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.
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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
190
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.
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.
Intensive Care Unit of Center for Respiratory Failure, Sotiria Chest Diseases Athens General Hospital
Athens, Attica, Greece
New Multivalent Intensive Care Unit, Sotiria Chest Diseases Athens General Hospital
Athens, Attica, Greece
2nd Propaedeutic Department of Internal Medicine, Attikon University Hospital
Athens, Chaidari, Greece
4th Department of Internal Medicine, Attikon University Hospital
Athens, Chaidari, Greece
1st Department of Internal Medicine, General Hospital of Elefsina "Thriasio"
Athens, Elefsina, Greece
2nd Department of Internal Medicine, University General Hospital of Alexandroupolis
Alexandroupoli, Greece
1st Department of Internal Medicine, General Hospital of Athens KORGIALENIO-BENAKIO E.E.S.
Athens, Greece
1st Department of Internal Medicine- General Hospital of Athens GENNIMATAS
Athens, Greece
3rd University Department of Internal Medicine, Sotiria Athens General Hospital
Athens, Greece
1st Department of Internal Medicine - General Hospital of Athens Sismanoglio- Amalia Fleming
Athens, Greece
...and 5 more locations
The number of days under treatment with broad-spectrum antibiotics in the group receiving the MODIFY strategy compared to patients treated by standard of care.
The number of days under treatment with broad-spectrum antibiotics in the group receiving the MODIFY strategy compared to patients treated by standard of care.
Time frame: Through study completion, an average of 2 years
Time to first change of antimicrobial modification
Time to first change of antimicrobial modification
Time frame: Through study completion, an average of 2 years
Time to the first sterile blood culture
Time to the first sterile blood culture
Time frame: Through study completion, an average of 2 years
The number of patients in whom no changes in administered antibiotics will apply.
The number of patients in whom no changes in administered antibiotics will apply.
Time frame: Through study completion, an average of 2 years
At least 2-point decrease of baseline SOFA (Sequential organ failure assessment) score by day 7
At least 2-point decrease of baseline SOFA (Sequential organ failure assessment) score by day 7. SOFA ranges between 0-24 and the higher the score, the worst the outocome of the patient.
Time frame: Through study completion, an average of 2 years
28-day mortality
28-day mortality
Time frame: Through study completion, an average of 2 years
90-day mortality
90-day mortality
Time frame: Through study completion, an average of 2 years
Incidence of laboratory documented Clostrioides difficile infection
Incidence of laboratory documented Clostrioides difficile infection
Time frame: Through study completion, an average of 2 years
Length of hospital stay
Length of hospital stay
Time frame: Through study completion, an average of 2 years
Cost of hospitalization
Cost of hospitalization
Time frame: Through study completion, an average of 2 years
Time to escalation of antibiotics
Time to escalation of antibiotics
Time frame: Through study completion, an average of 2 years
Time to de-escalation of antibiotics
Time to de-escalation of antibiotics
Time frame: Through study completion, an average of 2 years
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