Journal Article

Antibiotic Treatment of Severe Exacerbations of Chronic Obstructive Pulmonary Disease with Procalcitonin: A Randomized Noninferiority Trial

Ruggieri, Valentina, Vicini, Roberto, Beghè, Bianca, Verduri, Alessia, Plebani, Mario, Papi, Alberto, Liverani, Anna, Spanevello, Antonio, Canonica, Giorgio Walter, Barbaro, Maria Pia Foschino, Balduzzi, Sara, Luppi, Fabrizio, Fabbri, Leonardo Michele, D’Amico, Roberto

2015

Overview

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. 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. 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). ClinicalTrials.gov NCT01125098.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aged / Air pollution / Anti-Bacterial Agents - administration & dosage / Anti-Bacterial Agents - therapeutic use / Antibiotics / Asthma / Bacteria / Bacterial diseases / Bacterial infections / Bacterial Infections - drug therapy / Biomarkers / Biomarkers - blood / Calcitonin - blood / Calcitonin Gene-Related Peptide / Chronic obstructive lung disease / Chronic obstructive pulmonary disease / Clinical medicine / Clinical trials / Confidence intervals / Diagnosis / Dosage and administration / Drug Administration Schedule / Drug Monitoring / Drug therapy / Dyspnea / Female / Health aspects / Hematology / Hospital admission and discharge / Hospitalization / Humans / Infections / Italy / Laboratories / Lung diseases / Male / Management / Medicine / Mortality / Obstructive lung disease / Oncology / Outdoor air quality / Patient outcomes / Patients / Pneumonia / Procalcitonin / Prospective Studies / Protein Precursors - blood / Public health / Pulmonary Disease, Chronic Obstructive - drug therapy / Pulmonary Disease, Chronic Obstructive - microbiology / Randomization / Respiratory diseases / Respiratory Tract Infections - drug therapy / Studies / Treatment Outcome / Viral infections