An interventional study of control group and Conservative strategy in Ventilator-Associated Pneumonia (VAP), sponsored by Nantes University Hospital. Recruiting at 42 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-21.
Sponsored by Nantes University Hospital · Not applicable, Interventional, and Treatment
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.
420 studies on the registry are indexed under Pneumonia, Ventilator-Associated; 85 are open to participants now.
This study's planned enrollment of 686 is above the median of 115 across 276 interventional studies indexed under Pneumonia, Ventilator-Associated.
Browse Pneumonia, Ventilator-Associated studies →Nantes University Hospital is the lead sponsor of 839 studies on the registry; 195 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria:
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) :
plus at least two of the following:
Non-inclusion Criteria:
Criteria for severe ventilator-associated pneumonia defined as:
defined as :
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Usual Care
Procedure: control group
Conservative strategy
Procedure: Conservative strategy
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.
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).
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).
Time frame: From day 0 to day 28
Sequential Organ Failure Assessment (SOFA) score
Daily Sequential Organ Failure Assessment (SOFA)
Time frame: From day 0 to day 7
Modified clinical pulmonary infection score (mCPIS)
Daily mcPIS
Time frame: From day 0 to day 7
Clinical cure
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
Time frame: day 7
Invasive mechanical ventilation duration
Days of invasive mechanical ventilation
Time frame: From day 0 to day 28
Ventilator free days
Time frame: From day 0 to day 28
Use of vasopressors
Days on vasopressors
Time frame: From day 0 to day 28
Use of renal replacement therapy
Days on renal replacement therapy
Time frame: From day 0 to day 28
Mortality rates
ICU discharge mortality rates
Time frame: ICU discharge, an average of 10 days
Mortality rates
Mortality rates at day 28
Time frame: day 28
Mortality rates
Mortality rates at day 90
Time frame: day 90
Mortality rates
Mortality rates at hospital discharge
Time frame: Hospital discharge, an average of 20 days
ICU stay lenghts
ICU stay lenghts (days)
Time frame: From day 0 until the day of discharge from ICU, an average of 10 days
Hospital stay lenghts
Hospital stay lenghts (days)
Time frame: 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
Incidence of ventilator associated pneumonia related bacteria
Time frame: 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
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.
Time frame: From day 0 until the day of discharge from Hospital, an average of 20 days
Incidence of noscomial infections between randomisation and hospital discharge
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
Time frame: 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)
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).
Time frame: 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
Antibiotic-free days
Time frame: day 10
Number of antibotic therapy days by 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.
Time frame: day 28
Broad-spectrum days of therapy (DOT) by 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)
Time frame: day 28
Carbapenom days of therapy (DOT) by 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).
Time frame: day 28
Ventilator associated pneumonia antibiotic therapy
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)
Time frame: From day 0 to day 28
Descriptive antibiotic therapy data
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
Time frame: From day 0 to day 28
Descriptive bacteriological data
gram stain, organisms recovered (cultured and/or identified by PCR), and antimicrobial resistance profiles
Time frame: 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
Proportion of patients with confirmed ventilator associated pneumonia
Time frame: 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
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)
Time frame: 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
* 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
Time frame: 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)
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.
Time frame: day 90
Cost-utility analysis (CUA)
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.
Time frame: day 90
EQ-5D-5L EuroQol score
Quality of life will be assessed using the EQ5D EuroQol score
Time frame: day 0
EQ-5D-5L EuroQol score
Quality of life will be assessed using the EQ5D-5L EuroQol score
Time frame: day 28
EQ-5D-5L EuroQol score
Quality of life will be assessed using the EQ5D-5L EuroQol score
Time frame: day 90
Started Nov 2025 (actual). Primary completion is estimated for Dec 2028, 37 months after the start.
Of 81 non-industry interventional studies with no phase under Pneumonia, Ventilator-Associated, half reached primary completion within 20 months of starting (the median), counting those still running; a quarter within 10 and three quarters within 38. This study's planned 37 months is above that.
Counting every sponsor, half of 82 studies reached it within 20 months; a quarter within 10 and three quarters within 36.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Pneumonia, Ventilator-Associated →