SepsisPROGRESSNCT03333304
A Clinical Trial of Procalcitonin-guided Antimicrobial Therapy in Sepsis
A study testing Procalcitonin measurement in people with Sepsis, run by Hellenic Institute for the Study of Sepsis at 7 sites in Greece.
Trial summary
The aim of the study is to demonstrate if using one procalcitonin (PCT)-guided rule of stop of antimicrobials, the incidence of infections by C.difficile and by Multi-Drug-Resistant (MDR) bacteria during the next six months may be significantly decreased. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis
- What is being tested?
- Procalcitonin measurement
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 266 participants
- Where
- 7 sitesGreece
- Study dates
- 24 Oct 2017to 20 Jul 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- In case of women, unwillingness to remain pregnant during the study period.
- Age more than or equal to 18 years
- Sequential Organ Failure Assessment (SOFA) score more than or equal to 2 points for patients admitted in the emergencies and with a more than or equal to a 2-point increase of admission SOFA score for hospitalized patients.
- Presence of one of the following infections: community-acquired pneumonia, hospital-acquired pneumonia, ventilator-associated pneumonia, bacteremia and acute pyelonephritis. Any infection with onset more than 48 hours post hospital admission is considered one hospital-acquired infection.
Who cannot join
- Failure to obtain written consent to participate
- 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 infected with Mycobacterium tuberculosis.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Greece7 sites
1st Department of Internal Medicine, General Hospital of Athens "G. Gennimatas"
Athens, 11527
3rd Department of Internal Medicine, Sotiria Athens General Hospital
Athens, 11527
4th Department of Internal Medicine, Attikon University Hospital
Athens, 12462
2nd Department of internal Medicine, General Hospital of Attiki "Sismanogleio"
Athens, 15126
1st Department of Internal Medicine, General Hospital of Elefsina "Thriasio"
Athens, 19600
2nd Department of Internal Medicine, General Hospital of Elefsina "Thriasio"
Athens, 19600
2nd Department of Internal Medicine, General Hospital of Piraeus "Tzaneio"
Piraeus, 18536
About this study
Official title: A Randomized Prospective Clinical Trial to Assess the Role of Procalcitonin-guided Antimicrobial Therapy to Reduce Long-term Infections Sequelae
The aim of the study is to demonstrate if using one procalcitonin (PCT)-guided rule of stop of antimicrobials, the incidence of infections by C.difficile and by Multi-Drug-Resistant (MDR) bacteria during the next six months may be significantly decreased.
Read the detailed description
Early administration of antimicrobials remains the mainstay of treatment of severe infections. Current guidelines of management of severe sepsis suggest that initial therapy of a patient should be reviewed after 48 to 72 hours. At that stage some patients are doing well, whereas others fail to respond. When microbiology cultures of biological specimens fail to provide information for the microbial cause of an infection and susceptibilities to antimicrobials, antimicrobial stewardship relies on the use of biomarkers and mainly procalcitonin (PCT). Data so far, suggest that early changes of serum PCT can inform about the prognosis of the septic patient, with greater values reflecting a worse outcome and higher mortality and that serial measurements within 48-72 hours provide adequate information of the appropriateness of the administered antimicrobials. Moreover the use of a procalcitonin guided-treatment in surgical as well as in non-surgical critically-ill patients, is seen to be non-inferior to the standard antibiotic approach and leads to a shorter antibiotic exposure, having possible beneficial effect on reducing microbial resistance and therapy costs.
In the largest study conducted so far, de Jong et al showed that PCT-guided stop of treatment was not only safe compared with standard of care antibiotic duration, but also led to a better outcome i.e. significant decrease of both 28-day and 1-year mortality. The results of this study are a major contribution in the field of critical care since they prove for the first time that PCT guidance of antimicrobial treatment allows not only proper antimicrobial stewardship but it is also associated with survival benefit. However, de Jong et al did not provide findings to explain the underlying mechanism of survival benefit. As a rule critically ill patients run two major risks coming from the long-term administration of antimicrobials; the first is infections by Clostridium difficile coming from the ecological damage of gut flora and the second is the risk of infections by multidrug-resistant (MDR) bacteria colonizing the gut. MDR is emerging after the ecological pressure of broad-spectrum antimicrobial usually administered to the critically ill patient.
- Conditions
- Sepsis
- Being tested
- Procalcitonin measurement
- Keywords
- Procalcitonin
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Procalcitonin measurementDiagnostic test
Discontinuation of antimicrobials according to Procalcitonin Kinetics
| Study group | Role | What they receive |
|---|---|---|
| PCT group | Experimental | Procalcitonin measurement and Discontinuation of antimicrobials according to Procalcitonin kinetics Receives: Diagnostic Test: Procalcitonin measurement |
| Standard of care | No intervention | Standard practice |
What is being measured
The primary outcome is the main question the study is designed to answer.
The change of infection-associated adverse events rate. The infection-associated adverse events rate are any case of Clostridium Difficile Infection (CDI) or infection by MDR or infection-related death.
The change of infection-associated adverse events rate. The infection-associated adverse events rate are any case of Clostridium Difficile Infection (CDI) or infection by MDR or infection-related death.
Measured: 6 months
Secondary outcomes (11)
Infection-associated adverse events rate
Time to first infection-associated adverse events rate
Measured: 6 months
Clostridium difficile Infection
Rate of infections by Clostridium difficile
Measured: 6 months
Infections by MDR
Rate of infections by MDR
Measured: 6 months
Mortality
Mortality
Measured: 28 days
Mortality
Mortality
Measured: 6 months
Stool colonization by C.difficile
Rate stool positive for GDH by C.difficile
Measured: 6 months
Stool colonization by MDR
Rate of stool colonization by MDR
Measured: 6 months
Microbiome composition
Microbiome composition
Measured: 28 days
Changes of the microbiome
Changes of the microbiome
Measured: 28 days
Consumption of antimicrobials during hospitalization
Consumption of antimicrobials during hospitalization
Measured: 28 days
Cost of hospitalization
Real cost of hospitalization i.e medicines administered and interventions performed, in Euro, between the two groups of treatment.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start24 Oct 2017
- Primary completion20 Jan 2019
- Study completion20 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be randomized at 1:1 ratio by a separate list per study site into two treatment groups. The two groups of treatment will be as follows: * Standard of care: these patients will receive antimicrobials according to standard practice of the attending physicians but PCT will not be measured and antimicrobials will be stopped according to the local standard practice. * PCT group: these patients will receive antimicrobials according to standard practice of the attending physicians and antimicrobials will be discontinued according to PCT kinetics.
- Masking
- None (open label)
- Enrolment
- 266 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hellenic Institute for the Study of Sepsis
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anastasia Antoniadou, MD, PhD, Principal investigator, National Kapodistrian University of Athens, Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03333304
- Sponsor's protocol ID
- PROGRESS
- Acronym
- PROGRESS
- Status last verified
- Dec 2019
- First submitted
- 23 Oct 2017
- Last updated
- 17 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Kyriazopoulou E, Stylianakis E, Damoraki G, Spyrou A, Symbardi S, Chrysos G, Adamis G, Giamarellos-Bourboulis EJ. Development of antibiotic-associated diarrhea in sepsis patients is associated with dysbiosis at baseline: Data from the PROGRESS Controlled Trial. Int J Antimicrob Agents. 2026 Aug 20:107979. doi: 10.1016/j.ijantimicag.2026.107979. Online ahead of print.
PubMed 42624437Kyriazopoulou E, Stylianakis E, Damoraki G, Koufargyris P, Kollias I, Katrini K, Drakou E, Marousis K, Spyrou A, Symbardi S, Alexiou N, Alexiou Z, Lada M, Poulakou G, Chrysos G, Adamis G, Giamarellos-Bourboulis EJ. Procalcitonin-guided early cessation of antibiotics prevents gut inflammation and preserves gut microbiome: Data from the PROGRESS controlled trial. Int J Antimicrob Agents. 2025 Aug;66(2):107507. doi: 10.1016/j.ijantimicag.2025.107507. Epub 2025 Apr 9.
PubMed 40216091Kyriazopoulou E, Karageorgos A, Liaskou-Antoniou L, Koufargyris P, Safarika A, Damoraki G, Lekakis V, Saridaki M, Adamis G, Giamarellos-Bourboulis EJ. BioFire(R) FilmArray(R) Pneumonia Panel for Severe Lower Respiratory Tract Infections: Subgroup Analysis of a Randomized Clinical Trial. Infect Dis Ther. 2021 Sep;10(3):1437-1449. doi: 10.1007/s40121-021-00459-x. Epub 2021 Jun 13.
PubMed 34120316Kyriazopoulou E, Liaskou-Antoniou L, Adamis G, Panagaki A, Melachroinopoulos N, Drakou E, Marousis K, Chrysos G, Spyrou A, Alexiou N, Symbardi S, Alexiou Z, Lagou S, Kolonia V, Gkavogianni T, Kyprianou M, Anagnostopoulos I, Poulakou G, Lada M, Makina A, Roulia E, Koupetori M, Apostolopoulos V, Petrou D, Nitsotolis T, Antoniadou A, Giamarellos-Bourboulis EJ. Procalcitonin to Reduce Long-Term Infection-associated Adverse Events in Sepsis. A Randomized Trial. Am J Respir Crit Care Med. 2021 Jan 15;203(2):202-210. doi: 10.1164/rccm.202004-1201OC.
PubMed 32757963
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Prospective Clinical Trial to Assess the Role of Procalcitonin-guided Antimicrobial Therapy to Reduce Long-term Infections Sequelae
- ClinicalTrials.gov ID
- NCT03333304
- Acronym / sponsor ID
- PROGRESS / PROGRESS
- Conditions
- Sepsis
- Keywords
- Procalcitonin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 266 participants (actual)
- Lead sponsor
- Hellenic Institute for the Study of SepsisUniversity, hospital or other
- Study start
- 24 Oct 2017 (actual)
- Primary completion
- 20 Jan 2019 (actual)
- Study completion
- 20 Jul 2019 (actual)
- First posted
- 6 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to demonstrate if using one procalcitonin (PCT)-guided rule of stop of antimicrobials, the incidence of infections by C.difficile and by Multi-Drug-Resistant (MDR) bacteria during the next six months may be significantly decreased.
Detailed description
Early administration of antimicrobials remains the mainstay of treatment of severe infections. Current guidelines of management of severe sepsis suggest that initial therapy of a patient should be reviewed after 48 to 72 hours. At that stage some patients are doing well, whereas others fail to respond. When microbiology cultures of biological specimens fail to provide information for the microbial cause of an infection and susceptibilities to antimicrobials, antimicrobial stewardship relies on the use of biomarkers and mainly procalcitonin (PCT). Data so far, suggest that early changes of serum PCT can inform about the prognosis of the septic patient, with greater values reflecting a worse outcome and higher mortality and that serial measurements within 48-72 hours provide adequate information of the appropriateness of the administered antimicrobials. Moreover the use of a procalcitonin guided-treatment in surgical as well as in non-surgical critically-ill patients, is seen to be non-inferior to the standard antibiotic approach and leads to a shorter antibiotic exposure, having possible beneficial effect on reducing microbial resistance and therapy costs.
In the largest study conducted so far, de Jong et al showed that PCT-guided stop of treatment was not only safe compared with standard of care antibiotic duration, but also led to a better outcome i.e. significant decrease of both 28-day and 1-year mortality. The results of this study are a major contribution in the field of critical care since they prove for the first time that PCT guidance of antimicrobial treatment allows not only proper antimicrobial stewardship but it is also associated with survival benefit. However, de Jong et al did not provide findings to explain the underlying mechanism of survival benefit. As a rule critically ill patients run two major risks coming from the long-term administration of antimicrobials; the first is infections by Clostridium difficile coming from the ecological damage of gut flora and the second is the risk of infections by multidrug-resistant (MDR) bacteria colonizing the gut. MDR is emerging after the ecological pressure of broad-spectrum antimicrobial usually administered to the critically ill patient.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients will be randomized at 1:1 ratio by a separate list per study site into two treatment groups. The two groups of treatment will be as follows: * Standard of care: these patients will receive antimicrobials according to standard practice of the attending physicians but PCT will not be measured and antimicrobials will be stopped according to the local standard practice. * PCT group: these patients will receive antimicrobials according to standard practice of the attending physicians and antimicrobials will be discontinued according to PCT kinetics.
| Arm | Type | Receives |
|---|---|---|
| PCT group | Experimental | Diagnostic Test: Procalcitonin measurementProcalcitonin measurement and Discontinuation of antimicrobials according to Procalcitonin kinetics |
| Standard of care | No intervention | –Standard practice |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female
- In case of women, unwillingness to remain pregnant during the study period.
- Age more than or equal to 18 years
- Sequential Organ Failure Assessment (SOFA) score more than or equal to 2 points for patients admitted in the emergencies and with a more than or equal to a 2-point increase of admission SOFA score for hospitalized patients.
- Presence of one of the following infections: community-acquired pneumonia, hospital-acquired pneumonia, ventilator-associated pneumonia, bacteremia and acute pyelonephritis. Any infection with onset more than 48 hours post hospital admission is considered one hospital-acquired infection.
Key exclusion criteria (5 listed)
- Failure to obtain written consent to participate
- 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 infected with Mycobacterium tuberculosis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Procalcitonin measurementDiscontinuation of antimicrobials according to Procalcitonin Kinetics | Diagnostic test | PCT group |
Primary outcome
The change of infection-associated adverse events rate. The infection-associated adverse events rate are any case of Clostridium Difficile Infection (CDI) or infection by MDR or infection-related death.
Time frame: 6 months
The change of infection-associated adverse events rate. The infection-associated adverse events rate are any case of Clostridium Difficile Infection (CDI) or infection by MDR or infection-related death.
11 secondary outcomes
Infection-associated adverse events rate
Time frame: 6 months
Clostridium difficile Infection
Time frame: 6 months
Infections by MDR
Time frame: 6 months
Mortality
Time frame: 28 days
Mortality
Time frame: 6 months
Stool colonization by C.difficile
Time frame: 6 months
Stool colonization by MDR
Time frame: 6 months
Microbiome composition
Time frame: 28 days
Changes of the microbiome
Time frame: 28 days
Consumption of antimicrobials during hospitalization
Time frame: 28 days
Cost of hospitalization
Time frame: 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Derived from this study: PubMed 42624437Kyriazopoulou E, Stylianakis E, Damoraki G, Spyrou A, Symbardi S, Chrysos G, Adamis G, Giamarellos-Bourboulis EJ. Development of antibiotic-associated diarrhea in sepsis patients is associated with dysbiosis at baseline: Data from the PROGRESS Controlled Trial. Int J Antimicrob Agents. 2026 Aug 20:107979. doi: 10.1016/j.ijantimicag.2026.107979. Online ahead of print.
- Derived from this study: PubMed 40216091Kyriazopoulou E, Stylianakis E, Damoraki G, Koufargyris P, Kollias I, Katrini K, Drakou E, Marousis K, Spyrou A, Symbardi S, Alexiou N, Alexiou Z, Lada M, Poulakou G, Chrysos G, Adamis G, Giamarellos-Bourboulis EJ. Procalcitonin-guided early cessation of antibiotics prevents gut inflammation and preserves gut microbiome: Data from the PROGRESS controlled trial. Int J Antimicrob Agents. 2025 Aug;66(2):107507. doi: 10.1016/j.ijantimicag.2025.107507. Epub 2025 Apr 9.
- Derived from this study: PubMed 34120316Kyriazopoulou E, Karageorgos A, Liaskou-Antoniou L, Koufargyris P, Safarika A, Damoraki G, Lekakis V, Saridaki M, Adamis G, Giamarellos-Bourboulis EJ. BioFire(R) FilmArray(R) Pneumonia Panel for Severe Lower Respiratory Tract Infections: Subgroup Analysis of a Randomized Clinical Trial. Infect Dis Ther. 2021 Sep;10(3):1437-1449. doi: 10.1007/s40121-021-00459-x. Epub 2021 Jun 13.
- Derived from this study: PubMed 32757963Kyriazopoulou E, Liaskou-Antoniou L, Adamis G, Panagaki A, Melachroinopoulos N, Drakou E, Marousis K, Chrysos G, Spyrou A, Alexiou N, Symbardi S, Alexiou Z, Lagou S, Kolonia V, Gkavogianni T, Kyprianou M, Anagnostopoulos I, Poulakou G, Lada M, Makina A, Roulia E, Koupetori M, Apostolopoulos V, Petrou D, Nitsotolis T, Antoniadou A, Giamarellos-Bourboulis EJ. Procalcitonin to Reduce Long-Term Infection-associated Adverse Events in Sepsis. A Randomized Trial. Am J Respir Crit Care Med. 2021 Jan 15;203(2):202-210. doi: 10.1164/rccm.202004-1201OC.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anastasia Antoniadou, MD, PhD principal investigator
National Kapodistrian University of Athens, Medical School
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Procalcitonin measurement in people with Sepsis, run by Hellenic Institute for the Study of Sepsis at 7 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 5 inclusion and 5 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: finished, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 change of infection-associated adverse events rate. The infection-associated adverse events rate are any case of Clostridium Difficile Infection (CDI) or infection by MDR or infection-related death. (time frame: 6 months). 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 NCT03333304, which also lists 4 linked publications.
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 17 Dec 2019.