A Clinical Trial of Procalcitonin-guided Antimicrobial Therapy in Sepsis

Sepsis Clinical Trial

— PROGRESS  

Official title:

A Randomized Prospective Clinical Trial to Assess the Role of Procalcitonin-guided Antimicrobial Therapy to Reduce Long-term Infections Sequelae

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03333304
• Other study ID #: PROGRESS
• Status: Completed
• Phase: N/A
• Start date: October 24, 2017
• Est. completion date: July 20, 2019

Study information

• Verified date: December 2019
• Source: Hellenic Institute for the Study of Sepsis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 266
• Est. completion date: July 20, 2019
• Est. primary completion date: January 20, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Sepsis

Intervention

Diagnostic Test:
• Procalcitonin measurement
Discontinuation of antimicrobials according to Procalcitonin Kinetics

Locations

Country	Name	City	State
Greece	1st Department of Internal Medicine, General Hospital of Athens "G. Gennimatas"	Athens
Greece	1st Department of Internal Medicine, General Hospital of Elefsina "Thriasio"	Athens
Greece	2nd Department of internal Medicine, General Hospital of Attiki "Sismanogleio"	Athens
Greece	2nd Department of Internal Medicine, General Hospital of Elefsina "Thriasio"	Athens
Greece	3rd Department of Internal Medicine, Sotiria Athens General Hospital	Athens
Greece	4th Department of Internal Medicine, Attikon University Hospital	Athens
Greece	2nd Department of Internal Medicine, General Hospital of Piraeus "Tzaneio"	Piraeus

Sponsors (1)

Lead Sponsor	Collaborator
Hellenic Institute for the Study of Sepsis

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	6 months
Secondary	Infection-associated adverse events rate	Time to first infection-associated adverse events rate	6 months
Secondary	Clostridium difficile Infection	Rate of infections by Clostridium difficile	6 months
Secondary	Infections by MDR	Rate of infections by MDR	6 months
Secondary	Mortality	Mortality	28 days
Secondary	Mortality	Mortality	6 months
Secondary	Stool colonization by C.difficile	Rate stool positive for GDH by C.difficile	6 months
Secondary	Stool colonization by MDR	Rate of stool colonization by MDR	6 months
Secondary	Microbiome composition	Microbiome composition	28 days
Secondary	Changes of the microbiome	Changes of the microbiome	28 days
Secondary	Consumption of antimicrobials during hospitalization	Consumption of antimicrobials during hospitalization	28 days
Secondary	Cost of hospitalization	Real cost of hospitalization i.e medicines administered and interventions performed, in Euro, between the two groups of treatment.	28 days