KInetics of Procalcitonin to Reduce Unnecessary aNtibiotic Use - Comparing Procalcitonin Kinetics-guided and Absolute Procalcitonin Value-guided Antibiotic Initiation in Reducing Unnecessary Antibiotic Use in Critically Ill Patients

NCT ID: NCT07211620

Last Updated: 2026-01-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-11-06

Study Completion Date

2027-12-31

Brief Summary

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The study aims to compare the efficacy and safety of an absolute procalcitonin (PCT) value-guided antibiotic initiation protocol and a protocol using the kinetics of PCT (the difference between the actual and the previous day value) in hemodynamically stable critically ill patients with suspected new-onset infection on admission or during ICU stay.

The main question it aims to answer:

* Can the investigators decrease the number of unnecessary AB therapies using the kinetics of PCT insted of using absolute PCT values?
* Is it safe to use PCT kinetics together with the clinical picture to guide AB initiation? AB therapy will be initiated according to predefined PCT protocols (Kinetics and Absolute Group). After 72 hours of treatment, an independent multidisciplinary team (infectologist, microbiologist and intensivist) will decide about the necessity of the treatment with all the relevant results in hand.

Detailed Description

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Appropriate antibiotic (AB) therapy is still a big challenge in intensive care units today. More than 50% of our patients are considered potentially infected, and infection alone can double mortality; however, infection is later confirmed in less than 60% of patients admitted with the initial diagnosis of sepsis. According to previous studies, at least every fifth patient in intensive care units receives unnecessary antibiotics (ABs), leading to the well-known adverse effects of ABs without any benefit. The emergence of AB resistance has been associated with 700,000 avoidable deaths in 2014, and WHO estimates that it will contribute to the death of 10 million people by 2050.

Procalcitonin (PCT) is one of the most studied inflammatory biomarkers. Several randomized controlled trials (RCTs) and their meta-analyses concluded that PCT-guided antibiotic treatment could reduce the length of AB therapy without adverse effects; moreover, it may be associated with reduced 28-day mortality, which was also confirmed by our study in 2023. Accordingly, the current sepsis guideline recommends the combined evaluation of the clinical picture and PCT when stopping AB therapy; however, it contains a weak recommendation against using PCT when starting the treatment. The latter proposition is based on three studies with a significant number of surgical patients (around 40%) in two of them, in whom the applied PCT cut-off (0.5-1 ng/ml) presumably was too low, supported by several previous studies. Therefore, the overuse of ABs was more or less hardcoded into the protocol.

Kinetics of an inflammatory biomarker can carry much more information about the host response to infection instead of a single value. In a prospective observational study by Trasy et al., early PCT kinetics (PCT change between the day of suspected infection and the previous 24 hours) predicted infection, while PCT did not change in the group of patients in whom the infection was later ruled out. Tsangaris and his colleagues measured PCT daily in critically ill patients. The investigators noted a two-fold increase in PCT levels between the day of fever onset and the previous day if the patients had an infection, while there was no difference in the PCT values if the participants had no infection.

Based on these findings, the investigators created a protocol to reduce the number of unnecessary antibiotic therapies using the kinetics of PCT.

Conditions

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Infection Sepsis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

DOUBLE

Participants Outcome Assessors
Nurses

Study Groups

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Kinetics

In the case of a suspected new-onset infection, the treating physician starts antibiotic therapy according to a predefined protocol depending on the kinetics of PCT.

Group Type EXPERIMENTAL

Kinetics

Intervention Type OTHER

Initiation of the AB therapy is recommended for the clinician if PCT ≥ 0.5 ng/ml and PCT elevation ≥100% from the previous day's value.

Absolute

In the case of a new-onset infection, starting ABs is recommended depending on the actual absolute value of PCT.

Group Type EXPERIMENTAL

Absolute

Intervention Type OTHER

According to the antibiotic protocol, starting ABs is recommended if PCT ≥ 0.5 ng/ml.

Interventions

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Kinetics

Initiation of the AB therapy is recommended for the clinician if PCT ≥ 0.5 ng/ml and PCT elevation ≥100% from the previous day's value.

Intervention Type OTHER

Absolute

According to the antibiotic protocol, starting ABs is recommended if PCT ≥ 0.5 ng/ml.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Adult (18 years \< ) non-surgical, surgical, or trauma patients
* Suspected new-onset infection on admission or during ICU stay
* The source of infection is known or highly suspected, and source control has been implemented if needed (i.e., removal of an infected device (e.g., central line, endoprosthesis)
* Two PCT values are available - one on the day of suspicion of infection and one 24±4 hours earlier.
* Microbiology sampling has to be performed (according to all presumed sources - blood culture -aerobic and anaerobic, lower respiratory tract sample (tracheal aspirate/bronchoalveolar lavage), urine, etc.).
* Written informed consent of the patient (or legal guardian if the patient cannot provide consent)

Exclusion Criteria

* Septic shock (hypotension requiring vasopressor therapy to maintain mean blood pressure of 65 mmHg or greater and having a serum lactate level greater than 2 mmol/L after adequate fluid resuscitation)
* Infections for which long-term antibiotic treatment is strongly recommended (e.g., infective endocarditis, osteoarticular infections, chronic prostatitis, tuberculosis)
* Infections related to primary surgical intervention and adequate source control cannot be guaranteed (e.g., fecal peritonitis, pancreatic necrosectomy, infective necrotizing fascitis - i.e., Fournier's gangrene),
* Indisputable infections (e.g., hepatic abscess, empyema)
* Poor chance of survival (i.e., expected ICU stay less than 24 hours or initial Acute Physiology and Health Evaluation Score II (APACHE II) \>30)
* Admissions after cardiopulmonary resuscitation
* Severe immunosuppression other than steroid use
* stem-cell transplant recipients
* solid organ transplant patients
* HIV infection with a CD4 count of less than 200 cells/mm3
* Neutropenia with less than 500 neutrophils/mm3
* Patients on ABs within 72 hours before inclusion
* Patients in pregnancy or breastfeeding. Women of childbearing age will be screened by a urine pregnancy test before inclusion in the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Semmelweis University

OTHER

Sponsor Role lead

Responsible Party

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Dr. Papp Márton

co-head of the unit

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Nikolett Kiss

Role: STUDY_CHAIR

Semmelweis University

László Zubek

Role: STUDY_CHAIR

Semmelweis University

Caner Turan

Role: STUDY_CHAIR

Semmelweis University

Dilan M. Karim

Role: STUDY_CHAIR

Semmelweis University

Locations

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Saint Margaret's Hospital

Budapest, , Hungary

Site Status NOT_YET_RECRUITING

Semmelweis University, Department of Intensive Therapy

Budapest, , Hungary

Site Status RECRUITING

Countries

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Hungary

Central Contacts

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Márton Papp

Role: CONTACT

+36206663224

Zsolt Molnár

Role: CONTACT

+36303026668

Facility Contacts

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Lóránt Csiki

Role: primary

+36305647189

Márton Papp

Role: primary

+36206663224

Dilan M. Karim

Role: backup

+36207752933

References

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Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS, Angus DC, Rubenfeld GD, Singer M; Sepsis Definitions Task Force. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):775-87. doi: 10.1001/jama.2016.0289.

Reference Type BACKGROUND
PMID: 26903336 (View on PubMed)

Tsangaris I, Plachouras D, Kavatha D, Gourgoulis GM, Tsantes A, Kopterides P, Tsaknis G, Dimopoulou I, Orfanos S, Giamarellos-Bourboulis E, Giamarellou H, Armaganidis A. Diagnostic and prognostic value of procalcitonin among febrile critically ill patients with prolonged ICU stay. BMC Infect Dis. 2009 Dec 22;9:213. doi: 10.1186/1471-2334-9-213.

Reference Type BACKGROUND
PMID: 20028533 (View on PubMed)

Trasy D, Tanczos K, Nemeth M, Hankovszky P, Lovas A, Mikor A, Hajdu E, Osztroluczki A, Fazakas J, Molnar Z. Delta Procalcitonin Is a Better Indicator of Infection Than Absolute Procalcitonin Values in Critically Ill Patients: A Prospective Observational Study. J Immunol Res. 2016;2016:3530752. doi: 10.1155/2016/3530752. Epub 2016 Aug 15.

Reference Type BACKGROUND
PMID: 27597981 (View on PubMed)

Szakmany T, Molnar Z. Procalcitonin levels do not predict mortality following major abdominal surgery. Can J Anaesth. 2003 Dec;50(10):1082-3. doi: 10.1007/BF03018387. No abstract available.

Reference Type BACKGROUND
PMID: 14656802 (View on PubMed)

Trasy D, Tanczos K, Nemeth M, Hankovszky P, Lovas A, Mikor A, Laszlo I, Hajdu E, Osztroluczki A, Fazakas J, Molnar Z; EProK study group. Early procalcitonin kinetics and appropriateness of empirical antimicrobial therapy in critically ill patients: A prospective observational study. J Crit Care. 2016 Aug;34:50-5. doi: 10.1016/j.jcrc.2016.04.007. Epub 2016 Apr 13.

Reference Type BACKGROUND
PMID: 27288610 (View on PubMed)

Najafi A, Khodadadian A, Sanatkar M, Shariat Moharari R, Etezadi F, Ahmadi A, Imani F, Khajavi MR. The Comparison of Procalcitonin Guidance Administer Antibiotics with Empiric Antibiotic Therapy in Critically Ill Patients Admitted in Intensive Care Unit. Acta Med Iran. 2015;53(9):562-7.

Reference Type BACKGROUND
PMID: 26553084 (View on PubMed)

Layios N, Lambermont B, Canivet JL, Morimont P, Preiser JC, Garweg C, Ledoux D, Frippiat F, Piret S, Giot JB, Wiesen P, Meuris C, Massion P, Leonard P, Nys M, Lancellotti P, Chapelle JP, Damas P. Procalcitonin usefulness for the initiation of antibiotic treatment in intensive care unit patients. Crit Care Med. 2012 Aug;40(8):2304-9. doi: 10.1097/CCM.0b013e318251517a.

Reference Type BACKGROUND
PMID: 22809906 (View on PubMed)

Jensen JU, Hein L, Lundgren B, Bestle MH, Mohr TT, Andersen MH, Thornberg KJ, Loken J, Steensen M, Fox Z, Tousi H, Soe-Jensen P, Lauritsen AO, Strange D, Petersen PL, Reiter N, Hestad S, Thormar K, Fjeldborg P, Larsen KM, Drenck NE, Ostergaard C, Kjaer J, Grarup J, Lundgren JD; Procalcitonin And Survival Study (PASS) Group. Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial. Crit Care Med. 2011 Sep;39(9):2048-58. doi: 10.1097/CCM.0b013e31821e8791.

Reference Type BACKGROUND
PMID: 21572328 (View on PubMed)

Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Hylander Moller M, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021 Nov 1;49(11):e1063-e1143. doi: 10.1097/CCM.0000000000005337. No abstract available.

Reference Type BACKGROUND
PMID: 34605781 (View on PubMed)

Papp M, Kiss N, Baka M, Trasy D, Zubek L, Fehervari P, Harnos A, Turan C, Hegyi P, Molnar Z. Procalcitonin-guided antibiotic therapy may shorten length of treatment and may improve survival-a systematic review and meta-analysis. Crit Care. 2023 Oct 13;27(1):394. doi: 10.1186/s13054-023-04677-2.

Reference Type BACKGROUND
PMID: 37833778 (View on PubMed)

de Kraker ME, Stewardson AJ, Harbarth S. Will 10 Million People Die a Year due to Antimicrobial Resistance by 2050? PLoS Med. 2016 Nov 29;13(11):e1002184. doi: 10.1371/journal.pmed.1002184. eCollection 2016 Nov.

Reference Type BACKGROUND
PMID: 27898664 (View on PubMed)

Montravers P, Dupont H, Gauzit R, Veber B, Bedos JP, Lepape A; Club d'Infectiologie en Anesthesie-Reanimation Study Group. Strategies of initiation and streamlining of antibiotic therapy in 41 French intensive care units. Crit Care. 2011;15(1):R17. doi: 10.1186/cc9961. Epub 2011 Jan 13.

Reference Type BACKGROUND
PMID: 21232098 (View on PubMed)

Klein Klouwenberg PM, Cremer OL, van Vught LA, Ong DS, Frencken JF, Schultz MJ, Bonten MJ, van der Poll T. Likelihood of infection in patients with presumed sepsis at the time of intensive care unit admission: a cohort study. Crit Care. 2015 Sep 7;19(1):319. doi: 10.1186/s13054-015-1035-1.

Reference Type BACKGROUND
PMID: 26346055 (View on PubMed)

Vincent JL, Sakr Y, Singer M, Martin-Loeches I, Machado FR, Marshall JC, Finfer S, Pelosi P, Brazzi L, Aditianingsih D, Timsit JF, Du B, Wittebole X, Maca J, Kannan S, Gorordo-Delsol LA, De Waele JJ, Mehta Y, Bonten MJM, Khanna AK, Kollef M, Human M, Angus DC; EPIC III Investigators. Prevalence and Outcomes of Infection Among Patients in Intensive Care Units in 2017. JAMA. 2020 Apr 21;323(15):1478-1487. doi: 10.1001/jama.2020.2717.

Reference Type BACKGROUND
PMID: 32207816 (View on PubMed)

Other Identifiers

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BM/20019- 1/2025

Identifier Type: -

Identifier Source: org_study_id

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