Use of a Respiratory Multiplex PCR and Procalcitonin to Reduce Antibiotics Exposure in Patients With Severe Confirmed COVID-19 Pneumonia

NCT ID: NCT04334850

Last Updated: 2021-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 194 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-04-20
• Study Completion Date: 2021-06-23

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.

Conditions

Covid19; Pneumonia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Targeted antibiotic treatment according to the results of mPCR

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.

Group Type: EXPERIMENTAL

Combined use of a respiratory broad panel multiplex PCR and procalcitonin

Intervention Type: PROCEDURE

The actions or procedures added by the research are the application of the algorithm of early antibiotics de-escalation and discontinuation.

Control arm

The antimicrobial therapy is left at the discretion of the physicians, as in usual practice.

Group Type: OTHER

Usual antibiotic treatment

Intervention Type: OTHER

The antimicrobial therapy is left at the discretion of the physicians, as in usual practice.

Interventions

Combined use of a respiratory broad panel multiplex PCR and procalcitonin

The actions or procedures added by the research are the application of the algorithm of early antibiotics de-escalation and discontinuation.

Intervention Type: PROCEDURE

Usual antibiotic treatment

The antimicrobial therapy is left at the discretion of the physicians, as in usual practice.

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioMérieux

INDUSTRY

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Muriel FARTOUKH, PU-PH MD PHD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Intensive care department-Hospital Tenon

Paris, , France

Countries

France

Other Identifiers

2020-001324-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

APHP200392

Identifier Type: -

Identifier Source: org_study_id