Clinical trial NCT03452826: Combined Use of a Respiratory Broad Panel mPCR and Procalcitonin to Reduce Duration of Antibiotics Exposure in Patients With Severe Community-Acquired Pneumonia
Official title: Combined Use of a Respiratory Broad Panel MULTIplex PCR and Procalcitonin to Reduce Antibiotics Exposure in Patients With Severe Community-Acquired Pneumonia: a Multicentre, Parallel-group, Open-label, Randomized Controlled Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Community-acquired Pneumonia
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2018-03-02
Enrollment: 411
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Day 28
Secondary outcomes:
measure: Mortality at 28 (D28) and 90 days (D90);
timeFrame: Day 28 and day 90
measure: Number of defined daily dose (DDD) per 100 patient days of broad- and narrow-spectrum antibiotics
timeFrame: Day 28
measure: Antibiotics duration at D28
timeFrame: Day 28
measure: Number of organ-failure free days (based on SOFA) at D28
timeFrame: Day 28
measure: Incidence rates of bacterial superinfections at D28
timeFrame: Day 28
measure: Incidence rates of colonization/infection with multidrug resistant bacteria and Clostridium difficile infections at D28
timeFrame: Day 28
measure: Incidence rates of relapse (same pathogen) or reinfection (another pathogen) at D28
timeFrame: Day 28
measure: Duration of ICU and hospital stay
timeFrame: Day 90
measure: Cost of the total hospital admissions (including 90-day repeated admissions), ICU costs, cost of the microbiological diagnostic workup;
timeFrame: Day 90
measure: Incremental / decremental cost effectiveness ratio in cost per treatment success (90-day composite of all-cause death and infection recurrence).
timeFrame: Day 90
measure: Sensitivity, specificity, and likelihood ratios of the broad panel mPCR Film Array for the diagnosis of pneumonia, taking the conventional microbiological tests as reference
timeFrame: Day 28
measure: Euroquol questionary (EQ-5D-3L)
timeFrame: Day 90
measure: To assess the operational values of the broad panel mPCR Film Array for the diagnosis of ventilator associated pneumonia (in the intervention group only).
timeFrame: Day 28
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital BICHAT
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Jean-François TIMSIT, PU-PH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Voiriot G, Fartoukh M, Durand-Zaleski I, Berard L, Rousseau A, Armand-Lefevre L, Verdet C, Argaud L, Klouche K, Megarbane B, Patrier J, Richard JC, Reignier J, Schwebel C, Souweine B, Tandjaoui-Lambiotte Y, Simon T, Timsit JF; MULTI-CAP study group. Combined use of a broad-panel respiratory multiplex PCR and procalcitonin to reduce duration of antibiotics exposure in patients with severe community-acquired pneumonia (MULTI-CAP): a multicentre, parallel-group, open-label, individual randomised trial conducted in French intensive care units. BMJ Open. 2021 Aug 18;11(8):e048187. doi: 10.1136/bmjopen-2020-048187.
citation: Kerneis S, Visseaux B, Armand-Lefevre L, Timsit JF. Molecular diagnostic methods for pneumonia: how can they be applied in practice? Curr Opin Infect Dis. 2021 Apr 1;34(2):118-125. doi: 10.1097/QCO.0000000000000713.