A multi-center randomized, controlled, open-label trial evaluating the effects of eosinophil-guided corticosteroid-sparing therapy in hospitalised patients with COPD exacerbations - The CORTICO steroid reduction in COPD (CORTICO-COP) study protocol

Pradeesh Sivapalan, Mia Moberg, Josefin Eklöf, Julie Janner, Jørgen Vestbo, Rasmus Rude Laub, Andrea Browatzki, Karin Armbruster, Jon Torgny Wilcke, Niels Seersholm, Ulla Møller Weinreich, Ingrid Louise Titlestad, Helle Frost Andreassen, Charlotte Suppli Ulrik, Uffe Bødtger, Thyge Lynghøj Nielsen, Ejvind Frausing Hansen, Jens Ulrik Stæhr Jensen, Pradeesh Sivapalan, Mia Moberg, Josefin Eklöf, Julie Janner, Jørgen Vestbo, Rasmus Rude Laub, Andrea Browatzki, Karin Armbruster, Jon Torgny Wilcke, Niels Seersholm, Ulla Møller Weinreich, Ingrid Louise Titlestad, Helle Frost Andreassen, Charlotte Suppli Ulrik, Uffe Bødtger, Thyge Lynghøj Nielsen, Ejvind Frausing Hansen, Jens Ulrik Stæhr Jensen

Abstract

Background: The most commonly applied treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is a 5-day course of high-dose systemic corticosteroids. However, this treatment has not been shown to reduce mortality and can potentially have serious side effects. Recent research has shown that, presumably, only a subgroup of COPD patients identifieable by blood eosinophil count benefit from a rescue course of prednisolone. By applying a biomarker-guided strategy, the aim of this study is to determine whether it is possible to reduce the use of systemic corticosteroids in AECOPD without influencing the outcome.

Methods: This is an ongoing prospective multicenter randomized controlled open label trial comprising 320 patients with AECOPD recruited from four hospitals in Denmark. The patients are randomized 1:1 to either standard care or eosinophil-guided corticosteroid-sparing therapy where prednisolone is not administered if the daily blood sampling reveals an eosinophil level below 0.3 × 109 cells/L. The primary endpoint is length of hospital stay within 14 days after recruitment. The secondary endpoints are treatment failure, 30-day mortality rate, COPD related re-admission rate, change in FEV1, and a number of adverse effect measures obtained within 3 months after the index hospitalisation date related to corticosteroid usage.

Discussion: This will be a very large RCT providing knowledge about the effectiveness of individualized biomarker-guided corticosteroid therapy in hospitalised patients with AECOPD.

Trial registration: Clinicaltrials.gov, NCT02857842 , 02-august-2016. Clinicaltrialregister.eu: Classification Code: 10,010,953, 02-marts-2016.

Keywords: Aecopd; Biomarker; Copd; Eosinophil-guided corticosteroid-sparing therapy; Exacerbations; Gcp; Length of hospital stay; Randomized controlled trial; Systemic corticosteroids.

Conflict of interest statement

Ethics approval and consent to participate

The study will be carried out to include the protection of human subjects according to the 2008 Declaration of Helsinki and in accordance with Good Clinical Practice Guidelines. Patients will be informed about the study on admission day 1 and included if accepting to participate. A completed patient informed consent form is required from all patients participating in the study and must be signed by the patient and the informing physician. The study has been approved by the Ethics Committees of all participating sides (H-15012207) and the Danish Medicines Agency (EudraCT no: 201,500,344,126) and the Danish Data Protection Agency (HGH-2015-038 and I-Suite number 04014).

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flowchart of patients through the study

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