Ventilator-Associated PneumoniaiDIAPASONNCT02634411
Impact of the Duration of Antibiotics on Clinical Events in Patients With Pseudomonas Aeruginosa Ventilator-associated Pneumonia (iDIAPASON)
A study testing 8 days of effective antibiotic treatment and 15 days of effective antibiotic treatment in people with Ventilator-Associated Pneumonia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ventilator-Associated Pneumonia
- What is being tested?
- 8 days of effective antibiotic treatment and 15 days of effective antibiotic treatment
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 190 participants
- Where
- 1 siteFrance
- Study dates
- 3 Jun 2016to 16 Aug 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
France1 site
Anesthesiology and Critical Care Medicine Institut de Cardiologie, Groupe Hospitalier Pitié-Salpêtrière
Paris, 75571
About this study
Official title: Impact of the Duration of Antibiotics on Clinical Events in Patients With Pseudomonas Aeruginosa Ventilator-associated Pneumonia : a Randomized Controlled Study (iDIAPASON)
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.
Read more
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
Read the detailed description
Ventilator-associated pneumonia (VAP) is a major cause of morbidity and mortality in the ICU, accounting for 25% of infections in intensive care units (Réseau RAISIN 2012). From 1975 to 2003, the incidence of hospital-acquired pneumonia caused by Pseudomonas aeruginosa (PA) has almost doubled, from 9.6% to 18.1%. In a US national large-scale survey, PA was the most frequently isolated gram-negative aerobic bacterium from ICUs (23%) and also the most frequent bacterium isolated from the respiratory tract (31.6%).
PA-VAP is associated with a high mortality ranging from 40% up to 69%, and with high rates of recurrence despite adequate antimicrobial therapy. In a large randomized trial regarding the optimal duration of antibiotic therapy in overall VAPs, the rate of recurrence among the subgroup of non-fermenting Gram negative bacilli (NF-GNB) documented VAP varied between 19.0% and 32.8%, according to the randomization arm. Finally, a recently published cohort about 393 PA-VAP in 314 patients, the composite criteria failure treatment (death and recurrence) occured in 112 cases (28.5%).
Hypothesis A short duration antibiotherapy (8 days) vs. long duration antibiotherapy (15 days) in treatment of Pseudomonas aeruginosa Ventilator-Associated Pneumonia (PA-VAP) is safe and not associated with an increased mortality or recurrence rate of PA-VAP.
The demonstration of this hypothesis could lead to decrease antibiotic exposure during the hospitalization in the Intensive Care Unit (ICU) and in turn reduce the acquisition and the spread of multidrug-resistant pathogens (MDR).
Objectives
- Primary objective To assess the non-inferiority of a short duration of antibiotics (8 days) vs. prolonged antibiotic therapy (15 days) in Pseudomonas aeruginosa ventilator-associated pneumonia (PA-VAP) on morbi-mortality at 90 days.
- Secondary objectives
To compare between short and long duration of antibiotics on:
- mortality in the ICU
- morbidity in the ICU (mechanical ventilation, duration of hospitalization)
- exposure and acquisition of MDR during hospitalization
- number and types of extrapulmonary infections
Plan for the research
- Concise description of the primary and secondary assessment criteria
- Primary assessment criterion: 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)).
- Secondary assessment criteria:
- D30 and D90 mortality rate (%)
- Morbidity by: Duration of mechanical ventilation (days) Duration of hospitalization in ICU (days)
- Exposure to antibiotics during the hospitalization in the ICU (days)
- Number and types of extrapulmonary infections during the hospitalization in the ICU (n)
- Acquisition of MDR during the hospitalization in the ICU (swab sample of rectum and anterior nares)
- Description of research methodology
Randomized, open-labeled non inferiority trial comparing to parallel groups:
- 8 days of antibiotic therapy
- 15 days of antibiotic therapy
Antibiotic therapy Antibiotic treatment should be started just after realization of bacteriological sampling, without waiting for the result. The choice of initial antibiotic therapy will be left to the discretion of the physician but will be essentially based on the clinical context, previously antibiotic therapy, the presence or absence of risk factors for MDR (antibiotics or hospitalization in previous 90 days, current hospitalization ≥ 5 days, MV ≥ 5 days, supported in a dialysis center or residency in a nursing home), local epidemiological data, and finally if the patient is already known as being colonized by a MDR. Investigators would be strongly encouraged to convert this initial regimen into a narrow- spectrum therapy, based on culture results.
All antibiotics would be withdrawn, either at the end of day 8 or day 15, according to the randomization assignment, except those prescribed for a documented pulmonary infection recurrence before that day.
An algorithm for the initial prescription of antibiotics will be established in each ICU, the algorithm will be adapted whenever necessary to changes in the local ecology.
Number of centres participating 42 french Intensive Care Units (ICUs)
- Conditions
- Ventilator-Associated Pneumonia
- Being tested
- 8 days of effective antibiotic treatment, 15 days of effective antibiotic treatment
- Keywords
- Ventilator Associated, Pneumonia, Antibiotic treatment, Pseudomonas aeruginosa
- Medical subject headings
- Pneumonia, Ventilator-Associated, Pneumonia, Pseudomonas Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
8 days of effective antibiotic treatmentDrug
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.
15 days of effective antibiotic treatmentDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: 15 days of effective antibiotic treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)).
Measured: 90 days after effective antibiotherapy
Secondary outcomes (7)
Measure of mortality rate (%) in the ICU
Measured: Day 30 and Day 90 after effective antibiotherapy
Measure of morbidity in ICU by duration of mechanical ventilation (days)
Measured: Day 30 and Day 90 after effective antibiotherapy
Measure of morbidity in ICU by duration of hospitalization in ICU (days)
Measured: Day 30 and Day 90 after effective antibiotherapy
Acquisition of MDR during the hospitalization in the ICU.
Measured: during stay in the ICU : up to 90 days
Exposure to antibiotics during the hospitalization in the ICU (days)
Measured: during stay in the ICU : up to 90 days
Number of extrapulmonary infections during the hospitalization in the ICU
Measured: during stay in the ICU : up to 90 days
Type of extrapulmonary infections during the hospitalization in the ICU
Measured: during stay in the ICU : up to 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2015 (estimated)
- Study start3 Jun 2016
- Primary completion16 Aug 2018
- Study completion16 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (37)Papers the sponsor has linked to this study.
- Other trials for Ventilator-Associated PneumoniaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 190 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Adrien Bouglé, MD, Principal investigator, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02634411
- Sponsor's protocol ID
- P 140923
- Other IDs
- AOM 14515, IDRCB n°: 2015-A00375-44
- Acronym
- iDIAPASON
- Status last verified
- Oct 2021
- First submitted
- 19 Nov 2015
- Last updated
- 20 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Gaynes R, Edwards JR; National Nosocomial Infections Surveillance System. Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis. 2005 Sep 15;41(6):848-54. doi: 10.1086/432803. Epub 2005 Aug 16.
PubMed 16107985Neuhauser MM, Weinstein RA, Rydman R, Danziger LH, Karam G, Quinn JP. Antibiotic resistance among gram-negative bacilli in US intensive care units: implications for fluoroquinolone use. JAMA. 2003 Feb 19;289(7):885-8. doi: 10.1001/jama.289.7.885.
PubMed 12588273Crouch Brewer S, Wunderink RG, Jones CB, Leeper KV Jr. Ventilator-associated pneumonia due to Pseudomonas aeruginosa. Chest. 1996 Apr;109(4):1019-29. doi: 10.1378/chest.109.4.1019.
PubMed 8635325Trouillet JL, Vuagnat A, Combes A, Kassis N, Chastre J, Gibert C. Pseudomonas aeruginosa ventilator-associated pneumonia: comparison of episodes due to piperacillin-resistant versus piperacillin-susceptible organisms. Clin Infect Dis. 2002 Apr 15;34(8):1047-54. doi: 10.1086/339488. Epub 2002 Mar 15.
PubMed 11914992Garnacho-Montero J, Sa-Borges M, Sole-Violan J, Barcenilla F, Escoresca-Ortega A, Ochoa M, Cayuela A, Rello J. Optimal management therapy for Pseudomonas aeruginosa ventilator-associated pneumonia: an observational, multicenter study comparing monotherapy with combination antibiotic therapy. Crit Care Med. 2007 Aug;35(8):1888-95. doi: 10.1097/01.CCM.0000275389.31974.22.
PubMed 17581492Planquette B, Timsit JF, Misset BY, Schwebel C, Azoulay E, Adrie C, Vesin A, Jamali S, Zahar JR, Allaouchiche B, Souweine B, Darmon M, Dumenil AS, Goldgran-Toledano D, Mourvillier BH, Bedos JP; OUTCOMEREA Study Group. Pseudomonas aeruginosa ventilator-associated pneumonia. predictive factors of treatment failure. Am J Respir Crit Care Med. 2013 Jul 1;188(1):69-76. doi: 10.1164/rccm.201210-1897OC.
PubMed 23641973Chastre J, Wolff M, Fagon JY, Chevret S, Thomas F, Wermert D, Clementi E, Gonzalez J, Jusserand D, Asfar P, Perrin D, Fieux F, Aubas S; PneumA Trial Group. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003 Nov 19;290(19):2588-98. doi: 10.1001/jama.290.19.2588.
PubMed 14625336Klompas M. Does this patient have ventilator-associated pneumonia? JAMA. 2007 Apr 11;297(14):1583-93. doi: 10.1001/jama.297.14.1583.
PubMed 17426278Pugin J, Auckenthaler R, Mili N, Janssens JP, Lew PD, Suter PM. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic "blind" bronchoalveolar lavage fluid. Am Rev Respir Dis. 1991 May;143(5 Pt 1):1121-9. doi: 10.1164/ajrccm/143.5_Pt_1.1121.
PubMed 2024824Johanson WG Jr, Pierce AK, Sanford JP, Thomas GD. Nosocomial respiratory infections with gram-negative bacilli. The significance of colonization of the respiratory tract. Ann Intern Med. 1972 Nov;77(5):701-6. doi: 10.7326/0003-4819-77-5-701. No abstract available.
PubMed 5081492Baram D, Hulse G, Palmer LB. Stable patients receiving prolonged mechanical ventilation have a high alveolar burden of bacteria. Chest. 2005 Apr;127(4):1353-7. doi: 10.1378/chest.127.4.1353.
PubMed 15821215El Solh AA, Akinnusi ME, Wiener-Kronish JP, Lynch SV, Pineda LA, Szarpa K. Persistent infection with Pseudomonas aeruginosa in ventilator-associated pneumonia. Am J Respir Crit Care Med. 2008 Sep 1;178(5):513-9. doi: 10.1164/rccm.200802-239OC. Epub 2008 May 8.
PubMed 18467510Borg MA. Bed occupancy and overcrowding as determinant factors in the incidence of MRSA infections within general ward settings. J Hosp Infect. 2003 Aug;54(4):316-8. doi: 10.1016/s0195-6701(03)00153-1.
PubMed 12919764Trouillet JL, Chastre J, Vuagnat A, Joly-Guillou ML, Combaux D, Dombret MC, Gibert C. Ventilator-associated pneumonia caused by potentially drug-resistant bacteria. Am J Respir Crit Care Med. 1998 Feb;157(2):531-9. doi: 10.1164/ajrccm.157.2.9705064.
PubMed 9476869Micek ST, Ward S, Fraser VJ, Kollef MH. A randomized controlled trial of an antibiotic discontinuation policy for clinically suspected ventilator-associated pneumonia. Chest. 2004 May;125(5):1791-9. doi: 10.1378/chest.125.5.1791.
PubMed 15136392
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of the Duration of Antibiotics on Clinical Events in Patients With Pseudomonas Aeruginosa Ventilator-associated Pneumonia : a Randomized Controlled Study (iDIAPASON)
- ClinicalTrials.gov ID
- NCT02634411
- Acronym / sponsor ID
- iDIAPASON / P 140923
- Conditions
- Ventilator-Associated Pneumonia
- Keywords
- Ventilator Associated, Pneumonia, Antibiotic treatment, Pseudomonas aeruginosa
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 190 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 3 Jun 2016 (actual)
- Primary completion
- 16 Aug 2018 (actual)
- Study completion
- 16 Aug 2018 (actual)
- First posted
- 18 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Ventilator-associated pneumonia (VAP) is a major cause of morbidity and mortality in the ICU, accounting for 25% of infections in intensive care units (Réseau RAISIN 2012). From 1975 to 2003, the incidence of hospital-acquired pneumonia caused by Pseudomonas aeruginosa (PA) has almost doubled, from 9.6% to 18.1%. In a US national large-scale survey, PA was the most frequently isolated gram-negative aerobic bacterium from ICUs (23%) and also the most frequent bacterium isolated from the respiratory tract (31.6%).
PA-VAP is associated with a high mortality ranging from 40% up to 69%, and with high rates of recurrence despite adequate antimicrobial therapy. In a large randomized trial regarding the optimal duration of antibiotic therapy in overall VAPs, the rate of recurrence among the subgroup of non-fermenting Gram negative bacilli (NF-GNB) documented VAP varied between 19.0% and 32.8%, according to the randomization arm. Finally, a recently published cohort about 393 PA-VAP in 314 patients, the composite criteria failure treatment (death and recurrence) occured in 112 cases (28.5%).
Hypothesis A short duration antibiotherapy (8 days) vs. long duration antibiotherapy (15 days) in treatment of Pseudomonas aeruginosa Ventilator-Associated Pneumonia (PA-VAP) is safe and not associated with an increased mortality or recurrence rate of PA-VAP.
The demonstration of this hypothesis could lead to decrease antibiotic exposure during the hospitalization in the Intensive Care Unit (ICU) and in turn reduce the acquisition and the spread of multidrug-resistant pathogens (MDR).
Objectives
- Primary objective To assess the non-inferiority of a short duration of antibiotics (8 days) vs. prolonged antibiotic therapy (15 days) in Pseudomonas aeruginosa ventilator-associated pneumonia (PA-VAP) on morbi-mortality at 90 days.
- Secondary objectives
To compare between short and long duration of antibiotics on:
- mortality in the ICU
- morbidity in the ICU (mechanical ventilation, duration of hospitalization)
- exposure and acquisition of MDR during hospitalization
- number and types of extrapulmonary infections
Plan for the research
- Concise description of the primary and secondary assessment criteria
- Primary assessment criterion: 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)).
- Secondary assessment criteria:
- D30 and D90 mortality rate (%)
- Morbidity by: Duration of mechanical ventilation (days) Duration of hospitalization in ICU (days)
- Exposure to antibiotics during the hospitalization in the ICU (days)
- Number and types of extrapulmonary infections during the hospitalization in the ICU (n)
- Acquisition of MDR during the hospitalization in the ICU (swab sample of rectum and anterior nares)
- Description of research methodology
Randomized, open-labeled non inferiority trial comparing to parallel groups:
- 8 days of antibiotic therapy
- 15 days of antibiotic therapy
Antibiotic therapy Antibiotic treatment should be started just after realization of bacteriological sampling, without waiting for the result. The choice of initial antibiotic therapy will be left to the discretion of the physician but will be essentially based on the clinical context, previously antibiotic therapy, the presence or absence of risk factors for MDR (antibiotics or hospitalization in previous 90 days, current hospitalization ≥ 5 days, MV ≥ 5 days, supported in a dialysis center or residency in a nursing home), local epidemiological data, and finally if the patient is already known as being colonized by a MDR. Investigators would be strongly encouraged to convert this initial regimen into a narrow- spectrum therapy, based on culture results.
All antibiotics would be withdrawn, either at the end of day 8 or day 15, according to the randomization assignment, except those prescribed for a documented pulmonary infection recurrence before that day.
An algorithm for the initial prescription of antibiotics will be established in each ICU, the algorithm will be adapted whenever necessary to changes in the local ecology.
Number of centres participating 42 french Intensive Care Units (ICUs)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 8 days of effective antibiotic treatment | Experimental | Drug: 8 days of effective antibiotic treatmentAntibiotic 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. |
| 15 days of effective antibiotic treatment | Sham comparator | Drug: 15 days of effective antibiotic treatmentAntibiotic 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients older than 18 years
- Mechanical ventilation ≥ 48 hours
- Documented Pseudomonas aeruginosa ventilator-associated pneumonia:
- Written informed consent
- Patient affiliated to French social security
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 8 days of effective antibiotic treatmentAntibiotics 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. | Drug | 8 days of effective antibiotic treatment |
| 15 days of effective antibiotic treatmentAntibiotics 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. | Drug | 15 days of effective antibiotic treatment |
Primary outcome
A composite endpoint of morbi-mortality combining Day-90 mortality and PA-VAP recurrence rate during hospitalization in the ICU (within 90 days).
Time frame: 90 days after effective antibiotherapy
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)).
7 secondary outcomes
Measure of mortality rate (%) in the ICU
Time frame: Day 30 and Day 90 after effective antibiotherapy
Measure of morbidity in ICU by duration of mechanical ventilation (days)
Time frame: Day 30 and Day 90 after effective antibiotherapy
Measure of morbidity in ICU by duration of hospitalization in ICU (days)
Time frame: Day 30 and Day 90 after effective antibiotherapy
Acquisition of MDR during the hospitalization in the ICU.
Time frame: during stay in the ICU : up to 90 days
Exposure to antibiotics during the hospitalization in the ICU (days)
Time frame: during stay in the ICU : up to 90 days
Number of extrapulmonary infections during the hospitalization in the ICU
Time frame: during stay in the ICU : up to 90 days
Type of extrapulmonary infections during the hospitalization in the ICU
Time frame: during stay in the ICU : up to 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2021.
- Background: PubMed 16107985Gaynes R, Edwards JR; National Nosocomial Infections Surveillance System. Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis. 2005 Sep 15;41(6):848-54. doi: 10.1086/432803. Epub 2005 Aug 16.
- Background: PubMed 12588273Neuhauser MM, Weinstein RA, Rydman R, Danziger LH, Karam G, Quinn JP. Antibiotic resistance among gram-negative bacilli in US intensive care units: implications for fluoroquinolone use. JAMA. 2003 Feb 19;289(7):885-8. doi: 10.1001/jama.289.7.885.
- Background: PubMed 8635325Crouch Brewer S, Wunderink RG, Jones CB, Leeper KV Jr. Ventilator-associated pneumonia due to Pseudomonas aeruginosa. Chest. 1996 Apr;109(4):1019-29. doi: 10.1378/chest.109.4.1019.
- Background: PubMed 11914992Trouillet JL, Vuagnat A, Combes A, Kassis N, Chastre J, Gibert C. Pseudomonas aeruginosa ventilator-associated pneumonia: comparison of episodes due to piperacillin-resistant versus piperacillin-susceptible organisms. Clin Infect Dis. 2002 Apr 15;34(8):1047-54. doi: 10.1086/339488. Epub 2002 Mar 15.
- Background: PubMed 17581492Garnacho-Montero J, Sa-Borges M, Sole-Violan J, Barcenilla F, Escoresca-Ortega A, Ochoa M, Cayuela A, Rello J. Optimal management therapy for Pseudomonas aeruginosa ventilator-associated pneumonia: an observational, multicenter study comparing monotherapy with combination antibiotic therapy. Crit Care Med. 2007 Aug;35(8):1888-95. doi: 10.1097/01.CCM.0000275389.31974.22.
- Background: PubMed 23641973Planquette B, Timsit JF, Misset BY, Schwebel C, Azoulay E, Adrie C, Vesin A, Jamali S, Zahar JR, Allaouchiche B, Souweine B, Darmon M, Dumenil AS, Goldgran-Toledano D, Mourvillier BH, Bedos JP; OUTCOMEREA Study Group. Pseudomonas aeruginosa ventilator-associated pneumonia. predictive factors of treatment failure. Am J Respir Crit Care Med. 2013 Jul 1;188(1):69-76. doi: 10.1164/rccm.201210-1897OC.
- Background: PubMed 14625336Chastre J, Wolff M, Fagon JY, Chevret S, Thomas F, Wermert D, Clementi E, Gonzalez J, Jusserand D, Asfar P, Perrin D, Fieux F, Aubas S; PneumA Trial Group. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003 Nov 19;290(19):2588-98. doi: 10.1001/jama.290.19.2588.
- Background: PubMed 17426278Klompas M. Does this patient have ventilator-associated pneumonia? JAMA. 2007 Apr 11;297(14):1583-93. doi: 10.1001/jama.297.14.1583.
- Background: PubMed 2024824Pugin J, Auckenthaler R, Mili N, Janssens JP, Lew PD, Suter PM. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic "blind" bronchoalveolar lavage fluid. Am Rev Respir Dis. 1991 May;143(5 Pt 1):1121-9. doi: 10.1164/ajrccm/143.5_Pt_1.1121.
- Background: PubMed 5081492Johanson WG Jr, Pierce AK, Sanford JP, Thomas GD. Nosocomial respiratory infections with gram-negative bacilli. The significance of colonization of the respiratory tract. Ann Intern Med. 1972 Nov;77(5):701-6. doi: 10.7326/0003-4819-77-5-701. No abstract available.
- Background: PubMed 15821215Baram D, Hulse G, Palmer LB. Stable patients receiving prolonged mechanical ventilation have a high alveolar burden of bacteria. Chest. 2005 Apr;127(4):1353-7. doi: 10.1378/chest.127.4.1353.
- Background: PubMed 18467510El Solh AA, Akinnusi ME, Wiener-Kronish JP, Lynch SV, Pineda LA, Szarpa K. Persistent infection with Pseudomonas aeruginosa in ventilator-associated pneumonia. Am J Respir Crit Care Med. 2008 Sep 1;178(5):513-9. doi: 10.1164/rccm.200802-239OC. Epub 2008 May 8.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adrien Bouglé, MD principal investigator
APHP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 8 days of effective antibiotic treatment and 15 days of effective antibiotic treatment in people with Ventilator-Associated Pneumonia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
A composite endpoint of morbi-mortality combining Day-90 mortality and PA-VAP recurrence rate during hospitalization in the ICU (within 90 days). (time frame: 90 days after effective antibiotherapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02634411, which also lists 37 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2021; AzTrials last refreshed its copy on 8 Nov 2026.