Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Eosinophil-guided corticosteroid therapy in patients admitted to hospital with COPD exacerbation (CORTICO-COP): a multicentre, randomised, controlled, open-label, non-inferiority trial

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

APA

CBE

MLA

Vancouver

Author

Bibtex

@article{85386b15657a45349399b660201d7668,
title = "Eosinophil-guided corticosteroid therapy in patients admitted to hospital with COPD exacerbation (CORTICO-COP): a multicentre, randomised, controlled, open-label, non-inferiority trial",
abstract = "Background: Treatment with systemic corticosteroids in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) is associated with debilitating adverse effects. Therefore, strategies to reduce systemic corticosteroid exposure are urgently required and might be offered by a personalised biomarker-guided approach to treatment. The aim of this study was to determine whether an algorithm based on blood eosinophil counts could safely reduce systemic corticosteroid exposure in patients admitted to hospital with acute exacerbations of COPD. Methods: We did a multicentre, randomised, controlled, open-label, non-inferiority trial at the respiratory departments of three different university-affiliated hospitals in Denmark. Eligible participants were patients included within 24h of admission to the participating sites, aged at least 40 years, with known airflow limitation (defined as a post-bronchodilator FEV 1/forced vital capacity [FVC] ratio ≤0·70) and a specialist-verified diagnosis of COPD, who were designated to start on systemic corticosteroids by the respiratory medicine physician on duty. We randomly assigned patients (1:1) to either eosinophil-guided therapy or standard therapy with systemic corticosteroids. Both investigators and patients were aware of the group assignment. All patients received 80 mg of intravenous methylprednisolone on the first day. The eosinophil-guided group were from the second day given 37·5 mg of prednisolone oral tablet daily (for a maximum of up to 4 days) on days when their blood eosinophil count was at least 0·3 × 10 9 cells per L. On days when the eosinophil count was lower, prednisolone was not administered. If a patient was discharged during the treatment period, a treatment based on the last measured eosinophil count was prescribed for the remaining days within the 5-day period (last observation carried forward). The control group received 37·5 mg of prednisolone tablets daily from the second day for 4 days. The primary outcome was the number of days alive and out of hospital within 14 days after recruitment, assessed by intention to treat (ITT). Secondary outcomes included treatment failure at day 30 (ie, recurrence of acute exacerbation of COPD resulting in emergency room visits, admission to hospital, or need to intensify pharmacological treatment), number of deaths on day 30, and duration of treatment with systemic corticosteroids. The non-inferiority margin was 1·2 days (SD 3·8). This trial is registered at ClinicalTrials.gov, number NCT02857842, and was completed in January, 2019. Findings: Between Aug 3, 2016, and Sept 30, 2018, 159 patients in the eosinophil-guided group and 159 patients in the control group were included in the ITT analyses. There was no between-group difference for days alive and out of hospital within 14 days after recruitment: mean 8·9 days (95{\%} CI 8·3–9·6) in the eosinophil-guided group versus 9·3 days (8·7–9·9) in the control group (absolute difference –0·4, 95{\%} CI −1·3 to 0·5; p=0·34). Treatment failure at 30 days occurred in 42 (26{\%}) of 159 patients in the eosinophil-guided group and 41 (26{\%}) of 159 in the control group (difference 0·6{\%}, 95{\%} CI −9·0 to 10·3; p=0·90). At 30 days nine patients (6{\%}) of 159 in the eosinophil-guided group and six (4{\%}) of 159 in the control group had died (difference 1·9{\%}, 95{\%} CI −2·8 to 6·5; p=0·43). Median duration of systemic corticosteroid therapy was lower in the eosinophil-guided group: 2 days (IQR 1·0 to 3·0) compared with 5 days (5·0 to 5·0) in the control group, p<0·0001. Interpretation: Eosinophil-guided therapy was non-inferior compared with standard care for the number of days alive and out of hospital, and reduced the duration of systemic corticosteroid exposure, although we could not entirely exclude harm on some secondary outcome measures. Larger studies will help to determine the full safety profile of this strategy and its role in the management of COPD exacerbations. Funding: The Danish Regions Medical Fund and the Danish Council for Independent Research.",
author = "Pradeesh Sivapalan and Lapperre, {Therese S} and Julie Janner and Laub, {Rasmus R} and Mia Moberg and Bech, {Charlotte S} and Josefin Ekl{\"o}f and Holm, {Freja S} and Karin Armbruster and Praleene Sivapalan and Christiane Mosbech and Ali, {Aras K M} and Niels Seersholm and Wilcke, {Jon T} and Eva Br{\o}ndum and Sonne, {Tine P} and Finn R{\o}nholt and Andreassen, {Helle F} and Ulrik, {Charlotte S} and J{\o}rgen Vestbo and Jensen, {Jens-Ulrik S}",
note = "Copyright {\circledC} 2019 Elsevier Ltd. All rights reserved.",
year = "2019",
month = "8",
doi = "10.1016/S2213-2600(19)30176-6",
language = "English",
volume = "7",
pages = "699--709",
journal = "The Lancet Respiratory Medicine",
issn = "2213-2600",
publisher = "Elsevier",
number = "8",

}

RIS

TY - JOUR

T1 - Eosinophil-guided corticosteroid therapy in patients admitted to hospital with COPD exacerbation (CORTICO-COP)

T2 - a multicentre, randomised, controlled, open-label, non-inferiority trial

AU - Sivapalan, Pradeesh

AU - Lapperre, Therese S

AU - Janner, Julie

AU - Laub, Rasmus R

AU - Moberg, Mia

AU - Bech, Charlotte S

AU - Eklöf, Josefin

AU - Holm, Freja S

AU - Armbruster, Karin

AU - Sivapalan, Praleene

AU - Mosbech, Christiane

AU - Ali, Aras K M

AU - Seersholm, Niels

AU - Wilcke, Jon T

AU - Brøndum, Eva

AU - Sonne, Tine P

AU - Rønholt, Finn

AU - Andreassen, Helle F

AU - Ulrik, Charlotte S

AU - Vestbo, Jørgen

AU - Jensen, Jens-Ulrik S

N1 - Copyright © 2019 Elsevier Ltd. All rights reserved.

PY - 2019/8

Y1 - 2019/8

N2 - Background: Treatment with systemic corticosteroids in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) is associated with debilitating adverse effects. Therefore, strategies to reduce systemic corticosteroid exposure are urgently required and might be offered by a personalised biomarker-guided approach to treatment. The aim of this study was to determine whether an algorithm based on blood eosinophil counts could safely reduce systemic corticosteroid exposure in patients admitted to hospital with acute exacerbations of COPD. Methods: We did a multicentre, randomised, controlled, open-label, non-inferiority trial at the respiratory departments of three different university-affiliated hospitals in Denmark. Eligible participants were patients included within 24h of admission to the participating sites, aged at least 40 years, with known airflow limitation (defined as a post-bronchodilator FEV 1/forced vital capacity [FVC] ratio ≤0·70) and a specialist-verified diagnosis of COPD, who were designated to start on systemic corticosteroids by the respiratory medicine physician on duty. We randomly assigned patients (1:1) to either eosinophil-guided therapy or standard therapy with systemic corticosteroids. Both investigators and patients were aware of the group assignment. All patients received 80 mg of intravenous methylprednisolone on the first day. The eosinophil-guided group were from the second day given 37·5 mg of prednisolone oral tablet daily (for a maximum of up to 4 days) on days when their blood eosinophil count was at least 0·3 × 10 9 cells per L. On days when the eosinophil count was lower, prednisolone was not administered. If a patient was discharged during the treatment period, a treatment based on the last measured eosinophil count was prescribed for the remaining days within the 5-day period (last observation carried forward). The control group received 37·5 mg of prednisolone tablets daily from the second day for 4 days. The primary outcome was the number of days alive and out of hospital within 14 days after recruitment, assessed by intention to treat (ITT). Secondary outcomes included treatment failure at day 30 (ie, recurrence of acute exacerbation of COPD resulting in emergency room visits, admission to hospital, or need to intensify pharmacological treatment), number of deaths on day 30, and duration of treatment with systemic corticosteroids. The non-inferiority margin was 1·2 days (SD 3·8). This trial is registered at ClinicalTrials.gov, number NCT02857842, and was completed in January, 2019. Findings: Between Aug 3, 2016, and Sept 30, 2018, 159 patients in the eosinophil-guided group and 159 patients in the control group were included in the ITT analyses. There was no between-group difference for days alive and out of hospital within 14 days after recruitment: mean 8·9 days (95% CI 8·3–9·6) in the eosinophil-guided group versus 9·3 days (8·7–9·9) in the control group (absolute difference –0·4, 95% CI −1·3 to 0·5; p=0·34). Treatment failure at 30 days occurred in 42 (26%) of 159 patients in the eosinophil-guided group and 41 (26%) of 159 in the control group (difference 0·6%, 95% CI −9·0 to 10·3; p=0·90). At 30 days nine patients (6%) of 159 in the eosinophil-guided group and six (4%) of 159 in the control group had died (difference 1·9%, 95% CI −2·8 to 6·5; p=0·43). Median duration of systemic corticosteroid therapy was lower in the eosinophil-guided group: 2 days (IQR 1·0 to 3·0) compared with 5 days (5·0 to 5·0) in the control group, p<0·0001. Interpretation: Eosinophil-guided therapy was non-inferior compared with standard care for the number of days alive and out of hospital, and reduced the duration of systemic corticosteroid exposure, although we could not entirely exclude harm on some secondary outcome measures. Larger studies will help to determine the full safety profile of this strategy and its role in the management of COPD exacerbations. Funding: The Danish Regions Medical Fund and the Danish Council for Independent Research.

AB - Background: Treatment with systemic corticosteroids in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) is associated with debilitating adverse effects. Therefore, strategies to reduce systemic corticosteroid exposure are urgently required and might be offered by a personalised biomarker-guided approach to treatment. The aim of this study was to determine whether an algorithm based on blood eosinophil counts could safely reduce systemic corticosteroid exposure in patients admitted to hospital with acute exacerbations of COPD. Methods: We did a multicentre, randomised, controlled, open-label, non-inferiority trial at the respiratory departments of three different university-affiliated hospitals in Denmark. Eligible participants were patients included within 24h of admission to the participating sites, aged at least 40 years, with known airflow limitation (defined as a post-bronchodilator FEV 1/forced vital capacity [FVC] ratio ≤0·70) and a specialist-verified diagnosis of COPD, who were designated to start on systemic corticosteroids by the respiratory medicine physician on duty. We randomly assigned patients (1:1) to either eosinophil-guided therapy or standard therapy with systemic corticosteroids. Both investigators and patients were aware of the group assignment. All patients received 80 mg of intravenous methylprednisolone on the first day. The eosinophil-guided group were from the second day given 37·5 mg of prednisolone oral tablet daily (for a maximum of up to 4 days) on days when their blood eosinophil count was at least 0·3 × 10 9 cells per L. On days when the eosinophil count was lower, prednisolone was not administered. If a patient was discharged during the treatment period, a treatment based on the last measured eosinophil count was prescribed for the remaining days within the 5-day period (last observation carried forward). The control group received 37·5 mg of prednisolone tablets daily from the second day for 4 days. The primary outcome was the number of days alive and out of hospital within 14 days after recruitment, assessed by intention to treat (ITT). Secondary outcomes included treatment failure at day 30 (ie, recurrence of acute exacerbation of COPD resulting in emergency room visits, admission to hospital, or need to intensify pharmacological treatment), number of deaths on day 30, and duration of treatment with systemic corticosteroids. The non-inferiority margin was 1·2 days (SD 3·8). This trial is registered at ClinicalTrials.gov, number NCT02857842, and was completed in January, 2019. Findings: Between Aug 3, 2016, and Sept 30, 2018, 159 patients in the eosinophil-guided group and 159 patients in the control group were included in the ITT analyses. There was no between-group difference for days alive and out of hospital within 14 days after recruitment: mean 8·9 days (95% CI 8·3–9·6) in the eosinophil-guided group versus 9·3 days (8·7–9·9) in the control group (absolute difference –0·4, 95% CI −1·3 to 0·5; p=0·34). Treatment failure at 30 days occurred in 42 (26%) of 159 patients in the eosinophil-guided group and 41 (26%) of 159 in the control group (difference 0·6%, 95% CI −9·0 to 10·3; p=0·90). At 30 days nine patients (6%) of 159 in the eosinophil-guided group and six (4%) of 159 in the control group had died (difference 1·9%, 95% CI −2·8 to 6·5; p=0·43). Median duration of systemic corticosteroid therapy was lower in the eosinophil-guided group: 2 days (IQR 1·0 to 3·0) compared with 5 days (5·0 to 5·0) in the control group, p<0·0001. Interpretation: Eosinophil-guided therapy was non-inferior compared with standard care for the number of days alive and out of hospital, and reduced the duration of systemic corticosteroid exposure, although we could not entirely exclude harm on some secondary outcome measures. Larger studies will help to determine the full safety profile of this strategy and its role in the management of COPD exacerbations. Funding: The Danish Regions Medical Fund and the Danish Council for Independent Research.

UR - http://www.scopus.com/inward/record.url?scp=85069635232&partnerID=8YFLogxK

U2 - 10.1016/S2213-2600(19)30176-6

DO - 10.1016/S2213-2600(19)30176-6

M3 - Journal article

VL - 7

SP - 699

EP - 709

JO - The Lancet Respiratory Medicine

JF - The Lancet Respiratory Medicine

SN - 2213-2600

IS - 8

ER -

ID: 57326648