Research Title: Efficacy and Safety of Point- Of-care Procalcitonin Test to Reduce Antibiotic Exposure in VAP

Mohd Zulfakar Mazlan, MBBS

Status: Completed

Conditions: Ventilator Associated Pneumonia

Treatments: Diagnostic Test: PCT-guided group

Study type: Interventional

Funder types: Other

Identifiers

NCT03982667

USMalaysia

Details and patient eligibility

About

Several studies have shown that PCT guidance can reduce the duration of antibiotic treatment for patients with bacterial infections in the ICU, without compromising the safety outcomes. However PCT is known to be more costly than standard biomarkers that commonly use in our ICU setup. This remain the main challenge for us whether by monitoring the PCT level, it can reduce both the duration of antibiotic simultaneously reduce the total cost of the treatment for the patients. A local study addressing efficacy, safety and cost analysis of PCT-guided antibiotic therapy in severe pneumonia patients is therefore warranted. Until the results from a local study become available, the utility of PCT to guide antibiotic duration in our patient population cannot be recommended.

Full description

Pneumonia remains one of the major cause of morbidity and mortality in critically ill patients in the intensive care unit (ICU) worldwide. In Malaysia, according to the Malaysian Registry of Intensive Care 2016, pneumonia was among the four (5.7%) most common diagnosis leading to admission to ICU. In many scenario, pneumonia associated with severe sepsis either as single source of sepsis or in combination with other source of infection which carry mortality mortality reported 53.4% 1. Timely, appropriate and adequate antibiotic therapy is of paramount importance in the critically ill patients with severe pneumonia. However, overly long antibiotic treatment is undesirable because of side effects, increasing antibiotic resistance2 and financial burden to patient and Malaysia Healthcare.

Antibiotic remain the main weapon to combat pneumonia. Nevertheless, rampant use of antibiotic without specific indicator is vain. Hence, with the latest technology, physicians not only rely on clinical improvement but also specific biomarkers for resolution of sepsis which might assist the ICU physicians in making decisions on antibiotic therapy on an individual basis.

Commonest used biomarkers for this purpose include leucocyte count and C-reactive protein (CRP). These biomarkers are sensitive but not specific. Procalcitonin (PCT) however has been advocated as a biomarker with a better specificity and sensitivity for diagnosis and follow-up of severe bacterial infections.

PCT is the prohormone of calcitonin. It consists of about 116 amino-acids. The locus of formation in classical pathway is the C-cells of the thyroid. In case of bacterial infection, PCT is formed in all tissues via an alternative pathway. Linscheid et al. 2004 described, in case of bacterial infection two mechanisms of synthesis are at work. At first cytokine-stimulated adherent monocytes release PCT in low quantities. This synthesis is limited. But it plays an important role in the initiation of PCT synthesis in storage tissues of humans. This PCT burst is initiated in all storage tissues (>18h). PCT is a perfect tool to differentiate between viral and bacterial infections (e.g. Gendrel et al. 1999). This is why in septic patients extremely high concentrations of PCT were found in the plasma (about 100,000-fold of the physiological concentration in healthy subjects).

Enrollment: 100 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age 18 years and above; and
• Admitted to the ICU; and
• Receive their first dose of antibiotics no longer than 24 h before inclusion to the trial for an assumed or proven bacterial infection.
• Treated as Ventilator Associated Pneumonia (VAP)

Exclusion criteria

• Systemic antibiotics as prophylaxis only
• Antibiotics solely as part of selective decontamination of the digestive tract
• Prolonged therapy (eg, endocarditis)
• Expected ICU stay of less than 24 h
• Severe immunosuppression
• Severe infections due to non-bacterial causes
• Previously been enrolled in the study

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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100 participants in 2 patient groups

PCT group

Experimental group

Description:

For patients randomly assigned to the PCT-guided group, measurements of serum PCT concentrations (Day 1, 3, 7, and 9) will be taken and made available to the attending physicians. This means 3 ml of whole blood will be sampled from the arterial line of the patients for each measurement the serum PCT in plain tubes. The samples will be immediately assayed for the PCT measurement using the available device and the results will be ready in next 30 minutes after running the system.

Treatment:

Diagnostic Test: PCT-guided group

Standard-of-care group

No Intervention group