Use of MULTIplex PCR, Procalcitonin, and Sputum Appearance to Reduce Duration of Antibiotic Therapy During Severe COPD EXAcerbation: A Controlled, Randomized, Open-label, Parallel-Group, Multicenter Trial

NCT05280132 | Recruiting

• 2 other identifiers: APHP2100852021-005435-23
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 1

Brief Summary

COPD is a common chronic disease. Its natural course is characterized by Acute exacerbations (AE). This may require hospitalization or even ICU/RESUSCITATION admission. The most common causes are respiratory distress with hypercapnic acidosis that requires mechanical ventilation (Invasive or non-invasive). Lower respiratory tract infections, bacteria and/or viruses are the main pathogenic factors of AE. The treatment of AECOPD is initially symptomatic treatment, combining bronchodilators, ventilatory support (oxygen therapy and/or mechanical ventilation) and respiratory physiotherapy. Systemic corticosteroid therapy is optional. When i) the sputum is purulent and ii) increased dyspnea and / or an increase in sputum volume is observed, antibiotic treatment is recommended for hospitalized patients. Antibiotic therapy is routinely recommended when mechanical ventilation is required. During ICU/RESUSCITATION AECOPD, more than 85% of patients received antibiotic therapy, with a median duration of 8 to 9 days, and the benefit of antibiotic therapy is likely to be limited to infected patients. Suspected or documented lower respiratory tract bacteria, that is, 25% to 50% of patients. This will lead to overuse of antibiotics, which is a problem for patients and the community. A personalized antibiotic strategy could limit this phenomenon, relying on multimodal methods, using aspect of sputum (clinical method), procalcitonin (PCT) (biological method) and the FilmArray ™ Pneumonia Panel extended panel multiplex respiratory PCR Plus (mPCR FA-PPP) (Biomérieux®) (microbiological approach). The hypothesis of this study is that sputum appearance, procalcitonin (PCT) and the FilmArray ™ Pneumonia Panel Plus expanded panel multiplex respiratory PCR (mPCR FA-PPP) (Biomérieux®) could be used in combination , and their results integrated into a decision-making algorithm aimed at personalizing antibiotic therapy and guiding its early termination in patients admitted to ICU/RESUSCITATION due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD) to the main benefit of antibiotic savings, and without additional risk to patient safety.

Conditions

Acute Exacerbation of COPD

Keywords

AECOPD; respiratory multiplex PCR; Appearance of sputum; Procalcitonin; Antibiotics saving; Diagnosis; Treatment

Outcome Measures

Primary Outcomes (1)

• Number of antibiotic-free days

  The number of days alive without antibiotics at Day 28.

  Day 28

Secondary Outcomes (12)

• Number of days with antibiotics in survivors at D28

  Day 28

• Number of days with broad spectrum antibiotics in survivors at D28

  Day 28

• Nosocomial pneumonia incidence rate

  Day 28

• Multidrug-resistant bacteria colonization / infection rate

  Day 28

• ICU lengths of stay

  Day 28

Study Arms (2)

Personalized strategy

EXPERIMENTAL

Personalized antibiotic treatment based on mPCR results, PCT (values and kinetics) and appearance of sputum. A broad panel respiratory mPCR FA-PPP is performed on a respiratory tract sample collected 12 hours after inclusion. After inclusion (D0), an algorithm of early antibiotic adaptation and discontinuation will be applied immediately and repeated every day until day 7. This algorithm of early antibiotic adaptation and discontinuation is based on a multimodal approach, using: * The appearance of sputum (clinical approach); * PCT values and kinetics (biological approach); * Results of mPCR FA-PPP (microbiological approach).

Procedure: Personalized antibiotic treatment

Usual strategy

OTHER

Usual antibiotic treatment Left at the discretion of the physician as in usual practice

Other: Usual antibiotic treatment

Interventions

Personalized antibiotic treatment PROCEDURE

Personalized antibiotic treatment based on mPCR results, PCT (values and kinetics) and appearance of sputum.

Personalized strategy

Usual antibiotic treatment OTHER

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

Usual strategy

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old
• COPD (according to GOLD 2020), whatever the stage (I-IV)
• Acute exacerbation (defined as the onset or worsening of one or more of the usual signs/symptoms of COPD) with acute worsening of respiratory symptoms that result in additional therapy) with acute respiratory failure requiring admission to ICU and ventilatory support (invasive mechanical ventilation or non-invasive mechanical ventilation or high-flow nasal oxygen therapy with FiO2 ≥ 50%)
• Affiliation to a social security

You may not qualify if:

• The interval between admission to the hospital and admission to ICU more than 3 days
• Antibiotic therapy clearly needed for a suspected or documented extra-respiratory infection
• Congenital or acquired immunosuppression (congenital immune deficiency, high-grade hematologic malignancies, use of immunosuppressive drugs in the last 30 days including anti-cancer chemotherapy and antirejection medications, corticosteroid treatment ≥ 20 mg/d prednisone equivalent for at least 14 days, neutropenia, HIV with unknown or known CD4 \<200 / µL in the past 6 months)
• Tracheotomy
• Bronchiectasis / cystic fibrosis
• Moribund patient (imminent death)
• Patient deprived of liberty and / or under legal protection measure
• Patient already included in MULTI-EXA
• Patient already included in a type 1 interventional study on antibiotics
• Ongoing pregnancy

Sponsors & Collaborators

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

Study Sites (1)

Intensive care department-Hospital Tenon

Paris, 75020, France

RECRUITING

MeSH Terms

Conditions

Disease

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Guillaume VOIRIOT, Professor

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guillaume VOIRIOT, Professor

CONTACT

01 56 01 62 63; guillaume.voiriot@aphp.fr

Muriel Fartoukh, PU-PH

CONTACT

01 56 01 65 72; muriel.fartoukh@aphp.fr

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: March 4, 2022
• First Posted: March 15, 2022
• Study Start: December 8, 2022
• Primary Completion: April 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: June 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

FR (1)