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

NCT04334850 | Completed

• 2 other identifiers: APHP2003922020-001324-33
• Study Type: interventional
• Target: 194
• Locations: 1 country
• Sites: 1

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.

Conditions

Covid19; Pneumonia

Keywords

COVID-19 pneumonia; respiratory multiplex PCR; Procalcitonin; Antibiotics saving; Diagnosis; Treatment

Outcome Measures

Primary Outcomes (1)

• Number of antibiotic free days

  the number of days alive without any antibiotics at Day 28. The D28 time point is usual in studies assessing antibiotics saving in ICU patients.

  Day 28

Secondary Outcomes (8)

• Mortality rates

  Day 28 and Day 90

• Number of defined daily dose (DDD) per 100 patient-days of broad- and narrow-spectrum antibiotics.

  day 28

• Antibiotics duration at D28

  Day 28

• Number of organ-failure free days (based on SOFA)

  Day 28

• Incidence rates of bacterial super-infections

  day 28

Study Arms (2)

Targeted antibiotic treatment according to the results of mPCR

EXPERIMENTAL

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.

Procedure: Combined use of a respiratory broad panel multiplex PCR and procalcitonin

Control arm

OTHER

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

Other: Usual antibiotic treatment

Interventions

Combined use of a respiratory broad panel multiplex PCR and procalcitonin PROCEDURE

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

Targeted antibiotic treatment according to the results of mPCR

Usual antibiotic treatment OTHER

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

Control arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• BioMérieux: collaborator

Study Sites (1)

Intensive care department-Hospital Tenon

Paris, 75020, France

Location

MeSH Terms

Conditions

COVID-19; Pneumonia; Disease

Interventions

Procalcitonin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Calcitonin; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Protein Precursors; Proteins

Study Officials

• Muriel FARTOUKH, PU-PH MD PHD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2020
• First Posted: April 6, 2020
• Study Start: April 20, 2020
• Primary Completion: December 20, 2020
• Study Completion: June 23, 2021
• Last Updated: August 3, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)