Reduction of Antibiotic Therapy by Biomakers in Patients With CAP Episodes (REDUCE Study)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate two different treatment strategies in patients admitted to hospital with Community Acquired Pneumonia. The investigators hypothesize treatment according to both procalcitonin (PCT) and C-reactive protein (CRP) will be effective in reducing the length of antibiotic treatment.

Official Title
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Reduction of Antibiotic Therapy by Biomakers in Patients With CAP Episodes (REDUCE Study)

Conditions
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Community Acquired Pneumonia

Intervention / Treatment
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* Drug: Discontinuation of treatment according to CRP levels
* Drug: Discontinuation of treatment according to PCT levels
* Drug: Treatment according to current guidelines


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients with a diagnosis of CAP and all criteria listed below: Age 18 or above, no upper age limit will be employed. Patients must require hospitalisation. Clinical presentation of an acute illness with one or more of the following symptoms: Temperature ≥ 38.0 ⁰C (100.4°F) Dyspnoea Cough (with or without expectoration of sputum) Chest pain Malaise or fatigue Myalgia Gastro-intestinal symptoms Rales, rhonchi or wheezing Egophony or bronchial breath sounds New consolidation(s) on the chest radiograph. Written informed consent obtained. (Pre-event) Life expectancy > 30 days Exclusion Criteria: Subjects presenting with any of the following will not be included in the study: (Severe) immunosuppression (e.g. HIV infection, chemotherapy, use of immunosuppressants). Active neoplastic disease. Obstruction pneumonia (e.g. from lung cancer). Aspiration pneumonia. Pneumonia that developed within 8 days after hospital discharge. Unable and/or unlikely to comprehend and/or follow the protocol. Pregnant and/or lactating women. Other infection that requires treatment with antibiotics

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 |
| --- | --- |
| Active Comparator: Common clinical practice<br>Treatment according to current guidelines. Often a 7 day course of antibiotics. Initial treatment should be broad spectrum antibiotics and can be narrowed down if a specific pathogen is identified. | Drug: Treatment according to current guidelines<br>* Often a 7 days course of antibiotics, treatment may be extended if the attending physician deems it necessary.<br>* Other names: Small spectrum antibiotics;|
| Experimental: CRP-guided treatment<br>Treatment according to CRP levels. Patients will be started on broad spectrum antibiotics for at least 3 days, treatment can be switched to small-spectrum antibiotics if a specific pathogen is identified. From day 4 to 7 daily blood tests will be performed in order to evaluate whether or not treatment can be discontinued. If treatment is discontinued, no more blood tests will be performed. | Drug: Discontinuation of treatment according to CRP levels<br>* The cutoff point is a CRP below 100 mg/L and a reduction to 50% of the initial value.<br>* Other names: Small spectrum antibiotics;|
| Experimental: PCT guided treatment<br>Treatment according to PCT levels. Patients will be started on broad spectrum antibiotics for at least 3 days, treatment can be switched to small-spectrum antibiotics if a specific pathogen is identified. From day 4 to 7 daily blood tests will be performed in order to evaluate whether or not treatment can be discontinued. If treatment is discontinued, no more blood tests will be performed. | Drug: Discontinuation of treatment according to PCT levels<br>* The cutoff point is a PCT below 0.25 mcg/L or a reduction to 10% of the initial value.<br>* Other names: Small spectrum antibiotics;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of antibiotic treatment |  | End of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of stay |  | End of the study | 
| Clinical response | Cure - resolution or improvement of symptoms and clinical signs related to pneumonia without the need for additional or alternative antibiotic therapy Failure - persistence or progression of all signs and symptoms of the acute process after randomisation or the development of a new pulmonary or extrapulmonary respiratory tract infection, or the progression of abnormalities on chest radiograph after randomisation, or death due to pneumonia, or the inability to complete the study owing to adverse events Indeterminate - patient receives less than 80% of the study drug for reasons other than clinical failure, a concomitant infection outside the respiratory tract requiring antibiotic treatment, lost to follow-up, or death unrelated to the primary diagnosis. | End of the study | 
| 30-day mortality | All cause | End of the study, periodically by the DSMB | 
| Time to clinical stability | Patients are considered clinically stable if they fulfill all of these criteria: Temperature equal to or below 37.8 degrees celsius, heart rate equal to or below 100 beats per minute, respiratory rate equal to or below 24 breaths per minute, systolic blood pressure equal to or above 90 mmHg, arterial oxygen saturation equal to or above 90 percent or pO2 equal to or above 60 mmHg on room air, ability to maintain oral intake, normal mental status. | End of the study | 
| Relapse rate |  | End of the study |