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A Clinical Trial of Procalcitonin-guided Antimicrobial Therapy in Sepsis (PROGRESS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03333304
Recruitment Status : Active, not recruiting
First Posted : November 6, 2017
Last Update Posted : February 21, 2019
Sponsor:
Information provided by (Responsible Party):
Hellenic Institute for the Study of Sepsis

Brief 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.

Condition or disease Intervention/treatment Phase
Sepsis Diagnostic Test: Procalcitonin measurement Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 281 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
Official Title: A Randomized Prospective Clinical Trial to Assess the Role of Procalcitonin-guided Antimicrobial Therapy to Reduce Long-term Infections Sequelae
Actual Study Start Date : October 24, 2017
Actual Primary Completion Date : January 20, 2019
Estimated Study Completion Date : July 20, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antibiotics Sepsis

Arm Intervention/treatment
Experimental: PCT group
Procalcitonin measurement and Discontinuation of antimicrobials according to Procalcitonin kinetics
Diagnostic Test: Procalcitonin measurement
Discontinuation of antimicrobials according to Procalcitonin Kinetics

No Intervention: Standard of care
Standard practice



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Infection-associated adverse events rate [ Time Frame: 6 months ]
    Time to first infection-associated adverse events rate

  2. Clostridium difficile Infection [ Time Frame: 6 months ]
    Rate of infections by Clostridium difficile

  3. Infections by MDR [ Time Frame: 6 months ]
    Rate of infections by MDR

  4. Mortality [ Time Frame: 28 days ]
    Mortality

  5. Mortality [ Time Frame: 6 months ]
    Mortality

  6. Stool colonization by C.difficile [ Time Frame: 6 months ]
    Rate stool positive for GDH by C.difficile

  7. Stool colonization by MDR [ Time Frame: 6 months ]
    Rate of stool colonization by MDR

  8. Microbiome composition [ Time Frame: 28 days ]
    Microbiome composition

  9. Changes of the microbiome [ Time Frame: 28 days ]
    Changes of the microbiome

  10. Consumption of antimicrobials during hospitalization [ Time Frame: 28 days ]
    Consumption of antimicrobials during hospitalization

  11. Cost of hospitalization [ Time Frame: 28 days ]
    Real cost of hospitalization i.e medicines administered and interventions performed, in Euro, between the two groups of treatment.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03333304


Locations
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Greece
1st Department of Internal Medicine, General Hospital of Athens "G. Gennimatas"
Athens, Greece, 11527
3rd Department of Internal Medicine, Sotiria Athens General Hospital
Athens, Greece, 11527
4th Department of Internal Medicine, Attikon University Hospital
Athens, Greece, 12462
2nd Department of internal Medicine, General Hospital of Attiki "Sismanogleio"
Athens, Greece, 15126
1st Department of Internal Medicine, General Hospital of Elefsina "Thriasio"
Athens, Greece, 19600
2nd Department of Internal Medicine, General Hospital of Elefsina "Thriasio"
Athens, Greece, 19600
2nd Department of Internal Medicine, General Hospital of Piraeus "Tzaneio"
Piraeus, Greece, 18536
Sponsors and Collaborators
Hellenic Institute for the Study of Sepsis
Investigators
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Principal Investigator: Anastasia Antoniadou, MD, PhD National Kapodistrian University of Athens, Medical School

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Responsible Party: Hellenic Institute for the Study of Sepsis
ClinicalTrials.gov Identifier: NCT03333304     History of Changes
Other Study ID Numbers: PROGRESS
First Posted: November 6, 2017    Key Record Dates
Last Update Posted: February 21, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hellenic Institute for the Study of Sepsis:
Procalcitonin

Additional relevant MeSH terms:
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Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Anti-Infective Agents
Anti-Bacterial Agents