Impact of BioFire FilmArray Pneumonia Panel vs Routine Diagnostics on Antimicrobial Outcomes (DOOR-MAT)

Official title

A Randomized Multicenter Clinical Trial Comparing BIOFIRE® FILMARRAY® Pneumonia (PN) Panels Versus Routine Diagnostic Methods in Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR MAT) in Hospitalized Patients With Lower Respiratory Tract Infections.

Overview

Multidrug-resistant bacterial infections are a growing global health concern. Hospital-acquired pneumonia is one of the most common infections occurring during hospitalization and can be associated with high mortality, reaching up to 50% in severe cases. One of the main reasons for poor outcomes is the delay in starting the most appropriate antibiotic treatment. Standard laboratory methods used to identify the bacteria and determine which antibiotics are effective usually take between 48 and 96 hours to provide results. During this time, patients often receive broad-spectrum antibiotics, which may not be optimal and can contribute to antimicrobial resistance. Rapid diagnostic tests, such as the BIOFIRE® FILMARRAY® Pneumonia Panel, can detect multiple bacteria and important resistance markers directly from respiratory samples in about one hour. These tests are already approved for use in Brazil and are easy to perform. Previous studies in patients with community-acquired pneumonia have shown that these rapid tests can help doctors choose more appropriate antibiotics earlier and may improve patient outcomes. However, their benefit has not been well studied in patients with hospital-acquired pneumonia, especially in settings where multidrug-resistant bacteria are common. In these situations, early and appropriate adjustment of antibiotic therapy is particularly important for improving outcomes and ensuring the responsible use of advanced antibiotics. This study aims to compare the use of rapid diagnostic panels with standard laboratory methods in hospitalized patients with suspected pneumonia. The main focus is to evaluate how quickly and how appropriately antibiotic treatment can be adjusted after sample collection, using a structured scoring system, the Desirability of Outcome Ranking for the Management of Antimicrobial Therapy(DOOR-MAT), as well as to assess clinical outcomes. The results of this study may help determine whether rapid diagnostic testing improves patient care in real-world hospital settings. The findings could support decision-making within the Brazilian Unified Health System (SUS) regarding the adoption of this technology, and may also contribute to future analyses of its cost-effectiveness.

Interventions

• Diagnostic test Multiplex PCR-based pneumonia panel (BIOFIRE® FILMARRAY® Pneumonia Panel)
  The BIOFIRE® FILMARRAY® Pneumonia Panel is a rapid, automated molecular diagnostic test designed to detect a broad range of respiratory pathogens directly from lower respiratory tract samples, such as sputum, tracheal aspirates, or bronchoalveolar lavage. The system integrates sample preparation, nucleic acid extraction, amplification, and detection into a single, fully automated platform. The test can identify multiple bacterial and viral pathogens, as well as key antimicrobial resistance gene

Primary outcome measures

• Adequacy of antimicrobial prescriptions using the Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR-MAT). [Time frame: 24 hours after the sample receipt in the microbiology laboratory]

Secondary outcome measures (8)

• Proportion of days in under-treatment and/or overtreatment [Time frame: 7 days]
• Simulated ideal Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR-MAT) scores [Time frame: 24 hours]
• Agreement between real Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR-MAT) scores and ideal scores [Time frame: 24 hours]
• 30-day mortality [Time frame: 30 days]
• Clinical outcomes from Desirability of Outcome Ranking (DOOR) [Time frame: 2, 7 and 14 days]
• Agreement between Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR-MAT) and Clinical DOOR scores [Time frame: 14 days]
• Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR-MAT) scores in subgroups [Time frame: 24 hours]
• Cost-effectiveness analysis [Time frame: through study completion, an average of 1 year]

Eligibility criteria

Inclusion criteria

• Age ≥18 years.
• Clinical diagnosis of hospital-acquired pneumonia or clinically relevant tracheobronchitis requiring antimicrobial treatment, with or without mechanical ventilation.
• No respiratory cultures collected in the last 72 hours (except for the culture that will potentially be evaluated in the study-trigger for inclusion).
• Agreement from the patient or legal representative to sign the Informed Consent Form (ICF).

Exclusion criteria

• Inadequate respiratory samples according to laboratory cutoffs for squamous epithelial cells and polymorphonuclear leukocytes (sputum or endotracheal aspirate).
• Incarcerated populations.
• Pregnant women.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Diagnostic

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Evans SR, Rubin D, Follmann D, Pennello G, Huskins WC, Powers JH, Schoenfeld D, Chuang-Stein C, Cosgrove SE, Fowler VG Jr, Lautenbach E, Chambers HF. Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR). Clin Infect Dis. 2015 Sep 1;61(5):800-6. doi: 10.1093/cid/civ495. Epub 2015 Jun 25. PMID 26113652
• Wilson BM, Jiang Y, Jump RLP, Viau RA, Perez F, Bonomo RA, Evans SR. Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR MAT): A Framework for Assessing Antibiotic Selection Strategies in the Presence of Drug Resistance. Clin Infect Dis. 2021 Jul 15;73(2):344-350. doi: 10.1093/cid/ciaa1769. PMID 33245333
• Howard-Anderson J, Hamasaki T, Dai W, Collyar D, Rubin D, Nambiar S, Kinamon T, Leister-Tebbe H, Hill C, Geres H, Holland TL, Doernberg SB, Chambers HF, Fowler VG Jr, Evans SR, Boucher HW; Antibacterial Resistance Leadership Group. Moving Beyond Mortality: Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Hospital-Acquired Bacterial Pneumonia and Ventilator-Assoc PMID 37740559

Identifiers

NCT: NCT07585604 · 2024-0408

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗