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

NCT07211620 | Recruiting DMC

• 1 other identifier: BM/20019- 1/2025
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Infection; Sepsis

Keywords

procalcitonin; bacterial infection; antibiotics; kinetics

Outcome Measures

Primary Outcomes (1)

• Rate of unnecessary antibiotic therapy

  The number of unjustified antibiotic therapies divided by the number of all therapies.

  From date of enrollment until 72 hours.

Secondary Outcomes (11)

• Organ-support free days

  From date of enrollment until the date of disharge of the patient from the ICU or the date of patient's death from any cause, whichever came first, assessed up to 6 months.

• Lenght of stay at the intensive care unit

  From date of enrollment until the date of discharge of patient from the ICU or the date of patient's death from any cause, whichever came first, assessed up to 6 months.

• Length of stay in hospital

  From date of enrollment until the date of hospital discharge of the patient or the date of patient's death from any cause, whichever came first, assessed up to 6 months.

• Duration of mechanical ventilation

  From date of enrollment until date of ICU discharge of the patient or date of patient's death from any cause, whichever came first, asessed up to 6 months.

• Duration of renal replacement therapy

  From date of enrollment until date of hospital discharge of the patient or date of patient's death from any cause, whichever came first, assessed up to 6 months.

Study Arms (2)

Kinetics

EXPERIMENTAL

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.

Other: Kinetics

Absolute

EXPERIMENTAL

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

Other: Absolute

Interventions

Kinetics 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.

Kinetics

Absolute OTHER

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

Absolute

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Semmelweis University: lead

Study Sites (2)

Saint Margaret's Hospital

Budapest, 1032, Hungary

NOT YET RECRUITING

Semmelweis University, Department of Intensive Therapy

Budapest, 1082, Hungary

RECRUITING

Related Publications (14)

• 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.

  PMID: 26903336 BACKGROUND

• 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.

  PMID: 20028533 BACKGROUND

• 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.

  PMID: 27597981 BACKGROUND

• 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.

  PMID: 14656802 BACKGROUND

• 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.

  PMID: 27288610 BACKGROUND

• 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.

  PMID: 26553084 BACKGROUND

• 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.

  PMID: 22809906 BACKGROUND

• 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.

  PMID: 21572328 BACKGROUND

• 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.

  PMID: 34605781 BACKGROUND

• 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.

  PMID: 37833778 BACKGROUND

• 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.

  PMID: 27898664 BACKGROUND

• 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.

  PMID: 21232098 BACKGROUND

• 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.

  PMID: 26346055 BACKGROUND

• 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.

  PMID: 32207816 BACKGROUND

MeSH Terms

Conditions

Infections; Sepsis; Bacterial Infections

Interventions

Kinetics

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Mechanical Phenomena; Physical Phenomena; Biochemical Phenomena; Chemical Phenomena

Study Officials

• Nikolett Kiss

  Semmelweis University

  STUDY CHAIR

• László Zubek

  Semmelweis University

  STUDY CHAIR

• Caner Turan

  Semmelweis University

  STUDY CHAIR

• Dilan M. Karim

  Semmelweis University

  STUDY CHAIR

Central Study Contacts

Márton Papp

CONTACT

+36206663224; papp.marton@semmelweis.hu

Zsolt Molnár

CONTACT

+36303026668; molnar.zsolt1@semmelweis.hu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Nurses
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: co-head of the unit

Study Record Dates

• First Submitted: September 21, 2025
• First Posted: October 8, 2025
• Study Start: November 6, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: January 9, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

HU (2)