Covid19MultiCovNCT04334850
Use of a Respiratory Multiplex PCR and Procalcitonin to Reduce Antibiotics Exposure in Patients With Severe Confirmed COVID-19 Pneumonia
A study testing Combined use of a respiratory broad panel multiplex PCR and procalcitonin and Usual antibiotic treatment in people with Covid19 and Pneumonia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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%. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Combined use of a respiratory broad panel multiplex PCR and procalcitonin and Usual antibiotic treatment
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 194 participants
- Where
- 1 siteFrance
- Study dates
- 20 Apr 2020to 23 Jun 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Being tested
- Combined use of a respiratory broad panel multiplex PCR and procalcitonin, Usual antibiotic treatment
- Keywords
- COVID-19 pneumonia, respiratory multiplex PCR, Procalcitonin, Antibiotics saving, Diagnosis, Treatment
- Medical subject headings
- COVID-19, Pneumonia, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combined use of a respiratory broad panel multiplex PCR and procalcitoninProcedure or surgery
The actions or procedures added by the research are the application of the algorithm of early antibiotics de-escalation and discontinuation.
Usual antibiotic treatmentOther
The antimicrobial therapy is left at the discretion of the physicians, as in usual practice.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Usual antibiotic treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 28
Secondary outcomes (8)
Mortality rates
Measured: Day 28 and Day 90
Number of defined daily dose (DDD) per 100 patient-days of broad- and narrow-spectrum antibiotics.
Measured: day 28
Antibiotics duration at D28
Total exposure to antibiotics
Measured: Day 28
Number of organ-failure free days (based on SOFA)
Measured: Day 28
Incidence rates of bacterial super-infections
Measured: day 28
Incidence rates of colonization/infection with multidrug resistant bacteria and Clostridium difficile infections
Measured: Day 28
ICU and hospital lengths of stay
Measured: Day 28
Quality of life Quality of life
using a quality of life questionnaire (EQ5D5L)
Measured: Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2020
- Study start20 Apr 2020
- Primary completion20 Dec 2020
- Study completion23 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid19Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 194 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- BioMérieux
- Responsible party
- Sponsor
- Investigators
- Muriel FARTOUKH, PU-PH MD PHD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04334850
- Sponsor's protocol ID
- APHP200392
- Other IDs
- 2020-001324-33
- Acronym
- MultiCov
- Status last verified
- Jul 2021
- First submitted
- 2 Apr 2020
- Last updated
- 3 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04334850
- Acronym / sponsor ID
- MultiCov / APHP200392
- Keywords
- COVID-19 pneumonia, respiratory multiplex PCR, Procalcitonin, Antibiotics saving, Diagnosis, Treatment
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 194 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- BioMérieux
- Study start
- 20 Apr 2020 (actual)
- Primary completion
- 20 Dec 2020 (actual)
- Study completion
- 23 Jun 2021 (actual)
- First posted
- 6 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Targeted antibiotic treatment according to the results of mPCR | Experimental | Procedure: Combined use of a respiratory broad panel multiplex PCR and procalcitonina 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. |
| Control arm | Other | Other: Usual antibiotic treatmentThe antimicrobial therapy is left at the discretion of the physicians, as in usual practice. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (8 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Combined use of a respiratory broad panel multiplex PCR and procalcitoninThe actions or procedures added by the research are the application of the algorithm of early antibiotics de-escalation and discontinuation. | Procedure or surgery | Targeted antibiotic treatment according to the results of mPCR |
| Usual antibiotic treatmentThe antimicrobial therapy is left at the discretion of the physicians, as in usual practice. | Other | Control arm |
Primary outcome
Number of antibiotic free days
Time frame: Day 28
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.
8 secondary outcomes
Mortality rates
Time frame: Day 28 and Day 90
Number of defined daily dose (DDD) per 100 patient-days of broad- and narrow-spectrum antibiotics.
Time frame: day 28
Antibiotics duration at D28
Time frame: Day 28
Number of organ-failure free days (based on SOFA)
Time frame: Day 28
Incidence rates of bacterial super-infections
Time frame: day 28
Incidence rates of colonization/infection with multidrug resistant bacteria and Clostridium difficile infections
Time frame: Day 28
ICU and hospital lengths of stay
Time frame: Day 28
Quality of life Quality of life
Time frame: Day 90
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Muriel FARTOUKH, PU-PH MD PHD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Combined use of a respiratory broad panel multiplex PCR and procalcitonin and Usual antibiotic treatment in people with Covid19 and Pneumonia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of antibiotic free days (time frame: Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2021.