CRP-guided Antibiotic Treatment in COPD Exacerbations Admitted to the Hospital
CRP-guided Antibiotic Treatment in COPD Exacerbations Admitted to the Hospital
Rationale: Acute exacerbations are key events in chronic obstructive pulmonary disease
 (COPD), resulting in poorer quality of life. Causes include irritants, viruses and bacterial
 pathogens. These exacerbations are often treated with a combination of corticosteroids,
 bronchodilators and antibiotics, but the benefit of antibiotic therapy remains controversial.
 Several trials studying antibiotic treatment in AECOPD showed conflicting data, with several
 large studies failing to demonstrate superiority of antibiotic therapy over placebo. Other
 trials indicated that antibiotic therapy is effective in patients who have at least two of
 the following symptoms: increased dyspnoea, increased sputum volume and increased sputum
 purulence. Ever since sputum purulence has been used as a predictive marker in AECOPD, a
 strategy that has been integrated in the GOLD guideline for treatment of AECOPD. However, the
 color of sputum reported by patients is not always reliable and inspection of sputum is not
 always possible. Several serum biomarkers such as C-reactive protein (CRP) and procalcitonin
 (PCT) are now available. In a recent trial of doxycycline in addition to systemic
 corticosteroids for patients hospitalized with AECOPD we found that CRP might be valuable as
 a marker predictive of response to antibiotic treatment in AECOPD.
Objective: CRP-guided antibiotic therapy will be compared with standard antibiotic therapy in
 AECOPD. Our aim is that CRP guided therapy will lead to 20% reduction in antibiotic
 consumption.

 Study design: randomized controlled intervention trial Study population: Hospitalised COPD
 patients with acute exacerbation. Intervention (if applicable): Patients with type 1 and 2
 exacerbation will be assigned to either CRP guided therapy or antibiotic therapy according to
 GOLD guidelines.

 Main study parameters/endpoints: The main endpoint of the study is the reduction in
 antibiotic consumption. Furthermore, the real incidence of infiltrates in AECOPD with fever
 will be studied. As secondary outcome the objectives length of hospitalization, time to
 treatment failure within 30-days and time to next exacerbation will be assessed. The relation
 between the level of biomarkers the presence of infiltrates on the HRCT will be investigated.

 Subjective improvement in symptoms will be measured by symptoms (VAS-LRTI) and quality of
 life will be assessed by St George's Respiratory Questionnaire. Finally, adverse effects of
 the antibiotic treatment will be recorded.

 In order to observe a significant difference of antibiotic consumption, 60% in standard
 antibiotic group and 40% in CRP guided antibiotic group, with a power of 0.8, a total of 110
 patients have to be assigned by randomisation to each group.

 Nature and extent of the burden and risks associated with participation, benefit and group
 relatedness: Patients in both treatment arms will receive a non-experimental treatment. Both
 treatment options are recognized as part of standard care. The burden associated with
 participation is limited to a total of 3 visits to the hospital and phone call for data
 assessment at regular follow-up. There are no specific risks involved in participating. Less
 adverse effects may be beneficially for the patient.
Inclusion Criteria:

 -  Age 40 or over. No upper age limit will be employed.

 -  Written informed consent obtained.

 -  AECOPD according to the GOLD guideline. An exacerbation of COPD is defined as an event
 in the natural course of the disease characterized by a change in the patient's
 baseline dyspnoea, cough, and/or sputum that is beyond normal day-to-day variations,
 is acute in onset, and may warrant a change in regular medication in a patient with
 underlying COPD.

 -  Criteria for hospital admission according to the GOLD: marked increase in symptoms
 (i.e. resting dyspnoea), severe underlying COPD, onset of new physical signs
 (cyanosis, edema), failure to respond to initial medical management, significant co
 morbidities, frequent exacerbations, newly occurring arrhythmias, diagnostic
 uncertainty.

 -  Former of current smoker with a minimum smoking history of 10 pack years.

 -  Patients have to be capable of ingesting oral medication.

 -  Patients have to be mentally capable of participating in the study (able to complete
 questionnaires and perform lung function tests).

 -  Life expectancy ≥ 30 days.

 Exclusion Criteria:

 -  Pregnant or lactating women, or women of childbearing age not using an acceptable
 method of contraception.

 -  Pretreatment with corticosteroids (cumulative dose >210 mg) for the present
 exacerbation.

 -  Progression or new radiographic abnormalities on the chest X-ray or CT scan compatible
 with pneumonia.

 -  bronchiectasis (HRCT confirmed).

 -  Cystic fibrosis.

 -  Tuberculosis.

 -  Immunodeficiency disorders such as AIDS, humoral immune defect, ciliary dysfunction
 etc., and the use of immunosuppressive drugs (>30 mg prednisolone/day maintenance dose
 or equivalent for more than 4 weeks).

 -  Recent or unresolved lung malignancy.

 -  Other disease likely to require antibiotic therapy, such as recurrent sinusitis or
 urinary tract infection.

 -  Significant gastrointestinal or other conditions that may affect study drug
 absorption.

 -  Class III or IV congestive heart failure or stroke.

 -  Newly diagnosed pulmonary embolism