Biomarker Guided Antibiotic Treatment in Community-Acquired Pneumonia

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy of C-reactive protein and procalcitonin based guidelines versus standard of care to reduce duration of antibiotic exposure in patients hospitalized with community acquired pneumonia.

Detailed Description
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BIO-CAP is a prospective randomized intervention study which aims to evaluate the efficacy of C-reactive protein (CRP) based guidelines and procalcitonin (PCT) based guidelines to reduce duration of antibiotic exposure in adult patients hospitalized with community-acquired pneumonia (CAP) compared to standard-of-care. Hypothesis: the duration of antibiotic exposure can be reduced when a biomarker algorithm - in addition to standard of care - is used to stop antibiotic treatment. 1) CRP based guidelines can reduce duration of antibiotic exposure equally to procalcitonin based guidelines and 2) Either of these two biomarker algorithms ( CRP or PCT) are superior compared to standard of care. Sample size. Preconditions: significance level (α) 5 % and power (β) 80 %. Test: unpaired T-test. Mean treatment time 11 days (SD 5) in this population. Relevant detection limit defined at 2 days. The bonferroni correction has been used to correct for the fact that 2 primary analysis will be performed, why α = 0.005/2 = 0.025. Estimated 100 patient in each arm, thus n = 300. Site monitoring and auditing. The study is monitored by the unit for Good Clinical Practice, Bispebjerg Hospital, Denmark.

Official Title
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Biomarker Guided Antibiotic Treatment in Community-Acquired Pneumonia

Conditions
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Community Acquired Pneumonia

Intervention / Treatment
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* Behavioral: CRP-algorithm
* Behavioral: PCT-algorithm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18 years of age or older admitted to hospital with community acquired pneumonia defined as a new infiltrate on x-ray and at least one of the following; cough, expectoration, dyspnea, fever and pathological lung-auscultation. Not admitted to hospital within the last 14 days The patients has been prescribed antibiotic treatment for pneumonia The patient can comprehend the written and verbal information and has provided written consent. Exclusion Criteria: Patient are unable to give written consent or patient does not understand the Danish language. Active pulmonary tuberculosis Severe immunosuppression determined by the treating physician (i.e. treatment with highdose corticosteroid for more than 2 weeks, chemotherapy and neutropenia with neutrophils < 0.5x109/l, ongoing treatment with biological drugs, chronic HIV-infection with CD4 cell count < 350 mio./l, immunosuppression after organ transplantation). Pregnancy and breastfeeding Patients admitted to hospital and treated against their will. Terminal ill patients where active treatment is stopped within the first 48 hours of admission. Patients who are, from the date of inclusion, prescribed antibiotic treatment for more than 3 days on a different indication than pneumonia.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Patients are treated according to current local guidelines on antibiotic treatment for CAP. | |
| Experimental: CRP<br>Patients are treated according to the CRP-algorithm. CRP is measured daily. Antibiotic treatment is stopped when CRP reach threshold value. | Behavioral: CRP-algorithm<br>* a strategy based on CRP guided antibiotic stewardship<br>|
| Experimental: PCT<br>Patients are treated according to the PCT-algorithm. PCT is measured daily. Antibiotic treatment is stopped when PCT reach threshold value. | Behavioral: PCT-algorithm<br>* a strategy based on PCT guided antibiotic stewardship<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of antibiotic treatment | Number of days in antibiotic treatment for pneumonia | 30 days from inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30 day mortality | Number of patients who die within 30 days. | 30 days from inclusion | 
| Relapse | Number of patients who are readmitted due to pneumonia or resumed treatment for pneumonia. | 30 days from inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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C-reactive protein, Procalcitonin, Community-acquired pneumonia, Antibiotic stewardship