Comparison of a Serum PRO-CT Guided Treatment and the Recommended Antibiotic Treatment for COPD
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Study type: Observational

Summary: 
      Exacerbations of chronic obstructive pulmonary disease (COPD) are the first cause of
      admission to Pulmonary Department in Italy and worldwide. Guidelines recommend treating most
      patients hospitalized for exacerbations of COPD with antibiotics, even if the role of
      bacterial infection is often uncertain and the effect of antibiotics poor. The recommendation
      to use antibiotics is guided by clinical signs and symptoms that have an insufficient
      diagnostic accuracy, whereas serum biomarkers as procalcitonin (PRO-CT) may guide the
      selection of COPD patients who need antibiotic treatment. The main aim of the study is to
      investigate whether antibiotics can be safely stopped after 3 days or continued for 10 days
      according to a PRO-CT-guided algorithm in patients hospitalized for exacerbations of COPD for
      whom guidelines recommend 3-10 days antibiotic treatment based on presence of increased
      dyspnoea, sputum and purulence. The study is designed to assess the non inferiority of the
      PRO-CT guided plan as compared to the standard guideline recommended plan. The PRO-CT guided
      withholding of antibiotics is viewed as an experimental intervention associated with less
      antibiotic-associated complications, eg antibiotic resistance and drug-related side-effect
      and lower costs. The proposed study is a prospective, randomised controlled, single-blinded
      intervention trial comparing the standard with a PRO-CT guided antibiotic treatment plan.
      Patients will be recruited from the Pulmonary Department of 18 University or City Hospitals
      in Italy, starting October 2006 and continuing until December 2010. Results expected by end
      of 2011. The 100 patients randomised to the standard non PRO-CT guided antibiotic treatment
      plan will continue antibiotics for 10 days, whereas the 100 patients randomised to the PRO-CT
      guided antibiotic treatment plan will continue for 10 days or stop antibiotics on day 3
      depending on PRO-CT levels measured at admission, day 1 and day 2. Serum PRO-CT will be
      measured in a central laboratory. Patients will be examined at admission, discharge, 10 days,
      1, 3 and 6 months. A telephone interview will be obtained at 2, 4 and 5 months. The primary
      outcome of the study will be the rate of exacerbations. Secondary outcomes will be hospital
      readmission, admission to ICU, change in FEV1, duration of hospitalization, and death. The
      sample size was estimated according to the primary outcome of the study.
    

Detailed description: 
      Patients will be recruited from the Pulmonary Department of 18 University or City Hospitals
      in Italy, starting October 2006 and continuing until December 2010. The 100 patients
      randomised to the standard non PRO-CT guided antibiotic treatment plan will continue
      antibiotics for 10 days, whereas the 100 patients randomised to the PRO-CT-guided antibiotic
      treatment plan will continue for 10 days or stop antibiotics on day 3 depending on PRO-CT
      levels measured at admission, day 1 and day 2. Serum PRO-CT will be measured in a central
      laboratory. Patients will be examined at admission (visit 1), discharge and/or at 10 days
      (visit 4), 1 (visit 5), 3 (visit 6) and 6 months (visit 7). A telephone interview will be
      obtained at 2, 4 and 5 months. The primary outcome of the study will be the rate of
      exacerbations. Secondary outcomes will be hospital readmission, admission to ICU, change in
      FEV1, duration of hospitalization, and death. The sample size was estimated according to the
      primary outcome of the study.
    

Intervention name(s): PRO-CT values
Intervention type(s): Other
Intervention description(s): continue antibiotics for 10 days if a single PRO-CT value is 0.25 mcg/L or greater, that will be judged suggestive of bacterial infection
continue antibiotics from day 3 to day 10 if one or more PRO-CT values are 0.1 to 0.25 mcg/L, indicative of possible bacterial infection, PLUS acute respiratory failure or clinical instability
stop antibiotics on day 3, if one or more PRO-CT values are between 0.1 to 0.25 mcg/L, indicative of possible bacterial infection, BUT the patient has not acute respiratory failure or clinical instability
stop antibiotics if all the PRO-CT values are < 0.1 mcg/L or if there is a consistent trend to normalization of PRO-CT with the last value < 0.1 mcg/L, that will be judged suggestive of absence of bacterial infection.
Other intervention name(s): Amoxicilline + Clavulanate OR Quinolones
Intervention MeSH terms: Amoxicillin; Clavulanic Acid; Amoxicillin-Potassium Clavulanate Combination
Sampling method: Non-Probability Sample
Study population: 
        Patients with diagnosis of COPD according to GOLD guidelines
      
Biospecimen description: 
      Blood samples and sputum will be collected from COPD patients in order to measure serum
      PRO-CT levels and inflammatory markers (cells and mediators), respectively.
    
Keywords: COPD; PRO-CT; antibiotics