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Combined Use of a Respiratory Broad Panel mPCR and Procalcitonin to Reduce Duration of Antibiotics Exposure in Patients With Severe Community-Acquired Pneumonia (MULTI-CAP)

Primary Purpose

Community-acquired Pneumonia

Status

Completed

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

Antibiotic therapy according to the result of mPCR (device)

About this trial

This is an interventional other trial for Community-acquired Pneumonia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Hôpital BICHAT

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Antibiotic therapy according to the result of mPCR

Antibiotic therapy at discretion of ICU physicians

Arm Description

Combined use of a respiratory broad panel Multiplex polymerase chain reaction (mPCR) (performed on a lower respiratory tract sample : bronchoalveolar lavage fluid or tracheal aspirate, otherwise sputum) and procalcitonin.

Antibiotic therapy at discretion of ICU physicians

Outcomes

Primary Outcome Measures

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

the number of antibiotic free days at D28, which corresponds to the number of days alive without any at Day 28.

Secondary Outcome Measures

Mortality at 28 (D28) and 90 days (D90);

Mortality rate at D28 and D90

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

Antibiotics duration at D28

Number of organ-failure free days (based on SOFA) at D28

Incidence rates of bacterial superinfections at D28

Incidence rates of colonization/infection with multidrug resistant bacteria and Clostridium difficile infections at D28

Incidence rates of relapse (same pathogen) or reinfection (another pathogen) at D28

Duration of ICU and hospital stay

Cost of the total hospital admissions (including 90-day repeated admissions), ICU costs, cost of the microbiological diagnostic workup;

Incremental / decremental cost effectiveness ratio in cost per treatment success (90-day composite of all-cause death and infection recurrence).

Sensitivity, specificity, and likelihood ratios of the broad panel mPCR Film Array for the diagnosis of pneumonia, taking the conventional microbiological tests as reference

Euroquol questionary (EQ-5D-3L)

To assess the operational values of the broad panel mPCR Film Array for the diagnosis of ventilator associated pneumonia (in the intervention group only).

Sensitivity, specificity, and likelihood ratios of the broad panel mPCR Film Array for the diagnosis of ventilator associated pneumonia (in the intervention group only), taking the conventional microbiological tests as reference.

Full Information

NCT ID

NCT03452826

First Posted

February 26, 2018

Last Updated

October 17, 2023

Sponsor

Assistance Publique - Hôpitaux de Paris

1. Study Identification

Unique Protocol Identification Number

NCT03452826

Brief Title

Combined Use of a Respiratory Broad Panel mPCR and Procalcitonin to Reduce Duration of Antibiotics Exposure in Patients With Severe Community-Acquired Pneumonia

Acronym

MULTI-CAP

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

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Completed

Study Start Date

October 4, 2018 (Actual)

Primary Completion Date

August 5, 2022 (Actual)

Study Completion Date

March 1, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Community-acquired Pneumonia

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

411 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Antibiotic therapy according to the result of mPCR

Arm Type

Experimental

Arm Description

Arm Title

Antibiotic therapy at discretion of ICU physicians

Arm Type

No Intervention

Arm Description

Antibiotic therapy at discretion of ICU physicians

Intervention Type

Device

Intervention Name(s)

Antibiotic therapy according to the result of mPCR (device)

Other Intervention Name(s)

Antibiotic therapy to be adapted according to the result of mPCR (device)

Intervention Description

Phone call at D28 and D90, unless the patient is still hospitalized; Collection of a respiratory tract sample (either distal, i.e. tracheal aspirate or bronchoalveolar lavage, or proximal, i.e. sputum) for broad panel respiratory mPCR in the intervention arm. Collection of an additional respiratory tract sample for biological banking in both arms.

Primary Outcome Measure Information:

Title

Description

the number of antibiotic free days at D28, which corresponds to the number of days alive without any at Day 28.

Time Frame

Day 28

Secondary Outcome Measure Information:

Title

Mortality at 28 (D28) and 90 days (D90);

Description

Mortality rate at D28 and D90

Time Frame

Day 28 and day 90

Title

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

Description

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

Time Frame

Day 28

Title

Antibiotics duration at D28

Description

Antibiotics duration at D28

Time Frame

Day 28

Title

Number of organ-failure free days (based on SOFA) at D28

Description

Number of organ-failure free days (based on SOFA) at D28

Time Frame

Day 28

Title

Incidence rates of bacterial superinfections at D28

Description

Incidence rates of bacterial superinfections at D28

Time Frame

Day 28

Title

Incidence rates of colonization/infection with multidrug resistant bacteria and Clostridium difficile infections at D28

Description

Incidence rates of colonization/infection with multidrug resistant bacteria and Clostridium difficile infections at D28

Time Frame

Day 28

Title

Incidence rates of relapse (same pathogen) or reinfection (another pathogen) at D28

Description

Incidence rates of relapse (same pathogen) or reinfection (another pathogen) at D28

Time Frame

Day 28

Title

Duration of ICU and hospital stay

Description

Duration of ICU and hospital stay

Time Frame

Day 90

Title

Cost of the total hospital admissions (including 90-day repeated admissions), ICU costs, cost of the microbiological diagnostic workup;

Description

Cost of the total hospital admissions (including 90-day repeated admissions), ICU costs, cost of the microbiological diagnostic workup;

Time Frame

Day 90

Title

Incremental / decremental cost effectiveness ratio in cost per treatment success (90-day composite of all-cause death and infection recurrence).

Description

Incremental / decremental cost effectiveness ratio in cost per treatment success (90-day composite of all-cause death and infection recurrence).

Time Frame

Day 90

Title

Sensitivity, specificity, and likelihood ratios of the broad panel mPCR Film Array for the diagnosis of pneumonia, taking the conventional microbiological tests as reference

Description

Sensitivity, specificity, and likelihood ratios of the broad panel mPCR Film Array for the diagnosis of pneumonia, taking the conventional microbiological tests as reference

Time Frame

Day 28

Title

Euroquol questionary (EQ-5D-3L)

Description

Euroquol questionary (EQ-5D-3L)

Time Frame

Day 90

Title

To assess the operational values of the broad panel mPCR Film Array for the diagnosis of ventilator associated pneumonia (in the intervention group only).

Description

Time Frame

Day 28

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jean-François TIMSIT, PU-PH

Organizational Affiliation

Assistance Publique - Hôpitaux de Paris

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hôpital BICHAT

City

Paris

ZIP/Postal Code

75018

Country

France

12. IPD Sharing Statement

Citations:

PubMed Identifier

34408046

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.

Results Reference

derived

PubMed Identifier

33395094

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.

Results Reference

derived

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Combined Use of a Respiratory Broad Panel mPCR and Procalcitonin to Reduce Duration of Antibiotics Exposure in Patients With Severe Community-Acquired Pneumonia

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