Personalized Optimization of Antibiotic Therapy in Pulmonary Sepsis Critically Ill Patients Through Application of Rapid Microbiological Diagnostic Technologies and Pharmacokinetic/Pharmacodynamic Modelling

NCT06956053 | Not Yet Recruiting

• 1 other identifier: APHP180673
• Study Type: interventional
• Target: 658
• Locations: 0 countries
• Sites: N/A

Brief Summary

Severe community-acquired and nosocomial pneumonia are associated with substantial morbidity and mortality. Early and appropriate antimicrobial therapy (AAT) is consistently the most effective intervention for reducing mortality. Cure is most likely when pharmacokinetic (PK) / pharmacodynamics (PD) targets associated with maximum antibiotic (ABX) activity are achieved. However, the process of optimizing antibiotic therapy for critically ill patients remains a complicated challenge. A key issue is pathogen identification (ID) with subsequent antibiotic susceptibility testing (AST) results which allow for selection of AAT. Standard laboratory procedures typically require 2-3 days to provide ID and AST results. Optimal ABX dosing/dosing intervals depend in large part on PK properties in individual patients, and antibacterial effects on the infecting bacteria (PD). Alterations in the primary PK parameters, namely volume of distribution (Vd) and clearance (CL), are commonly observed, and are the most influential parameters in determining ABX dosing and exposure. ABX dosing/dosing intervals that do not account for these features are likely to lead to suboptimal ABX exposure and therapeutic failures. Because of 48-72-hours delays in ID/AST, initial treatment is frequently inappropriate in coverage, unnecessarily broad in spectrum, and/or suboptimal in dosing. Methods for rapid bacterial growth, ID, AST and minimum inhibitory concentration (MIC) identification were developed and are capable of quantitative ID in 1-2 hours and major AST in 6-8 hours using clinical specimens. Rapid ID of the infecting pathogen and its individual AST could significantly impact the early selection of AAT and, combined with therapeutic drug monitoring data, could be used to calculate optimized dosing regimens that are personalized for the patient in order to achieve appropriate PK/PD targets. Hypothesis: Application of these rapid ID/AST systems, together with prospective PK/PD monitoring of antibiotic plasma concentrations, will significantly shorten time from "sample to answer" for pathogen ID/AST, enhance personalized prescribing of antibiotics, optimize the time to targeted effective and AAT, and result in decreased treatment failure.

Conditions

Pulmonary Sepsis

Keywords

Pulmonary sepsis

Outcome Measures

Primary Outcomes (1)

• Rate of treatment failure

  It includes treatment failure that occurred early (≤72 hours) or late (\>72 hours), or at both times.

  Up to 10 days after inclusion

Secondary Outcomes (21)

• Time to availability of pathogen

  Up to 180 days

• Time to achieve targeted optimized therapy

  Up to 180 days

• Time to antibiotic switches

  Up to 180 days

• Number of started, stopped, added or adjusted (escalation or de-escalation) antibiotics

  Up to 180 days

• Time to Aantibiotic dose adjustments to achieve PK/PD targets

  Up to 180 days

Study Arms (2)

Rapid ID/AST method

EXPERIMENTAL

Diagnostic Test: Rapid ID/AST method

Conventional microbiological methods

ACTIVE COMPARATOR

Diagnostic Test: Conventional biological methods

Interventions

Rapid ID/AST method DIAGNOSTIC_TEST

1. BioFire® Film Array® Blood Culture Identification 2 BCID2 panel, bioMérieux/BioFire Diagnostics, CE marked (FDA cleared) 2. BioFire® FilmArray® Pneumonia Panels, CE marked (FDA cleared) 3. SPECIFIC REVEAL® Rapid Antimicrobial Susceptibility test (AST) System, bioMérieux/Specific Diagnostics, CE-IVD and -IVDR marked

Rapid ID/AST method

Conventional biological methods DIAGNOSTIC_TEST

Usual care

Conventional microbiological methods

Eligibility Criteria

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

You may qualify if:

• Patients hospitalized in ICU
• years of age or older
• With a pulmonary sepsis defined a s documented or suspected acute pulmonary infection (nosocomial and community-acquired pneumonia) and a SOFA score \>2.

You may not qualify if:

• COVID-19 patients
• Severe anaphylactic beta-lactam allergy
• First measurements of prescribed antibiotic concentration (TDM) not possible within 24 hr after randomization
• Pregnancy or lactation
• Any decision of limitation of care
• Pre-existing medical condition with a life expectancy of less than 3 months
• Absence of affiliation to social security
• Patient under guardianship, curatorship and deprived of liberty

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Central Study Contacts

Pierre Moine, MD PhD

CONTACT

1 47 10 77 82; pierre.moine@aphp.fr

Jérôme Lambert, MD PhD

CONTACT

1 42 49 97 42; jerome.lambert@u-paris.fr

Study Design

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

Study Record Dates

• First Submitted: April 25, 2025
• First Posted: May 2, 2025
• Study Start: May 30, 2025
• Primary Completion (Estimated): May 30, 2028
• Study Completion (Estimated): November 30, 2028
• Last Updated: May 2, 2025

Record last verified: 2025-04