Impact of the Duration of Antibiotics on Clinical Events in Patients With Pseudomonas Aeruginosa Ventilator-associated Pneumonia (iDIAPASON)

NCT02634411 | Completed DMC

• 3 other identifiers: P 140923AOM 14515IDRCB n°: 2015-A00375-44
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

Brief Summary

Ventilator-associated pneumonia (VAP) accounts for 25% of infections in intensive care units (Réseau RAISIN 2012). A short duration (8 days; SD) vs. long duration (15 days; LD) of antibiotic therapy has a comparable clinical efficacy with less antibiotic use and less multidrug-resistant pathogens (MDR) emergence. These results have led the American Thoracic Society to recommend SD therapy for VAP, with the exception of documented VAP of non-fermenting Gram negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA-VAP), due to the absence of studies focusing specifically on PA-VAP. Thus the beneficial effect of SD therapy in PA-VAP is still a matter of debate. In a small (n=127) subgroup analysis, a higher rate of recurrence with SD therapy (n=21, 32.8%) has been observed compared with LD therapy group (n=12, 19.0%). Unfortunately, the definition of recurrence was essentially based on microbiological rather than clinical data, and the higher rate of recurrence observed could rather reflect a higher rate of colonization more than a new infection. Interestingly, a trend for a lower rate of mortality was also observed in the SD group (n=15, 23.4%) compared with the LD group (n=19, 30.2%), but this study was clearly underpowered to detect a difference of mortality between groups. The two strategies were considered as not different, for the risk of mortality in a recent meta-analysis, performed on the very few available studies (n=2), that (OR = 1.33, 95% CI \[0.33 to 5.26\] for SD vs. LD strategies respectively). However, this conclusion remains questionable considering the large confidence interval of the risk and the power of these studies. Primary objective and assessment criterion: To assess the non-inferiority of a short duration of antibiotics (8 days) vs. prolonged antibiotic therapy (15 days) in P. aeruginosa ventilator-associated pneumonia (PA-VAP) on a composite end-point combining Day-90 mortality and PA-VAP recurrence rate during hospitalization in the ICU. Study Design : Randomized, open-labeled non inferiority controlled trial 32 French Intensive Care Units participating to the study Research period: Total study duration: 27 months Inclusion period: 24 months Duration of participation for a patient: 90 days

Conditions

Ventilator-Associated Pneumonia

Keywords

Ventilator Associated; Pneumonia; Antibiotic treatment; Pseudomonas aeruginosa

Outcome Measures

Primary Outcomes (1)

• A composite endpoint of morbi-mortality combining Day-90 mortality and PA-VAP recurrence rate during hospitalization in the ICU (within 90 days).

  A composite endpoint combining Day-90 mortality and PA-VAP recurrence rate during hospitalization in the ICU (within 90 days). Recurrence will be defined a posteriori by 3 independent experts with predefined criteria: clinical suspicion of VAP (≥ two criteria including: fever\> 38.5 ° C, leukocytosis \> 10 Giga/L or leukopenia \< 4 Giga/L, purulent tracheobronchial secretions and a new or persistent infiltrate on chest radiography) associated with a positive quantitative culture of a respiratory sample (bronchoalveolar lavage fluid (significant threshold ≥104 colony-forming units/mL) or plugged telescopic catheter (significant threshold ≥103 colony-forming units/mL) or quantitative endotracheal aspirate distal pulmonary secretion samples (significant threshold ≥106 colony-forming units/mL)).

  90 days after effective antibiotherapy

Secondary Outcomes (7)

• Measure of mortality rate (%) in the ICU

  Day 30 and Day 90 after effective antibiotherapy

• Measure of morbidity in ICU by duration of mechanical ventilation (days)

  Day 30 and Day 90 after effective antibiotherapy

• Measure of morbidity in ICU by duration of hospitalization in ICU (days)

  Day 30 and Day 90 after effective antibiotherapy

• Acquisition of MDR during the hospitalization in the ICU.

  during stay in the ICU : up to 90 days

• Exposure to antibiotics during the hospitalization in the ICU (days)

  during stay in the ICU : up to 90 days

Study Arms (2)

8 days of effective antibiotic treatment

EXPERIMENTAL

Antibiotic treatment should be started just after realization of bacteriological sampling, and then converted into a narrow-spectrum therapy, based on culture results, for a total duration of effective antibiotic therapy against PA of 8 days.

Drug: 8 days of effective antibiotic treatment

15 days of effective antibiotic treatment

SHAM COMPARATOR

Antibiotic treatment should be started just after realization of bacteriological sampling, and then converted into a narrow-spectrum therapy, based on culture results, for a total duration of effective antibiotic therapy against PA of 15 days.

Drug: 15 days of effective antibiotic treatment

Interventions

8 days of effective antibiotic treatment DRUG

Antibiotics used for usual care in PA-VAP treatment : Penicillins, Cephalosporins, Monobactams, Carbapenems, Fluoroquinolones, Aminoglycosides (list not exhaustive). Antibiotic treatment should be started just after realization of bacteriological sampling, and then converted into a narrow-spectrum therapy, based on culture results, for a total duration of effective antibiotic therapy against pseudomona aeruginosa of 8 days.

8 days of effective antibiotic treatment

15 days of effective antibiotic treatment DRUG

Antibiotics used for usual care in PA-VAP treatment : Penicillins, Cephalosporins, Monobactams, Carbapenems, Fluoroquinolones, Aminoglycosides (list not exhaustive). Antibiotic treatment should be started just after realization of bacteriological sampling, and then converted into a narrow-spectrum therapy, based on culture results, for a total duration of effective antibiotic therapy against pseudomona aeruginosa of 15 days.

15 days of effective antibiotic treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients older than 18 years
• Mechanical ventilation ≥ 48 hours
• Documented Pseudomonas aeruginosa ventilator-associated pneumonia:
• Clinical suspicion (≥ two criteria including: fever\> 38.5°C,leukocytosis \> 10 Giga/L or leukopenia \< 4 Giga/L, purulent tracheobronchial secretions and a new or persistent infiltrate on chest radiography).
• Documented Pseudomonas aeruginosa positive quantitative culture of a respiratory sample: bronchoalveolar lavage fluid (significant threshold, \>104cfu/ml) or plugged telescopic catheter (significant threshold, \>103cfu/ml) or quantitative endotracheal aspirate (significant threshold, \>106cfu/ml).
• Written informed consent
• Patient affiliated to French social security

You may not qualify if:

• Immunocompromised patients (HIV, immunosuppressive therapy, corticosteroids\> 0.5 mg / kg per day for more than a month)
• Patients receiving antibiotic therapy for extrapulmonary infection
• Patients in whom a procedure of withdrawing life-sustaining treatment has been established
• Pregnancy
• Patients included in another interventional study
• Chronic pulmonary colonization with Pseudomonas aeruginosa: patients with Chronic Obstructive Pulmonary Disease (COPD) or bronchiectasis, with a positive respiratory sample at infra threshold rate for Pseudomonas aeruginosa (ie\<103 CFUs/mL for protected specimen brush or \<106 CFUs/mL for tracheal aspirate), obtained in the absence of pneumonia or exacerbation during the 6 months before the ICU admission.
• Patient under guardianship or curatorship

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Anesthesiology and Critical Care Medicine Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière

Paris, 75571, France

Location

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MeSH Terms

Conditions

Pneumonia, Ventilator-Associated; Pneumonia; Pseudomonas Infections

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Study Officials

• Adrien Bouglé, MD

  APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2015
• First Posted: December 18, 2015
• Study Start: June 3, 2016
• Primary Completion: August 16, 2018
• Study Completion: August 16, 2018
• Last Updated: October 20, 2021

Record last verified: 2021-10

Locations

FR (1)