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.

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).

Trial Registration

ClinicalTrials.gov NCT01125098

Contributors

Natalie Walker: Role: Academic Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 11 March 2015

Publication date Collection: 2015

Volume: 10

Issue: 3

Affiliations

[1 ]Department of Oncology, Haematology and Respiratory Diseases, University of Modena & Reggio Emilia, Modena, Italy

[2 ]Statistics Unit, Department of Diagnostic and Clinical Medicine and Public Health, University of Modena & Reggio Emilia, Modena, Italy

[3 ]Department of Laboratory Medicine, University of Padova, Padova, Italy

[4 ]Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy

[5 ]Department of Clinical and Experimental Medicine, Division of Pulmonary Rehabilitation, Fondazione S. Maugeri (Tradate), University of Insubria, Varese, Italy

[6 ]Department of Respiratory & Allergic Diseases, University of Genova, Genova, Italy

[7 ]Department of Respiratory Diseases, University of Ferrara, Ferrara, Italy

The National Institute for Health Innovation, NEW ZEALAND

Author notes

Competing Interests: LMF received payment for consultancy from: Almirall, Boehringer LMF received payment for consultancy from: Almirall, Boehringer Ingelheim, Chiesi Farmaceutici, Euromediform, GlaxoSmithKline, Merck Sharp & Dhome, Mundipharma International, Novartis, Takeda, Pearl Therapeutics, Sterna, Peer Voice Europe, OM Pharma, TEVA; payment for lectures, advisory boards or travel expenses reimbursements from: AstraZeneca, Dey Pharma, Grünenthal GmbH, Mundipharma International, Novartis, Roche, Genetech Inc. AS declares he received personal benefits or personal travel grants or expenses for conferences from Boehringer, Novartis, Astrazeneca, Guidotti, Malesci, Almirall, Gsk, Mundipharma, Pfizer. AP gave presentations at symposia sponsored by, received research grants from, or served on scientific advisory boards of Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Dompè, GlaxoSmithKline, Guidotti, Menarini, MSD, Mundipharma, Novartis, Pfizer, Takeda, TEVA, Zambon. SB, VR, RV, MPFB, GWC, MP, FL, BB, AV, AL, RDA declare they have no conflicts. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Conceived and designed the experiments: AV FL RDA AP LMF BB. Performed the experiments: AL MP. Analyzed the data: RDA RV SB. Contributed reagents/materials/analysis tools: RV VR. Wrote the paper: AV FL RDA AP LMF BB.

¶ Membership of the FARM58J2XH Study Group is provided in the Acknowledgments.

* E-mail: leonardo.fabbri@ 123456unimore.it

Article

Publisher ID: PONE-D-14-29964

DOI: 10.1371/journal.pone.0118241

PMC ID: 4356612

PubMed ID: 25760346

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Page count

Figures: 3, Tables: 5, Pages: 16

Product

Funding

This research was supported by Agenzia Italiana del Farmaco (AIFA, Roma, Italy) (AIFA-FARM58J2XH); Consorzio Ferrara Ricerche (CFR, Ferrara, Italy); and Fondazione Chiesi, Parma, Italy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Categories

Subject: Research Article

Custom metadata

Data Availability All relevant data are within the paper and its Supporting Information files. The protocol is available at the following website: http://servertrial.unimore.it/proct/.