NCT05909683

Assessing the Procalcitonin-guidance and Molecular-guided Diagnosis for Therapy of Severe Infections (the MODIFY Trial)

A Randomized Prospective Clinical Trial to Assess Procalcitonin-guidance and Molecular-guided Diagnosis as Mainstay for Therapy of Severe Infections (the MODIFY Trial)

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 190 (estimated)
• Sponsor: Hellenic Institute for the Study of Sepsis · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

MODIFY is a randomized, open-labeled, and prospective study that will be conducted in multiple Intensive Care Units (ICUs) and departments of Internal Medicine across Greece. It aims to change the traditional approach for the management of severe infections by integrating the results of BCID2, Reveal Rapid AST, and PCT, to improve patients' outcomes. Early and precise identification of the underlying causative pathogen along with the fast acquisition of the antimicrobial sensitivity results may positively impact the uncontrolled antimicrobial prescription.

Detailed description

Early administration of antimicrobials remains the mainstay of treatment of severe infections. The time until start of antimicrobials is so crucial that every hour of delay impacts considerably on mortality. In everyday clinical practice even when antimicrobials are administered early, it is impossible to know whether they are appropriate or not because cultures of specimens collected from the patient require at least 48 to 72 hours to provide some information about the type of pathogen and the antimicrobial susceptibilities. BioFire ® FilmArray ® possesses four Food and Drug Administration (FDA)-cleared panels of molecular diagnosis, capable of detecting multiple targets in less than an hour of sample handling. Among them, Blood Culture Identification 2 Panel (BCID2) covers 43 targets. BCID2 provides information on the genes of resistance to antibiotics the microorganisms carry. BCID2 combined with fast AST can, however, introduce revolutionary changes in minimizing the time until the appropriate antimicrobial is prescribed. The concept of Reveal is to provide AST for a full panel of antibiotics if one Gram-negative isolate is identified in the blood flask. Evaluation of the appropriateness of the administered therapy and decision about discontinuation or de-escalation of antimicrobials, is based on the use of biomarkers and mainly procalcitonin (PCT).

Conditions

• Sepsis

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Change of antimicrobials based on BCID2 and Reveal Rapid AST tests. Stop of antimicrobials based on PCT results.	After the patient's blood flask is flagged positive for bloodstream infection, the blood sample will be assessed in the BCID2 diagnostic test in order to identify the underlying pathogens the patient is infected with. After the identification, and in the presence of gram-negative bacteria, the sample will be assessed in the Reveal Rapid AST test to provide information about which antimicrobials the specific pathogens are sensitive to. When both the identification of the pathogen and the sensitivities are available, the central laboratory will inform the attending physicians, who are obliged to change the standard of care antimicrobial therapy administered based on the rule in Box1 of the protocol. Finally, based on the results of the procalcitonin (PCT) on the first day by day 5 when PCT value is less than 80% of the initial value or it remains below 0.5 ng/ml, the attending physicians should discontinue the antimicrobial therapy.
OTHER	Standard of Care	Standard of care practices of the specific study site. Antimicrobials will be administered based on the attending physicians' critical opinion, and discontinuation will be done based on the standard procedures of the study site.

Timeline

• Start date: 2023-09-19
• Primary completion: 2026-04-15
• Completion: 2026-04-15
• First posted: 2023-06-18
• Last updated: 2026-01-16

Locations

15 sites across 1 country: Greece