title: Antibiotic treatment of severe exacerbations of chronic obstructive pulmonary disease with procalcitonin: a randomized noninferiority trial.
abstract: BACKGROUND
  The duration of antibiotic treatment of exacerbations of COPD (ECOPD) is controversial. Serum procalcitonin (PCT) is a biomarker of bacterial infection used to identify the cause of ECOPD.
  
  
  RESULTS
  We investigated whether a PCT-guided plan would allow a shorter duration of antibiotic treatment in patients with severe ECOPD. For this multicenter, randomized, non-inferiority trial, we enrolled 184 patients hospitalized with ECOPD from 18 hospitals in Italy. Patients were assigned to receive antibiotics for 10 days (standard group) or for either 3 or 10 days (PCT group). The primary outcome was the rate of ECOPD at 6 months. Having planned to recruit 400 patients, we randomized only 183: 93 in the PCT group and 90 in the standard group. Thus, the completed study was underpowered. The ECOPD rate at 6 months between PCT-guided and standard antibiotic treatment was not significant (% difference, 4.04; 90% confidence interval [CI], -7.23 to 15.31), but the CI included the non-inferiority margin of 15. In the PCT-guided group, about 50% of patients were treated for 3 days, and there was no difference in primary or secondary outcomes compared to patients treated for 10 days.
  
  
  CONCLUSIONS
  Although the primary and secondary clinical outcomes were no different for patients treated for 3 or 10 days in the PCT group, the conclusion that antibiotics can be safely stopped after 3 days in patients with low serum PCT cannot be substantiated statistically. Thus, the results of this study are inconclusive regarding the noninferiority of the PCT-guided plan compared to the standard antibiotic treatment. The study was funded by Agenzia Italiana del Farmaco (AIFA-FARM58J2XH). Clinical trial registered with www.clinicaltrials.gov (NCT01125098).
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01125098.
authors.affiliation: Department of Oncology, Haematology and Respiratory Diseases, University of Modena & Reggio Emilia, Modena, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Verduri
authors.affiliation: Department of Oncology, Haematology and Respiratory Diseases, University of Modena & Reggio Emilia, Modena, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Luppi
authors.affiliation: Statistics Unit, Department of Diagnostic and Clinical Medicine and Public Health, University of Modena & Reggio Emilia, Modena, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: D'Amico
authors.affiliation: Statistics Unit, Department of Diagnostic and Clinical Medicine and Public Health, University of Modena & Reggio Emilia, Modena, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Balduzzi
authors.affiliation: Statistics Unit, Department of Diagnostic and Clinical Medicine and Public Health, University of Modena & Reggio Emilia, Modena, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Vicini
authors.affiliation: Department of Laboratory Medicine, University of Padova, Padova, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Liverani
authors.affiliation: Department of Oncology, Haematology and Respiratory Diseases, University of Modena & Reggio Emilia, Modena, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Ruggieri
authors.affiliation: Department of Laboratory Medicine, University of Padova, Padova, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.affiliation: Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
authors.forename: Maria Pia Foschino
authors.initials: MP
authors.lastname: Barbaro
authors.affiliation: Department of Clinical and Experimental Medicine, Division of Pulmonary Rehabilitation, Fondazione S. Maugeri (Tradate), University of Insubria, Varese, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Spanevello
authors.affiliation: Department of Respiratory & Allergic Diseases, University of Genova, Genova, Italy.
authors.forename: Giorgio Walter
authors.initials: GW
authors.lastname: Canonica
authors.affiliation: Department of Respiratory Diseases, University of Ferrara, Ferrara, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Papi
authors.affiliation: Department of Oncology, Haematology and Respiratory Diseases, University of Modena & Reggio Emilia, Modena, Italy.
authors.forename: Leonardo Michele
authors.initials: LM
authors.lastname: Fabbri
authors.affiliation: Department of Oncology, Haematology and Respiratory Diseases, University of Modena & Reggio Emilia, Modena, Italy.
authors.forename: Bianca
authors.initials: B
authors.lastname: Beghè
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000382:microbiology; D012141:Respiratory Tract Infections / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; C000606589:CALCA protein, human; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide