Antibiotic treatment of severe exacerbations of chronic obstructive pulmonary disease with procalcitonin

A randomized noninferiority trial

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

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

journal.pone.0118241 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. Methods and Findings 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).

Original languageEnglish
Article numbere0118241
JournalPLoS One
Volume10
Issue number3
DOIs
Publication statusPublished - Mar 11 2015

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Pulmonary diseases
Calcitonin
respiratory tract diseases
Chronic Obstructive Pulmonary Disease
antibiotics
Anti-Bacterial Agents
Therapeutics
confidence interval
Confidence Intervals
duration
bacterial infections
Biomarkers
Serum
Bacterial Infections
clinical trials
biomarkers
Italy
Clinical Trials

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Antibiotic treatment of severe exacerbations of chronic obstructive pulmonary disease with procalcitonin : A randomized noninferiority trial. / Verduri, Alessia; Luppi, Fabrizio; D'Amico, Roberto; Balduzzi, Sara; Vicini, Roberto; Liverani, Anna; Ruggieri, Valentina; Plebani, Mario; Barbaro, Maria Pia Foschino; Spanevello, Antonio; Canonica, Giorgio Walter; Papi, Alberto; Fabbri, Leonardo Michele; Beghè, Bianca.

In: PLoS One, Vol. 10, No. 3, e0118241, 11.03.2015.

Research output: Contribution to journalArticle

Verduri, A, Luppi, F, D'Amico, R, Balduzzi, S, Vicini, R, Liverani, A, Ruggieri, V, Plebani, M, Barbaro, MPF, Spanevello, A, Canonica, GW, Papi, A, Fabbri, LM & Beghè, B 2015, 'Antibiotic treatment of severe exacerbations of chronic obstructive pulmonary disease with procalcitonin: A randomized noninferiority trial', PLoS One, vol. 10, no. 3, e0118241. https://doi.org/10.1371/journal.pone.0118241
Verduri, Alessia ; Luppi, Fabrizio ; D'Amico, Roberto ; Balduzzi, Sara ; Vicini, Roberto ; Liverani, Anna ; Ruggieri, Valentina ; Plebani, Mario ; Barbaro, Maria Pia Foschino ; Spanevello, Antonio ; Canonica, Giorgio Walter ; Papi, Alberto ; Fabbri, Leonardo Michele ; Beghè, Bianca. / Antibiotic treatment of severe exacerbations of chronic obstructive pulmonary disease with procalcitonin : A randomized noninferiority trial. In: PLoS One. 2015 ; Vol. 10, No. 3.
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abstract = "journal.pone.0118241 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. Methods and Findings 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).",
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AU - Balduzzi, Sara

AU - Vicini, Roberto

AU - Liverani, Anna

AU - Ruggieri, Valentina

AU - Plebani, Mario

AU - Barbaro, Maria Pia Foschino

AU - Spanevello, Antonio

AU - Canonica, Giorgio Walter

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