Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05124977
Other study ID # APHP200011
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date September 20, 2022
Est. completion date March 2026

Study information

Verified date November 2023
Source Assistance Publique - Hôpitaux de Paris
Contact Arnaud Foucrier
Phone +33 1 40 87 52 33
Email arnaud.foucrier@aphp.fr
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Increasing emergence of multidrug resistant (MDR) bacteria worldwide is now considered one of the most urgent threats to global health. The association between increase of antibiotics consumption and resistance emergence has been well documented for all patients admitted to the Intensive care unit (ICU) who received antibiotic treatment and for patients treated for ventilator associated pneumonia (VAP). Reduction of use of antibiotics is a major point in the war against antimicrobial resistance. VAP is the first cause of healthcare-associated infections in ICU and more than half of antibiotics prescriptions in ICU are due to VAP. Once the diagnosis of pneumonia under MV has been made, initiation of antibiotic treatment must be prompt but there is no clear consensus on its duration. In the case of a good clinical response to treatment, it has been shown in some situations that short course antibiotics can be effective without side effects and antimicrobial stewardship initiatives can be applied successfully and effectively to the management of Community Acquired Pneumonia (CAP). The hypothesis is that an antimicrobial stewardship is possible in the treatment of VAP with no increase in the rate of all-cause mortality, treatment failure or occurrence of new episode of pneumonia. The objective is to investigate whether an antimicrobial stewardship for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would be non-inferior in terms of all-cause mortality, treatment failure or occurrence of new episode of pneumonia. This study will be a prospective, national multicenter (31 centers), phase III, comparative randomized (1:1), single-blinded clinical trial comparing two management strategies of treatment of pneumonia on the basis of two parallel arms: Experimental group: Antimicrobial stewardship based on daily clinical assessment of clinical cure. Control group: standard management: duration of appropriate antibiotic therapy for confirmed VAP according to guidelines.


Description:

Increasing emergence of multidrug resistant (MDR) bacteria worldwide is now considered one of the most urgent threats to global health. The association between increase of antibiotics consumption and resistance emergence has been well documented for all patients admitted to the Intensive care unit (ICU) who received antibiotic treatment1 and for patients treated for ventilator associated pneumonia (VAP). Reduction of use of antibiotics is a major point in the war against antimicrobial resistance. VAP is the first cause of healthcare-associated infections in ICU and more than half of antibiotics prescriptions in ICU are due to VAP. Current international guidelines define VAP as a pneumonia occurring>48 hours after endotracheal intubation and distinguishes early onset VAP occurring in the first five days after admission and late VAP, occurring after. Once the diagnosis of pneumonia under MV has been made, initiation of antibiotic treatment must be prompt but there is no clear consensus on its duration. In the case of a good clinical response to treatment, it has been shown in some situations that short course antibiotics can be effective without side effects and antimicrobial stewardship initiatives can be applied successfully and effectively to the management of Community Acquired Pneumonia (CAP). American guidelines strongly recommend a 7-day course of antibiotic therapy rather than a longer duration but remark that "there exist situations in which a shorter or longer duration of antibiotics may be indicated, depending upon the rate of improvement of clinical, radiologic, and laboratory parameters". The hypothesis is that an antimicrobial stewardship is possible in the treatment of VAP with no increase in the rate of all-cause mortality, treatment failure or occurrence of new episode of pneumonia. The objective is to investigate whether an antimicrobial stewardship for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would be non-inferior in terms of all-cause mortality, treatment failure or occurrence of new episode of pneumonia. This study will be a prospective, national multicenter (31 centers), phase III, comparative randomized (1:1), single-blinded clinical trial comparing two management strategies of treatment of pneumonia on the basis of two parallel arms: Experimental group: Antimicrobial stewardship based on daily clinical assessment of clinical cure. Control group: standard management: duration of appropriate antibiotic therapy for confirmed VAP according to guidelines. The primary endpoint is a hierarchical endpoint with a first non-inferiority criteria and a second efficacy criteria.


Recruitment information / eligibility

Status Recruiting
Enrollment 590
Est. completion date March 2026
Est. primary completion date September 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Diagnosis of microbiologically confirmed of first episode of VAP - Initial appropriate antibiotic therapy (whether empirical or not) - Written informed consent from the patient or a legal representative if appropriate. If absence of a legal representative the patient may be included in emergency procedure Definitive diagnosis of pneumonia (in agreement with international guidelines) is defined by association: - Patient under MV>48 hours at the time of the microbiological sampling - New pulmonary infiltrate of which an infectious origin is strongly suspected - Worsening oxygenation - Have the following clinical criteria within the 24 hours prior to the first dose of antibiotic therapy - Purulent tracheal secretions - And at least 1 of the following : documented fever (body temperature >38,3°C) or hypothermia (body temperature <35°C) or white blood cell (WBC) count >10,000 cells/mm3 or <4,000 cells/mm3 - Microbiological criteria (positive quantitative culture of a lower respiratory tract (LRT): bronchoalveolar lavage fluid (BAL) (significant threshold =10^4 colony-forming units/mL) or plugged telescopic catheter (PTC) (significant threshold = 10^3 colony-forming units/mL) or quantitative endotracheal aspirate (ETA) distal pulmonary secretion samples (significant threshold =10^5 colony-forming units/mL) Exclusion Criteria: - Patient under selective decontamination of the digestive tract - Duration of antibiotic therapy prior to inclusion > 72h (for any reason) appropriate to the germs found in the bacterial documentation of the first episode of VAP - Inclusion in another interventional study concerning antimicrobial strategies - Moribund (IGS II>80) - Thoracic trauma with Abbreviated Injury Scale (AIS) thorax = 3 - Severely immunocompromised patients (such as congenital immunodeficiency, neutropenia (<1leucocyte/ml or <0.5 neutrophil/ml) or acute hematologic malignancy or stem cell transplant, HIV infection with CD4 count below 200/mm3 - Patients undergoing immunosuppressive therapy and long term corticotherapy > 0.5 mg/kg - VAP due to: Pseudomonas aeruginosa, Carbapenem-resistant Acinetobacter spp, Carbapenem-resistant Enterobacteriaceae - VAP occurring in the context of co-infection of COVID-19 or other viral pneumonia (confirmed by RT-PCR) - Patients with empyema, necrotizing and abscessed pneumonia - Patients requiring extracorporeal oxygen therapy (ECMO), either veno-venous or veno-arterial - Pregnant women - No health insurance coverage

Study Design


Intervention

Drug:
Antimicrobial Stewardship
Antimicrobial stewardship based on daily clinical assessment of clinical cure. Discontinuation of appropriate antibiotic therapy antibiotics if criteria of clinical cure of confirmed pneumonia are met. Intensivists will perform clinical assessment daily in order to decide on the pursuit or discontinuation of antibiotic therapy.
Standard management
Standard management: duration of appropriate antibiotic for confirmed pneumonia fixed for 7 days according to guidelines. In the control group, intensivists will perform clinical assessment daily, but the antibiotic will not be discontinued until 7 days whatever the clinical cure.

Locations

Country Name City State
France Foucrier Clichy-sous-Bois

Sponsors (1)

Lead Sponsor Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary Investigate whether an AMS for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would be non-inferior in terms of all-cause mortality, treatment failure or occurrence of new episode of pneumonia The primary endpoint is a composite endpoint with non-inferiority criteria including:
1. all-cause mortality (ACM) measured at day 28 after initiation of therapy
28 days
Primary Investigate whether an AMS for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would be non-inferior in terms of all-cause mortality, treatment failure or occurrence of new episode of pneumonia The primary endpoint is a composite endpoint with non-inferiority criteria including:
2. Treatment failure defined by new signs of pneumonia within 72 hours after the end antibiotic treatment at the test of cure visit
28 days
Primary Investigate whether an AMS for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would be non-inferior in terms of all-cause mortality, treatment failure or occurrence of new episode of pneumonia The primary endpoint is a composite endpoint with non-inferiority criteria including:
3. New episode of microbiologically confirmed VAP from 72H after the end of antibiotic treatment to day 28 after initiation of VAP antibiotic treatment
28 days
Secondary Investigate whether an AMS for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would be non-inferior in term of all-cause mortality Rate of all-cause mortality 28 days after inclusion
Secondary Investigate whether an AMS for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would be non-inferior in term of occurrence of treatment failure Rate of treatment failure 28 days after inclusion
Secondary investigate whether an AMS for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would be non-inferior in term of occurrence of new episode of pneumonia Rate of new episode of VAP 28 days after inclusion
Secondary Investigate whether an AMS for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would increase the number of antibiotic free-alive days, from initiation of VAP antibiotic therapy to day 28 Number of antibiotic free alive-days 28 days after inclusion
Secondary Investigate whether an AMS for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would reduce at day 28 after inclusion of VAP antibiotic therapy the global DOOR score Global score constructed with the DOOR and RADAR 28 days after inclusion
Secondary Investigate whether an AMS for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would reduce at day 28 after inclusion the duration of invasive mechanical ventilation Duration of invasive MV 28 days after inclusion
Secondary Investigate whether an AMS for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would reduce at day 28 after inclusion the length of stay in intensive care unit Length of ICU stay 28 days after inclusion
Secondary To investigate whether an AMS for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would reduce at day 28 after inclusion the rate of VAP recurrence Rate of VAP recurrence 28 days after inclusion
Secondary Investigate whether an AMS for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would reduce at day 28 after inclusion the rate of complications of antibiotic therapy Rate of antibiotic related side effects 28 days after inclusion
Secondary Investigate whether an AMS for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would reduce at day 28 after inclusion the rate of acquisition of carriage of MDR bacteria Rate of acquisition of MDR bacteria 28 days after inclusion
Secondary Investigate whether an AMS for VAP based on daily assessment of clinical cure and antimicrobial discontinuation, if it is obtained, would reduce at day 28 after inclusion: The rate of subsequent infection due to : carbapenem-resistant Enterobacteriaceae Rate of subsequent infection of MDR bacteria 28 days after inclusion
Secondary Study if an AMS based on daily clinical assessment of clinical cure of VAP versus standard management would improve survival at days 28 and 90 after inclusion Rate of death 28 and 90 days after inclusion
Secondary Study the adherence to the AMS strategy (in order to identify factors associated to this adherence) in the intervention group only at day 28 after inclusion Adherence to AMS strategy 28 days after inclusion
Secondary Assess the medico-economic impact of antimicrobial stewardship applied to VAP at day 28 after inclusion Total cumulative costs 28 days after inclusion
See also
  Status Clinical Trial Phase
Recruiting NCT03937947 - Traumatic Brain Injury Associated Radiological DVT Incidence and Significance Study
Not yet recruiting NCT04057625 - Transthoracic Ultrasound in the Diagnosis and Follow-up of Ventilator Associated Pneumonia N/A
Not yet recruiting NCT03267693 - Gastrointestinal Complications in Association With Oropharyngeal and Respiratory Infections in Mechanical Ventilation N/A
Completed NCT02078999 - Biomarkers in Patients Undergoing Mechanical Ventilation N/A
Completed NCT00726167 - Serum Procalcitonin Study in the Management of Ventilated Patients N/A
Recruiting NCT05331885 - A Human Monoclonal Antibody Against Staphylococcus Aureus Alpha Toxin in Mechanically Ventilated Adult Subjects - 2 Phase 3
Completed NCT05517759 - Application of VAP Bundle Among ICU Nurses
Active, not recruiting NCT04488510 - Pathogens Involved in Secondary Infections During Severe Forms of Covid-19 Pneumonia:
Completed NCT03917888 - Clinical Impact of Lung Ultrasound Monitoring for Diagnosis of VAP N/A
Not yet recruiting NCT06066489 - Effect of Educational Program About Preventive Care Bundle for Prevention of Ventilator Associated Pneumonia Among Newborns N/A
Completed NCT02096328 - Pharmacokinetics, Safety and Efficacy of POL7080 in Patients With Ventilator Associated Pseudomonas Aeruginosa Pneumonia Phase 2
Terminated NCT00771719 - Open Label Pharmacokinetic in Adult Patients With Ventilator-Associated Pneumonia Phase 1
Recruiting NCT05696093 - Efficacy of Cotrimoxazole as a De-escalation Treatment of Ventilator-Associated Pneumonia in Intensive Care Unit Phase 3
Recruiting NCT05354778 - HYDROcortisone Versus Placebo for Severe HospItal-acquired Pneumonia in Intensive Care Patients: the HYDRO-SHIP Study N/A
Not yet recruiting NCT06059040 - Effect of Eliminating Gastric Residual Volume Monitoring on Ventilator Associated Events N/A
Completed NCT04563104 - Lung Ultrasound in Procalcitonin- Guided Antibiotic Discontinuation in Ventilator Associated Pneumonia
Terminated NCT01975350 - Efficacy Study of Colistimethate Sodium Inhalation in Patients With Ventilator-associated Pneumonia
Recruiting NCT06000761 - Frequent Standardized Oral Care Using Human Milk in the Neonatal Intensive Care Unit N/A
Not yet recruiting NCT03294837 - Treatment of Ventilator Associated Pneumonia in Pediatric Intensive Care Unit N/A
Completed NCT02928042 - Inhibition Effects of Probiotics on Pathogens Associated With VAP N/A