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

Not Applicable
Not yet recruiting
Conditions
Registration Number
NCT06743529
Lead Sponsor
Nantes University Hospital
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 bacteriolo...

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
686
Inclusion Criteria
  • Invasive mechanical ventilation for longer than 48 hours
  • Respiratory sampling (method at the physician's discretion, according to local protocol) for a first episode of suspected ventilator-associated pneumonia (meeting the prespecified criteria)
  • 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.

  • Pregnancy, recent delivery, or breastfeeding

  • Correctional facility inmate, adult under guardianship

  • Patient under legal protection

  • Life expectancy less than 48 hours and/or decision to withhold and/or withdraw life-sustaining therapies

  • Organ donor reanimation

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Exclusion Criteria

Not provided

Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
Assessment of the risk to the patient of delaying antibiotic therapy until bacteriological results are availableFrom 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) neit...

Secondary Outcome Measures
NameTimeMethod
Sequential Organ Failure Assessment (SOFA) scoreFrom day 0 to day 7

Daily Sequential Organ Failure Assessment (SOFA)

Modified clinical pulmonary infection score (mCPIS)From day 0 to day 7

Daily mcPIS

Clinical cureday 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

Invasive mechanical ventilation durationFrom day 0 to day 28

Days of invasive mechanical ventilation

Ventilator free daysFrom day 0 to day 28
Use of vasopressorsFrom day 0 to day 28

Days on vasopressors

Mortality ratesHospital discharge, an average of 20 days

Mortality rates at hospital discharge

ICU stay lenghtsFrom day 0 until the day of discharge from ICU, an average of 10 days

ICU stay lenghts (days),

Hospital stay lenghtsFrom day 0 until the day of discharge from Hospital, an average of 20 days

Hospital stay lenghts (days)

Incidence of ventilator associated pneumonia related abscessFrom day 0 until the day of discharge from ICU, an average of 10 days
Incidence of ventilator associated pneumonia related bacteriaFrom 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 stayFrom 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 biomarke...

Incidence of noscomial infections between randomisation and hospital dischargeFrom 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

Incidence of in-hospital nosocomial infections by multiresistant bacteria (MRB)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).

Incidences of allergies and of diarrheaFrom day 0 until the day of discharge from Hospital, an average of 20 days
Antibiotic-free daysday 10
Number of antibotic therapy days by day 28day 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.

Broad-spectrum days of therapy (DOT) by day 28day 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)

Carbapenom days of therapy (DOT) by day 28day 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).

Ventilator associated pneumonia antibiotic therapyFrom 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)

Descriptive antibiotic therapy dataFrom day 0 to day 28
Descriptive bacteriological dataFrom day 0 to day 28
Descriptive clinical, laboratory and radiological data 48 hours before ventilator associated pneumonia suspicion48 hours before ventilator asociated pneumonia suspicion
Proportion of patients with confirmed ventilator associated pneumoniaFrom day 0 to day 28
Number of patients given active/inactive/unnecessary antibiotic therapy on day 0 and on the day of antibiotic therapy initiationDay 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 ...

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 armDay 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
...

EQ-5D-5L EuroQol scoreday 0

Quality of life will be assessed using the EQ5D EuroQol score

Quality of lifeday 90

Quality of life will be assessed using the EQ5D-5L EuroQol score

Incremental cost-utility ratio (ICUR)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.

Trial Locations

Locations (40)

CHU Nice - Hôpital de l'Archet

🇫🇷

Nice, France

GHRU de Nîmes

🇫🇷

Nîmes, France

CHR d'Orléans

🇫🇷

Orléans, France

APHP - Hôpital Cochin

🇫🇷

Paris, France

APHP - Hôpital Tenon

🇫🇷

Paris, France

CH de Pau

🇫🇷

Pau, France

CHU Nice -Hôpital Pasteur

🇫🇷

Nice, France

CHU Amiens

🇫🇷

Amiens, France

CHU Angers

🇫🇷

Angers, France

CH Angoulème

🇫🇷

Angoulème, France

CH Argenteuil

🇫🇷

Argenteuil, France

CH Avignon

🇫🇷

Avignon, France

Hôpital Nord Franche Comté

🇫🇷

Belfort, France

CH Béthune

🇫🇷

Béthune, France

CH Simone Veil

🇫🇷

Cannes, France

CH Public du Cotentin

🇫🇷

Cherbourg En Cotentin, France

CH Cholet

🇫🇷

Cholet, France

CHU Clermont-Ferrand

🇫🇷

Clermont-Ferrand, France

CH Dax

🇫🇷

Dax, France

CHU Dijon

🇫🇷

Dijon, France

APHP - Hôpital Raymond Poincaré

🇫🇷

Garches, France

CHD Vendée

🇫🇷

La Roche-sur-Yon, France

CH Versailles

🇫🇷

Le Chesnay, France

CH Le Mans

🇫🇷

Le Mans, France

CHRU Lille

🇫🇷

Lille, France

GHB Sud- Hôpital de Lorient

🇫🇷

Lorient, France

CHU de Lyon - Hôpital Edouard Herriot

🇫🇷

Lyon, France

CH de Mont de Marsan

🇫🇷

Mont-de-Marsan, France

CHU Nantes

🇫🇷

Nantes, France

CHU Rennes

🇫🇷

Rennes, France

CH de Saint-Nazaire

🇫🇷

Saint Nazaire, France

CH de Saint-Malo

🇫🇷

Saint-Malo, France

CHRU de Strasbourg - Nouvel Hôpital Civil

🇫🇷

Strasbourg, France

CHRU de Strasbourg -Hôpital de Hautepierre

🇫🇷

Strasbourg, France

Hôpital Foch

🇫🇷

Suresnes, France

CHRU De Tours

🇫🇷

Tours, France

CH de Valence

🇫🇷

Valence, France

CH de Valenciennes

🇫🇷

Valenciennes, France

CH Bretagne Atlantique

🇫🇷

Vannes, France

CHU La Guadeloupe

🇹🇫

Pointe-à-Pitre, French Southern Territories

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