Procalcitonin as a Marker of Antibiotic Therapy in Patients With Lower Respiratory Tract Infections

Procalcitonin as a Marker of Antibiotic Therapy in Patients With Lower Respiratory Tract Infections. Can Measurement of Procalcitonin Reduce the Use of Antibiotics?

The purpose of this study is to investigate weather or not the use of a procalcitonin(PCT)-based treatment in the daily clinical work could lower the consumption of antibiotics in patients with lower respiratory tract infections.

Study Overview

• Status: Unknown
• Conditions: Pneumonia; Acute Exacerbation of Chronic Obstructive Airways Disease
• Intervention / Treatment: Other: PCT-level; Behavioral: Antibiotic treatment based on PCT-level

Detailed Description

An increasing amount of antibiotics are being consumed and along with the increased resistance they carry along, they pose an increasing problem for the health sector. A method to decrease the use of antibiotics is highly desirable and of great importance in order to halt the spread of multi-resistant bacteria that is becoming an increasing problem in Denmark.

Lower respiratory tract infections such as pneumonia and acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are frequent reasons for patient contact in both the primary and secondary sectors. Identifying which patients that could benefit from treatment with antibiotics is a great challenge to the health sector. This is why patients often are treated with antibiotics if there is a mere suspicion of the above-mentioned disorders, even if they are not proved for certain.

An increasing amount of data suggests that procalcitonin (PCT) could serve as a possible marker of respiratory tract infections caused by bacteria. Alongside the conventional clinical parameters, the level of PCT is regarded as a promising means to decide whether to treat with antibiotics and how long such a treatment should endure. When an infection is under control by the immune system of the individual or by treatment with antibiotics, the level of PCT will diminish by 50% on a daily basis. Accordingly, a decline in the PCT levels should indicate a favorable response to antibiotic treatment. Therefore there is a need to further investigate if the PCT levels can be used, in the everyday clinic, to diagnose patients with pneumonia or AECOPD caused by bacteria and if this could have an effect on the use of antibiotics, thus optimizing the treatment of the patients.

The purpose of this research project is to compare the amount of antibiotics consumed using standard treatment and treatment based on the PCT levels of patients with lower respiratory tract infections, respectively.

With the research at hand, a clarification of whether a measurement of PCT can serve as a diagnostic tool to distinguish between bacterial and non-bacterial infections in patients that are suspected of having pneumonia or AECOPD is desirable. In extension, this study wants to clarify if the PCT levels can indicate when a potential antibiotic treatment should be initiated and if the use of a PCT-based treatment in the daily clinical work could lower the consumption of antibiotics.

The hypothesis is that PCT will be increased (≥0.25 µg/l and ≥0.10 µg/l for pneumonia and AECOPD respectively) in lower respiratory tract infections caused by bacteria, whereas PCT should only be slightly increased in non-bacterial lower respiratory tract infections if at all. It is expected that using a PCT-based treatment in lower respiratory tract infections could lower the consumption of antibiotics, while at the same time it should not prove a greater health risk to patients than by using a standard treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 55
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Holbæk, Denmark, 4300
    • Holbæk Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Hospitalized in Holbæk Hospital
• Clinical and paraclinical signs of pneumonia and/or AECOPD.

Exclusion Criteria:

• Unable to hand over written consent.
• Terminal patients.
• Patients with known abscess in the lungs and/or emphysema.
• Patients who have received treatment with strong doses (>5mg/day) of biotin (vitamin B7 og B8) within the last eight hours.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Antibiotic treatment based on PCT-level; Information regarding the PCT-levels in the intervention group is available to the treating doctor and the test subjects are randomized for treatment based on the level of PCT (PCT algorithm). With a PCT ≥0.25 µg/l and ≥0.10 µg/l for pneumonia and AECOPD respectively antibiotic treatment is advised to be started.	Other: PCT-level; PCT-level is available to the treating doctor.; Behavioral: Antibiotic treatment based on PCT-level; PCT-level is available to the treating doctor and the decision whether or not to treat with antibiotic is based on the level of PCT. The type of antibiotic chosen to treat is based on the existing antibiotic treatment guidelines of Holbaek Hospital and includes the antibiotics listed above.; Other Names: Piperacillin/Tazobactam; Clarithromycin; Ciprofloxacin; Avelox®; Azithromycin; Benzylpenicillin; Bioclavid®; Cefuroxim; Primcillin; Vepicombin®; Zinacef®
No Intervention: Control; Test subjects randomized for standard treatment (control group) are treated in accordance with the existing treatment guidelines of Holbaek Hospital. PCT-level will be measured but the treating doctor has no access to the result.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Days of antibiotic treatment	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks, and up to 2 weeks after discharge.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numbers of days admitted	Numbers of days admitted from the day og enrollment in the study to the day of discharge.	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients with low PCT-level	Numbers of patients with a PCT-level ≤0,1 µm/L and ≤0,25 µm/L in AECOPD and pneumonia respectively who gets treated with antibiotics during their hospitalization.	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks.
Recurrence within 30 days after discharge	Numbers of patients with recurrence of AECOPD or pneumonia within 30 days after discharge.	From 1 to 30 days after discharge
Type of antibiotics	Antibiotics used to treat the enrolled patients (name, i.v. or p.o.)	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks, and up to 2 weeks after discharge.
Death and adverse events in the two treatment groups	Death and adverse events in the two treatment groups meaning: Death by any cause; Complications in connection with lower respiratory tract infections (empyema, abscess); Severe complications from treatment with antibiotics (anaphylactic shock, rash); Admission to intensive care unit; Readmission within 30 days	Participants will be followed for the duration of hospital stay, an expected average of 2 weeks, and up to 30 days after discharge.

Collaborators and Investigators

• Sponsor: Holbaek Sygehus
• Collaborators: Aase and Ejnar Danielsens Foundation; Region Sjælland
• Investigators: Study Director: Hans Ibsen, M.D., D.M.Sc, Holbaek Sygehus

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Anticipated): August 1, 2014
• Study Completion (Anticipated): September 1, 2014

Study Registration Dates

• First Submitted: June 17, 2014
• First Submitted That Met QC Criteria: June 20, 2014
• First Posted (Estimate): June 24, 2014

Study Record Updates

• Last Update Posted (Estimate): August 15, 2014
• Last Update Submitted That Met QC Criteria: August 14, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Procalcitonin; Antibiotic therapy; Lower respiratory tract diseases
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; beta-Lactamase Inhibitors; Anti-Bacterial Agents; Ciprofloxacin; Clarithromycin; Azithromycin; Piperacillin; Penicillin G; Tazobactam; Piperacillin, Tazobactam Drug Combination
• Other Study ID Numbers: SJ-342; SJ-RO-01, j.nr. 12-000179 (Registry Identifier: Region Sjaelland, Datatilsynet)