Clinical trial NCT04334850: Use of a Respiratory Multiplex PCR and Procalcitonin to Reduce Antibiotics Exposure in Patients With Severe Confirmed COVID-19 Pneumonia
Official title: Use of a Respiratory Multiplex PCR and Procalcitonin to Reduce Antibiotics Exposure in Patients With Severe Confirmed COVID-19 Pneumonia : a Multicenter, Parallel-group, Open-label, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Covid19
Pneumonia
Keywords: COVID-19 pneumonia
respiratory multiplex PCR
Procalcitonin
Antibiotics saving
Diagnosis
Treatment
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: BioMérieux
First posted: 2020-04-06
Enrollment: 194
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The novel coronavirus SARS-CoV-2 (COVID-19) is an emerging respiratory virus that causes pneumonia. WHO data reported admission to the intensive care unit (ICU) for 6% of patients, with a mortality rate reaching 45%. To date, apart from therapeutic trials, ICU management is symptomatic, based on organ failure support therapies. In the initial phase, the therapeutic management also includes empiric antimicrobial therapy (90% of patients, in accordance with LRTI guidelines (ATS 2019) and SRLF Guidelines (2020). One challenge for the ICU physicians is the timing for discontinuation of antimicrobial treatment, especially in case of shock or ARDS, considering that a substantial proportion of COVID-19 pneumonia patients may have pulmonary bacterial coinfection/superinfection. In order to avoid unnecessary prolonged antimicrobial therapy, and subsequent selective pressure, two tests could be combined in a personalized antibiotic strategy:

* Procalcitonin (PCT): PCT is a useful tool to guide antibiotics discontinuation in community-acquired pneumonia) and viral pneumonia (PMID24612487).
* Respiratory multiplex PCR FA-PPP (Biomérieux®): panel has been enlarged, including 8 viruses and 18 bacteria (quantitative analysis). The turnaround time is short. Sensitivity is high (99%, PMID32179139). It may contribute, in combination with conventional tests, to accelerate and improve the microbiological diagnosis during severe COVID-19 pneumonia.

The hypothesize of the study is that the combination of the mPCR FA-PPP and PCT could be used to reduce antibiotics exposure in patients with severe confirmed COVID-19 pneumonia, with a higher clinical efficacy and safety as compared with a conventional strategy.

Detailed description: Inclusion (D0_H0) is performed in ICU as soon as possible, once the diagnosis of COVID-19 pneumonia is confirmed. Therefore, inclusion might be performed either on ICU admission (if the COVID-19 pneumonia has been confirmed in the pre-ICU wards) or during the ICU stay (if the COVID-19 pneumonia was confirmed after ICU admission). Conventional microbiological investigations are left at the discretion of the physicians, and may include blood cultures, Streptococcus pneumoniae and Legionella pneumophila urinary antigen assays, and a respiratory tract sample for Gram stain examination and 2 days-long culture (if not already done in the past 24 hours). Usual biology includes procalcitonin measurement. Empirical antimicrobial therapy combines a third-generation cephalosporin and a macrolide, or broader-spectrum antibiotics if risk factors for resistant bacteria are identified.

Randomization is performed immediately after the inclusion.

* In the intervention arm, a broad panel respiratory Mpcr FA-PPP is performed on respiratory tract sample (tracheal aspirate, BAL or sputum), collected 12 hours after inclusion. An algorithm of early antibiotic adaptation and discontinuation, based on the microbiological results, including the mPCR FA-PPP results, and the procalcitonin values and kinetics will be used. This algorithm will be applied as soon as possible after inclusion, and repeated day after day until D7.
* In the control arm, the antimicrobial therapy is left at the discretion of the physicians, as in usual practice.

Evaluation criteria are collected at hospital discharge or at D28, and D90. The vital status may be obtained by phone call at D28 (if the patient has been discharged before D28) and at D90.

Eligibility criteria: Inclusion Criteria:

* Adults (\>= 18 years) admitted to the ICU;
* Severe confirmed COVID-19 pneumonia, defined by i) a newly-appeared pulmonary parenchymal infiltrate; and ii) a positive RT-PCR (either upper or lower respiratory tract) for COVID-19 (SARS-CoV-2); iii) and admission to the ICU or intermediate care unit;
* Informed consent or emergency procedure.

Exclusion Criteria:

* Pregnancy ;
* Congenital immunodeficiency;
* HIV infection with CD4 count below 200/mm3 or unknown in the last year;
* High-grade hematological malignancy;
* Neutropenia (\<1 leucocyte/mL or \< 0.5 neutrophil/mL);
* Immunosuppressive drugs within the previous 30 days, including anti-cancer cytotoxic chemotherapy and anti-rejection drugs for organ/bone marrow transplant;
* Moribund patient or death expected from underlying disease during the current admission;
* Patient deprived of liberty or under legal protection measure

Primary outcomes:
measure: Number of antibiotic free days
timeFrame: Day 28
Secondary outcomes:
measure: Mortality rates
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)
timeFrame: Day 28
measure: Incidence rates of bacterial super-infections
timeFrame: day 28
measure: Incidence rates of colonization/infection with multidrug resistant bacteria and Clostridium difficile infections
timeFrame: Day 28
measure: ICU and hospital lengths of stay
timeFrame: Day 28
measure: Quality of life Quality of life
timeFrame: Day 90
Other outcomes:
Locations:
city: Paris
country: France
facility: Intensive care department-Hospital Tenon
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Muriel FARTOUKH, PU-PH MD PHD
role: PRINCIPAL_INVESTIGATOR
References: