Community-acquired Pneumonia
Conditions
Brief summary
To assess the effectiveness of a management strategy combining a broad panel respiratory mPCR and an algorithm of early antibiotic de-escalation and discontinuation based on both the mPCR results and the procalcitonin (intervention) in severe CAP, as compared to a conventional strategy (control). A multicentre, parallel-group, open-label, randomized controlled trial. The primary assessment criterion est the number of antibiotic-free days at 28 days
Detailed description
Randomization is performed immediately after the inclusion. * In the intervention arm, a broad panel respiratory mPCR is performed on a lower respiratory tract sample (bronchoalveolar lavage fluid or tracheal aspirate, otherwise sputum), collected before the 12th hour following inclusion. * In both arms, an additional lower respiratory tract sample (bronchoalveolar lavage fluid or tracheal aspirate, otherwise sputum) is collected for biological studies and banking. * In the intervention arm, an algorithm of early antibiotic de-escalation and discontinuation is based on the early microbiological results, including the mPCR results, and the procalcitonin value. This algorithm is applied as soon as possible (before the 24th hour following inclusion if possible). * In the control arm, initial antibiotic therapy is maintained, according to guidelines. * In both arms, after 72 hours of antibiotic therapy, ICU physicians are advised to use procalcitonin (values and kinetics) to guide antibiotic therapy discontinuation, with a recommended total duration of 7 days, unless otherwise indicated. * In both arms, a switch to oral therapy is encouraged
Interventions
DEVICEAntibiotic therapy according to the result of mPCR (device)
* Phone call at D28 and D90, unless the patient is still hospitalized; * Collection of a respiratory tract sample (either distal, i.e. tracheal aspirate or bronchoalveolar lavage, or proximal, i.e. sputum) for broad panel respiratory mPCR in the intervention arm. * Collection of an additional respiratory tract sample for biological banking in both arms.
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults (≥18 years) with CAP admitted to the ICU since 18 hours or less; the diagnosis of pneumonia includes two clinical criteria among a temperature \> 37.8°C, tachypnea (respiratory rate \> 25/min), chest pain, cough, expectoration, localized crackles, with or without signs of pleural effusion, pulse oximetry less than 92% while breathing room air, and a newly-appeared parenchymal infiltrate; the pneumonia is community-acquired if the time between hospital admission and ICU referral is below or equal to 48 hours. * Informed consent or emergency procedure.
Exclusion criteria
* Pregnancy; * Congenital immunodeficiency; * HIV infection with the lymphocyte CD4 count below 200/mm3 or unknown in the last year; * Acute hematologic malignancy; * Neutropenia (\<1 leucocyte/mL or \< 0.5 neutrophil/mL); * Immunosuppressive drugs within the previous 30 days, including anti-cancer chemotherapy and anti-rejection drugs for organ/bone marrow transplant * Corticosteroids ≥ 20 mg/d of prednisone equivalent for more than 14 days; * chronic obstructive pulmonary disease (COPD) with previous history of colonization/infection with Pseudomonas aeruginosa; * Tracheostomy; * Diffuse bronchiectasis, cystic fibrosis; * Aspiration pneumonia; * Moribund patient or death expected from underlying disease during the current admission; * Patient deprived of liberty or under legal protection measure; * Participation in another interventional trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The effectiveness of a management combining a broad panel respiratory mPCR and an algorithm of early antibiotic de-escalation and discontinuation based on both the mPCR results and the procalcitonin in severe CAP, as compared to a conventional strategy | Day 28 | the number of antibiotic free days at D28, which corresponds to the number of days alive without any at Day 28. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality at 28 (D28) and 90 days (D90); | Day 28 and day 90 | Mortality rate at D28 and D90 |
| Number of defined daily dose (DDD) per 100 patient days of broad- and narrow-spectrum antibiotics | Day 28 | Number of defined daily dose (DDD) per 100 patient days of broad- and narrow-spectrum antibiotics |
| Antibiotics duration at D28 | Day 28 | Antibiotics duration at D28 |
| Number of organ-failure free days (based on SOFA) at D28 | Day 28 | Number of organ-failure free days (based on SOFA) at D28 |
| Incidence rates of bacterial superinfections at D28 | Day 28 | Incidence rates of bacterial superinfections at D28 |
| Incidence rates of colonization/infection with multidrug resistant bacteria and Clostridium difficile infections at D28 | Day 28 | Incidence rates of colonization/infection with multidrug resistant bacteria and Clostridium difficile infections at D28 |
| Incidence rates of relapse (same pathogen) or reinfection (another pathogen) at D28 | Day 28 | Incidence rates of relapse (same pathogen) or reinfection (another pathogen) at D28 |
| Duration of ICU and hospital stay | Day 90 | Duration of ICU and hospital stay |
| Cost of the total hospital admissions (including 90-day repeated admissions), ICU costs, cost of the microbiological diagnostic workup; | Day 90 | Cost of the total hospital admissions (including 90-day repeated admissions), ICU costs, cost of the microbiological diagnostic workup; |
| Incremental / decremental cost effectiveness ratio in cost per treatment success (90-day composite of all-cause death and infection recurrence). | Day 90 | Incremental / decremental cost effectiveness ratio in cost per treatment success (90-day composite of all-cause death and infection recurrence). |
| Sensitivity, specificity, and likelihood ratios of the broad panel mPCR Film Array for the diagnosis of pneumonia, taking the conventional microbiological tests as reference | Day 28 | Sensitivity, specificity, and likelihood ratios of the broad panel mPCR Film Array for the diagnosis of pneumonia, taking the conventional microbiological tests as reference |
| Euroquol questionary (EQ-5D-3L) | Day 90 | Euroquol questionary (EQ-5D-3L) |
| To assess the operational values of the broad panel mPCR Film Array for the diagnosis of ventilator associated pneumonia (in the intervention group only). | Day 28 | Sensitivity, specificity, and likelihood ratios of the broad panel mPCR Film Array for the diagnosis of ventilator associated pneumonia (in the intervention group only), taking the conventional microbiological tests as reference. |
Countries
France
Outcome results
None listed