France
      • Angers, France, France, 49000
      • Angoulème, France, France, 16000
      • Argenteuil, France, France, 95100
      • Nantes, France, France, 44000
  • Guadeloupe
      • Pointe-à-Pitre, Guadeloupe, 97159

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Immediate strategy
Usual Care
Procedure: control group
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.
Experimental: Conservative strategy
Procedure: Conservative strategy
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients who die whithin 28 days or are still on invasive mechanical ventilation on day 28
Time Frame: From day 0 to 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality rates
Time Frame: ICU discharge, an average of 10 days
ICU discharge mortality rates
ICU discharge, an average of 10 days
Sequential Organ Failure Assessment (SOFA) score
Time Frame: From day 0 to day 7
Daily Sequential Organ Failure Assessment (SOFA)
From day 0 to day 7
Modified clinical pulmonary infection score (mCPIS)
Time Frame: From day 0 to day 7
Daily mcPIS
From day 0 to day 7
Clinical cure
Time Frame: day 7
Clinical cure is defined as the combination of resolution of signs and symptoms present at enrollment, and improvement or lack of progression of radiological signs
day 7
Invasive mechanical ventilation duration
Time Frame: From day 0 to day 28
Days of invasive mechanical ventilation
From day 0 to day 28
Ventilator free days
Time Frame: From day 0 to day 28
From day 0 to day 28
Use of vasopressors
Time Frame: From day 0 to day 28
Days on vasopressors
From day 0 to day 28
Mortality rates
Time Frame: day 28
Mortality rates at day 28
day 28
Mortality rates
Time Frame: day 90
Mortality rates at day 90
day 90
Mortality rates
Time Frame: Hospital discharge, an average of 20 days
Mortality rates at hospital discharge
Hospital discharge, an average of 20 days
Hospital stay lenghts
Time Frame: From day 0 until the day of discharge from Hospital, an average of 20 days
Hospital stay lenghts (days)
From day 0 until the day of discharge from Hospital, an average of 20 days
Incidence of ventilator associated pneumonia related abscess
Time Frame: From day 0 until the day of discharge from ICU, an average of 10 days
From day 0 until the day of discharge from ICU, an average of 10 days
Incidence of ventilator associated pneumonia related bacteria
Time Frame: From day 0 until the day of discharge from ICU, an average of 10 days
From day 0 until the day of discharge from ICU, an average of 10 days
Incidence and timing of subsequent ventilator associated pneumonia during the hospital stay
Time Frame: From day 0 until the day of discharge from Hospital, an average of 20 days
Incidence and timing of subsequent ventilator associated pneumonia during the hospital stay: relapse, recurrence, superinfection, ventilator associated pneumonia occurrence after a suspected but refuted ventilator associated pneumonia episode; recurrence is defined as improvements in manifestations (fever, secretions, vasopressor needs, inflammatory biomarkers, and chest radiograph infiltrates) after 7 days' treatment with at least ne antibiotic active on all documented bacteria, followed by the return or worsening of these manifestations with a new respiratory sample (culture, with or without PCR) positive for at least one bacterial species in significant concentrations; the same scenario with a respiratory sample positive for at least one of the initial causative bacteria defined relapse; no improvement in manifestations after 7 days' active treatment with a respiratory sample positive for at least one of the initial causative bacteria defined superinfection.
From day 0 until the day of discharge from Hospital, an average of 20 days
Incidence of noscomial infections between randomisation and hospital discharge
Time Frame: From day 0 until the day of discharge from Hospital, an average of 20 days
Nosocomial infections including ventilator asssociated pneumonia, nosocomial pneumonia, bacteremia, catheter-related bloodstream infection, urinary-tract infection, soft-tissue infection, C. difficile infection, and other infections
From day 0 until the day of discharge from Hospital, an average of 20 days
Incidence of in-hospital nosocomial infections by multiresistant bacteria (MRB)
Time Frame: From day 0 until the day of discharge from Hospital, an average of 20 days
Defined as any of the following: methicillin-resistant Staphylococcus aureus (MRSA), glycopeptide-intermediate S. aureus (GISA), vancomycin-resistant Enterococcus (VRE), extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-e), carbapenemase-producing Enterobacterales (CPE), and imipenem-resistant Acinetobacter baumannii (IRAB).
From day 0 until the day of discharge from Hospital, an average of 20 days
Incidences of allergies and of diarrhea
Time Frame: From day 0 until the day of discharge from Hospital, an average of 20 days
From day 0 until the day of discharge from Hospital, an average of 20 days
Antibiotic-free days
Time Frame: day 10
day 10
Number of antibotic therapy days by day 28
Time Frame: day 28
computed as days of therapy (DOT), defined as the number of days on AT, with each day multiplied by the number of individual antimicrobial agents given on that day, irrespective of the number of doses given.
day 28
Broad-spectrum days of therapy (DOT) by day 28
Time Frame: day 28
(ceftazidime, piperacillin/tazobactam, cefepime, fluoroquinolones, carbapenems, or new AT for multidrug-resistant Gram-negative bacilli) (number of days on broad-spectrum AT multiplied by the number of individual antimicrobial agents given on each of those days, irrespective of the number of doses given)
day 28
Carbapenom days of therapy (DOT) by day 28
Time Frame: day 28
Carbapenem DOT by day 28 (number of calendar days during which the patient received at least one carbapenem dose multiplied by the number of individual antimicrobial agents given on each of those days, until day 28, irrespective of the number of doses given).
day 28
Ventilator associated pneumonia antibiotic therapy
Time Frame: From day 0 to day 28
Descriptive data : dual therapy, median time from respiratory sampling to AT, duration, de-escalation (defined as empirical AT stopped or number of empirical antimicrobials decreased or spectrum of empirical AT narrowed, based on AST results)
From day 0 to day 28
Descriptive clinical, laboratory and radiological data 48 hours before ventilator associated pneumonia suspicion
Time Frame: 48 hours before ventilator asociated pneumonia suspicion
48 hours before ventilator asociated pneumonia suspicion
Proportion of patients with confirmed ventilator associated pneumonia
Time Frame: From day 0 to day 28
From day 0 to day 28
Number of patients given active/inactive/unnecessary antibiotic therapy on day 0 and on the day of antibiotic therapy initiation
Time Frame: Day 0 and on the day of antibiotic therapy initiation, an average of 1 day
Number of patients given active/inactive/unnecessary antibiotic therapy on day 0 and on the day of antibiotic therapy initiation (with active defined as at least one antimicrobial agent active against each bacterial species isolated from respiratory samples in concentrations greater than prespecified thresholds, based on AST; inactive defined as not meeting criteria for active AT; and unnecessary defined as antibiotic therapy given before sample results with these being negative)
Day 0 and on the day of antibiotic therapy initiation, an average of 1 day
Number of patients with suitable antibotic therapy (defined as active antibiotic therapy or spared antibiotic therapy as defined below) on day 0 and on the day of antibiotic therapy initiation in the conservative strategy arm
Time Frame: Day 0 and on the day of antibiotic therapy initiation, until discharge from intensive care unit or up to 28 days
  • Number of patients given substantiated antibotic therapy defined as started upon receipt of positive respiratory-sample culture and/or PCR test results
  • Number of patients given rescue antibotic therapy defined as started, in a conservative group patient, after sampling but before culture and/or PCR results, due to the development of ventilator associated pneumonia severity criteria (shock or severe ARDS)
  • Number of patients spared antibotic therapy for the suspected ventilator associated pneumonia episode, that is, not given antibotic therapy after sampling and having negative respiratory-sample results
Day 0 and on the day of antibiotic therapy initiation, until discharge from intensive care unit or up to 28 days
Incremental cost-utility ratio (ICUR)
Time Frame: day 90
The incremental cost-utility ratio (ICUR, cost per quality-adjusted life year [QALY] gained) of the two strategies will be computed from a collective perspective and with a 90-day time horizon then compared between the two groups.
day 90
Descriptive antibiotic therapy data
Time Frame: From day 0 to day 28
Ventilator associated pneumonia antibiotic therapy: antimicrobial(s), dual therapy, median time from respiratory sampling to antibiotic therapy, duration, de-escalation (defined as empirical AT stopped or number of empirical antimicrobials decreased or spectrum of empirical antibiotic therapy narrowed, based on AST results) , antibiotic therapy for reasons other than suspected VAP: antimicrobial, duration, reason
From day 0 to day 28
Descriptive bacteriological data
Time Frame: From day 0 to day 28
gram stain, organisms recovered (cultured and/or identified by PCR), and antimicrobial resistance profiles
From day 0 to day 28
Use of renal replacement therapy
Time Frame: From day 0 to day 28
Days on renal replacement therapy
From day 0 to day 28
ICU stay lenghts
Time Frame: From day 0 until the day of discharge from ICU, an average of 10 days
ICU stay lenghts (days)
From day 0 until the day of discharge from ICU, an average of 10 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
EQ-5D-5L EuroQol score
Time Frame: day 0
Quality of life will be assessed using the EQ5D EuroQol score
day 0
Cost-utility analysis (CUA)
Time Frame: day 90

To determine whether, in patients who have suspected non-severe VAP (no septic shock or severe ARDS), postponing AT until VAP is confirmed (by a positive respiratory-sample culture and/or PCR) is cost-efficient, compared to the immediate strategy, from a collective perspective (considering costs to the National Health Insurance (NHI) system and hospital) and with a 90-day time horizon. A cost-utility analysis (CUA) will be performed.

The effectiveness of the two compared strategies will be assessed in terms of potential changes in quality of life and survival (CUA).c.
day 90
EQ-5D-5L EuroQol score
Time Frame: day 28
Quality of life will be assessed using the EQ5D-5L EuroQol score
day 28
EQ-5D-5L EuroQol score
Time Frame: day 90
Quality of life will be assessed using the EQ5D-5L EuroQol score
day 90

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nantes University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 11, 2025

Primary Completion (Estimated)

December 11, 2028

Study Completion (Estimated)

February 11, 2029

Study Registration Dates

First Submitted

December 10, 2024

First Submitted That Met QC Criteria

December 16, 2024

First Posted (Actual)

December 20, 2024

Study Record Updates

Last Update Posted (Actual)

March 27, 2026

Last Update Submitted That Met QC Criteria

March 23, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RC24_0466

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Ventilator-Associated Pneumonia (VAP)

Clinical Trials on control group

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Estonia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe