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NCT Number: NCT06960044

Procalcitonin Aided Antimicrobial Therapy vs Standard of Care

Antibiotic resistance is driven by overuse, especially for viral respiratory infections. Procalcitonin (PCT), a biomarker for bacterial infections, helps guide antibiotic therapy more precisely, reducing unnecessary use and improving outcomes. Studies, including large trials and economic models across several countries, show PCT-guided treatment lowers mortality, antibiotic exposure, therapy duration and related complications, potentially reducing hospital costs despite initial testing expenses.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

Antibiotic resistance (ABR) poses a significant threat to global health and is largely driven by the overuse of antibiotics, particularly for acute respiratory tract infections (ARTIs), which are mostly viral. Despite this, antibiotics are frequently prescribed, often for unnecessarily long durations due to the lack of reliable markers indicating illness resolution. This has led to an interest in using biomarkers like procalcitonin (PCT) to guide antibiotic therapy more accurately.

PCT is a precursor of the hormone calcitonin and increases significantly in the presence of bacterial infections, offering a promising tool for distinguishing bacterial from viral infections and for monitoring infection progression and response to treatment. It rises within hours of infection onset, peaks by day two, and decreases with recovery, making it useful for deciding when to start or stop antibiotics.

Clinical studies, including the large PRORATA randomized controlled trial, have demonstrated that PCT-guided antibiotic protocols are safe and effective in reducing antibiotic use without compromising patient outcomes. A Cochrane review further supported this, showing that PCT-guided therapy reduces mortality, antibiotic consumption, and antibiotic-related adverse effects in patients with ARTIs.

However, PCT testing has yet to be widely adopted in hospitals due to concerns about its cost-effectiveness and implementation challenges. To address these concerns, a series of health economic evaluations have been carried out: they assess the clinical and economic impact of PCT-guided therapy, particularly its role in reducing complications such as ABR and Clostridium difficile infections (CDI).

Findings consistently show that PCT-guided antibiotic therapy not only improves patient outcomes but also reduces direct healthcare costs when compared to standard care. Recent modeling incorporating RWE from a U.S. hospital further confirmed these benefits in real-world settings, strengthening the case for broader adoption of PCT in hospital-based antibiotic stewardship programs.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • age ≥18 years;
  • clinical and instrumental diagnosis of LRTI consistent with bacterial origin and requiring antimicrobial treatment;
  • patient hospitalized in Internal Medicine, Geriatrics, Infectious Disease unit, Pneumology, Semi Intensive Care unit, ICU, Emergency Medicine;
  • informed consent provided by the patient.

Exclusion criteria

  • age < 18 years;
  • lack of informed consent;
  • severe immunosuppression (other than related to corticosteroid use);
  • concomitant diagnosis of other infections requiring long term antimicrobial therapy (i.e. endocarditis, osteomyelitis)

Treatment and study plan

Procalcitonin-guided antibiotic management

Procedure

After the randomization, PCT plasma concentration will be dosed and repeated every 24 hours and antimicrobial treatment will be withdrawn as soon as the PCT value will decrease > 80% of peak value or will fall below 0.25 ng/mL. Patients with a normal baseline PCT value (below 0.25 ng/mL) will start the antimicrobial therapy, as clinically appropriate and PCT plasma concentration will be repeated every 24 hours, as indicated in the protocol. The antimicrobial agents will be managed according to the clinical and radiological evolution of the LRTI.

Standard of care

Procedure

Patients assigned to the control group will be treated according to the best standard of care and PCT will not be evaluated for the whole duration of the study.

Primary outcomes

  1. Duration of antimicrobial treatment

    Time frame: Periprocedural

    Measure of the antimicrobial treatment duration in days

Secondary outcomes

  1. Length of hospital stay

    Time frame: Periprocedural

    Measure of the hospital stay in days

  2. Sequential Organ Failure Assessment

    Time frame: At baseline and every 24 hours

    Assessment of clinical outcome with the SOFA Score, based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Score ranges from 0 (best) to 24 (worst) points.

  3. Quick Sequential Organ Failure Assessment

    Time frame: At baseline

    Assessment of clinical outcome with the qSOFA Score, a simplified version of the SOFA Score. Score ranges from 0 (best) to 3 (worst) points.

  4. National Early Warning Score

    Time frame: At baseline and every 24 hours

    Assessment of clinical outcome with the NEWS Score, which identifies three alert levels with their specific clinical responses depending on the degree of criticality in relation to the final score derived (from 0 (code green) to 6 (code red)).

  5. Incidence of Clostridium difficile infections (CDI)

    Time frame: Periprocedural

    Measure of the incidence of CDI with stool tests and GHD tests

  6. Incidence of multi-drug resistance (MDR) infections

    Time frame: In the next 30 days after the baseline

    Measure of the incidence of MDR infections

  7. Mortality

    Time frame: During the study, 4 weeks and 3 months from baseline

    Mortality evaluation

  8. Costs

    Time frame: Periprocedural

    Evaluation of the costs associated with antibiotic therapy and hospitalization, relative to ABR per patient with LRTI and relative to CDI per patient with LRTI

Study contacts

Contact information is provided by the study sponsor or research team.

Prof. Luigi Mario Castello

CONTACT

[email protected]

0131206893

Sponsors and collaborators

Lead sponsor

Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria

Other

Collaborators

  • Thermo Fisher Scientific FS

Registry information

Official study title

Procalcitonin Aided Antimicrobial Therapy vs Standard of Care: a Randomized Prospective Clinical Trial

Acronym: PCT

Important dates

Study start
2025
Primary completion
2026
Study completion
2027
First posted
May 7, 2025
Registry last updated
May 7, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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