Assessing the Procalcitonin-guidance and Molecular-guided Diagnosis for Therapy of Severe Infections (the MODIFY Trial) (MODIFY)
Sepsis
About this trial
This is an interventional diagnostic trial for Sepsis focused on measuring Severe infections, Antibiotics, Procalcitonin, Blood Culture Identification 2 Panel (BCID2), Reveal Rapid AST system
Eligibility Criteria
Inclusion Criteria: Male or female For women of child-bearing potential, willingness to avoid pregnancy during the study and agreement to notify investigator if pregnancy occurs. Age more than or equal to 18 years Patients who have completed their participation in another study for more than 30 days can be included in this study. Written informed consent provided by the patient or by their legal representative in case of patients unable to consent due to sepsis onset affecting their mental capacity. Sepsis defined by the Sepsis-3 definition; this is defined separately for community-acquired sepsis and for hospital-acquired sepsis. Community-acquired sepsis is defined as any SOFA score 2 points or more for patients admitted in hospital emergencies with community-acquired pneumonia (CAP), community-acquired acute pyelonephritis (AP) or community-acquired primary bacteremia (BSI). CAP, AP and BSI are considered community-acquired for patients who have no history of hospitalization lasting more than 2 days the last 90 days or who are not under hemodialysis or who are not residents of long-term care facilities. Hospital-acquired sepsis is defined as any SOFA score increase by 2 points or more from the admission SOFA score for patients with onset of hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), acute pyelonephritis (AP) or primary bacteremia (BSI) at least 48 hours after hospital admission. For patients with history of hospitalization lasting more than 2 days the last 90 days or who are under hemodialysis or who are residents of long-term care facilities and are admitted to hospital with HAP, VAP, AP and BSI the definition of hospital-acquired sepsis applies. In this case, the baseline SOFA score is considered as the known SOFA score before infection onset. Presence of one of the following infections: community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), acute pyelonephritis (AP) and primary bacteremia (BSI). Positive blood culture Exclusion Criteria: Failure to obtain written consent to participate Previous enrollment in this study within the past 90 days. Patients enrolled in another study will not be accepted. Patients in pregnancy or breastfeeding. Women of child-bearing potential will be screened by a urine pregnancy test before inclusion in the study Patients receiving prolonged antibiotic therapies (e.g. endocarditis, implantable device-associated infection, cerebral/hepatic abscess, osteomyelitis, meningitis) Patients with severe infections due to viruses or parasites (e.g. Dengue, Toxoplasma gondii, Plasmodium spp.) Patients with infection due to Mycobacterium tuberculosis. Patients suffering from cystic fibrosis Severely immunocompromised patients such as a) patients with infection by the human immunodeficiency virus and with a CD4 count of less than 200 cells/mm3; b) neutropenic patients with less than 500 neutrophils/mm3; and c) patients with solid organ transplantation.
Sites / Locations
- 2nd Propaedeutic Department of Internal Medicine, Attikon University HospitalRecruiting
- 4th Department of Internal Medicine, Attikon University HospitalRecruiting
- 1st Department of Internal Medicine, General Hospital of Elefsina "Thriasio"
- 2nd Department of Internal Medicine, University General Hospital of Alexandroupolis
- 1st Department of Internal Medicine, General Hospital of Athens KORGIALENIO-BENAKIO E.E.S.
- 3rd University Department of Internal Medicine, Sotiria Athens General HospitalRecruiting
- 2nd Department of Internal Medicine, General Hospital of Piraeus "Tzaneio"
- 1st University Department of Internal Medicine, AHEPA University General Hospital of Thessaloniki
- Intensive Care Unit, Ippokrateion General Hospital
Arms of the Study
Arm 1
Arm 2
Sham Comparator
Experimental
Standard-of-care
MODIFY strategy
These patients will receive antibiotics according to standard practice of the attending physicians. The central lab will feedback to attending physicians and investigators the results of the conventional blood cultures and AST according to the routine SOP. The attending physicians and investigators will be allowed to decide for any change of antimicrobial treatment based on the results of conventional blood cultures provided to them by the central lab or any other culture provided to them by their hospital. Antibiotics will be stopped according to the local standard practice. BCID2, Reveal Rapid AST and PCT will be performed in the samples of these patients, attending physicians will not be provided such information.
These patients will start antibiotics according to standard practice of the attending physicians. It is anticipated that attending physicians will be informed in maximum 5 hours after randomization about the results of BCID2 including carriage of resistance genes and of the Reveal Rapid AST in the case of Gram-negative isolates. Physicians and investigators receiving this information are obliged to change the empirically prescribed antibiotics according to the rule provided in Box 1. The attending physicians and investigators will be allowed to decide for any change of antimicrobial treatment based on the results of conventional blood cultures provided to them by the central lab or any other culture provided to them by their hospital. PCT will be measured on day 1 and then daily starting from day 5. Attending physicians will be advised to discontinue antimicrobials 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.