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SepsisPhase 3MODIFYNCT05909683

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

A Phase 3 study testing Change of antimicrobials based on BCID2 and Reveal Rapid AST tests. Stop of antimicrobials based on PCT results. in people with Sepsis, run by Hellenic Institute for the Study of Sepsis at 15 sites in Greece.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Sepsis
What is being tested?
Change of antimicrobials based on BCID2 and Reveal Rapid AST tests. Stop of antimicrobials based on PCT results.
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
190 participants
Where
15 sitesGreece
Study dates
19 Sep 2023to 15 Apr 2026
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

Greece15 sites

  • 2nd Department of Internal Medicine, University General Hospital of Alexandroupolis

    Alexandroupoli

  • Intensive Care Unit of Center for Respiratory Failure, Sotiria Chest Diseases Athens General Hospital

    Athens, Attica, 11527

  • New Multivalent Intensive Care Unit, Sotiria Chest Diseases Athens General Hospital

    Athens, Attica, 11527

  • 2nd Propaedeutic Department of Internal Medicine, Attikon University Hospital

    Athens, Chaidari, 12462

  • 4th Department of Internal Medicine, Attikon University Hospital

    Athens, Chaidari, 12462

  • 1st Department of Internal Medicine, General Hospital of Elefsina "Thriasio"

    Athens, Elefsina, 19600

  • 1st Department of Internal Medicine, General Hospital of Athens KORGIALENIO-BENAKIO E.E.S.

    Athens, 11526

  • 1st Department of Internal Medicine- General Hospital of Athens GENNIMATAS

    Athens, 11527

  • 3rd University Department of Internal Medicine, Sotiria Athens General Hospital

    Athens, 11527

  • 1st Department of Internal Medicine - General Hospital of Athens Sismanoglio- Amalia Fleming

    Athens, 15126

  • 3rd Department of Internal Medicine - General State Hospital of Nikaia "Saint Panteleimon" - West Attica General Hospital "Agia Varvara"

    Athens, 18454

  • Clinic of Intensive Care and Pulmonary Diseases, Aghioi Anargyroi Kifissia General Oncologic Hospital

    Kifissia, 14564

  • 2nd Department of Internal Medicine, General Hospital of Piraeus "Tzaneio"

    Piraeus, 18536

  • 1st University Department of Internal Medicine, AHEPA University General Hospital of Thessaloniki

    Thessaloniki, 54636

  • Intensive Care Unit, Ippokrateion General Hospital

    Thessaloniki, 54642

Other trials in Greece

About this study

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

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.

Read the 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
Being tested
Change of antimicrobials based on BCID2 and Reveal Rapid AST tests. Stop of antimicrobials based on PCT results., Standard of Care
Keywords
Severe infections, Antibiotics, Procalcitonin, Blood Culture Identification 2 Panel (BCID2), Reveal Rapid AST system
Medical subject headings
Sepsis, Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Change of antimicrobials based on BCID2 and Reveal Rapid AST tests. Stop of antimicrobials based on PCT results.Diagnostic test

    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 CareOther

    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.

Study groups in NCT05909683
Study groupRoleWhat they receive
Standard-of-careSham comparatorThese 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.
Receives: Other: Standard of Care
MODIFY strategyExperimentalThese 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.
Receives: Diagnostic Test: Change of antimicrobials based on BCID2 and Reveal Rapid AST tests. Stop of antimicrobials based on PCT results.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Through study completion, an average of 2 years

Secondary outcomes (11)

  1. Time to first change of antimicrobial modification

    Time to first change of antimicrobial modification

    Measured: Through study completion, an average of 2 years

  2. Time to the first sterile blood culture

    Time to the first sterile blood culture

    Measured: Through study completion, an average of 2 years

  3. 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.

    Measured: Through study completion, an average of 2 years

  4. 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.

    Measured: Through study completion, an average of 2 years

  5. 28-day mortality

    28-day mortality

    Measured: Through study completion, an average of 2 years

  6. 90-day mortality

    90-day mortality

    Measured: Through study completion, an average of 2 years

  7. Incidence of laboratory documented Clostrioides difficile infection

    Incidence of laboratory documented Clostrioides difficile infection

    Measured: Through study completion, an average of 2 years

  8. Length of hospital stay

    Length of hospital stay

    Measured: Through study completion, an average of 2 years

  9. Cost of hospitalization

    Cost of hospitalization

    Measured: Through study completion, an average of 2 years

  10. Time to escalation of antibiotics

    Time to escalation of antibiotics

    Measured: Through study completion, an average of 2 years

  11. Time to de-escalation of antibiotics

    Time to de-escalation of antibiotics

    Measured: Through study completion, an average of 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jun 2023
  2. Study start19 Sep 2023
  3. Primary completion15 Apr 2026 (estimated)
  4. Study completion15 Apr 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Diagnosis
Allocation
Randomised
Intervention model
Parallel groups
Model description
According to protocol study intervention is not study drug administration; intervention includes two steps: modification of antibiotics administered; duration of antibiotic treatment. SOC patients will receive antibiotics according to standard practice of the attending physicians. MODIFY strategy group patients will start antibiotics according to standard practice. They will be informed after randomization about the results of BCID2, Reveal Rapid AST and PCT. Physicians and investigators receiving this information are obliged to change the empirically prescribed antibiotics (escalate, de- escalate or stop) aiming to improve patient outcomes. Exceptions to overrule this algorithm will be accepted for medically unstable patients.
Masking
None (open label)
Enrolment
190 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05909683
Sponsor's protocol ID
MODIFY
Other IDs
2022-502962-26-00
Acronym
MODIFY
Status last verified
Jan 2026
First submitted
9 Jun 2023
Last updated
16 Jan 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Change of antimicrobials based on BCID2 and Reveal Rapid AST tests. Stop of antimicrobials based on PCT results. in people with Sepsis, run by Hellenic Institute for the Study of Sepsis at 15 sites in Greece.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 16 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05909683.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jan 2026.

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