Clinical trial NCT02857842: Corticosteroid Reduction in COPD
Official title: The Effect of Reduced Corticosteroid Therapy in Patients With Acute Exacerbation of COPD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Lung Diseases, Obstructive
Blood Eosinophil Count
Glucocorticoids
COPD
Pulmonary Disease, Chronic Obstructive
Lead sponsor: Chronic Obstructive Pulmonary Disease Trial Network, Denmark
Sponsor class: OTHER
First posted: 2016-08-05
Enrollment: 318
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study explores whether patients hospitalized with chronic obstructive pulmonary disease (COPD) exacerbation may have fewer days with prednisolone and with the same treatment effect by controlling the treatment by daily measurements of eosinophils.

Detailed description: The most commonly used treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is a 5-day treatment with corticosteroids in moderate-high dose. Some patients receive repeated treatments, although it has been shown that corticosteroids only have temporary beneficial effects and no effect in relation to serious incidents or mortality. It has been found that the higher accumulated prednisolone dose disables patients due to serious side effects, including pneumonia, dysregulated diabetes, bone fracture in the context of osteoporosis, mental disorder and adrenal insufficiency etc. However, the extent of the side effects is unknown. Recent research has shown that it is presumably only a small subset of COPD patients who benefit from corticosteroid therapy. This group can be identified by the biomarker "blood-eosinophils" as already measured on most AECOPD patients during hospitalization.

This is a randomized, controlled, multi-center, non-Inferiority trial evaluating the effect of eosinophil guided corticosteroid therapy to patients with AECOPD. The aim of the study is to investigate whether the accumulated dose corticosteroid treatment during admissions for AECOPD can be reduced, including the presumed side effects, while (still) remaining the optimal treatment effect.

Eligibility criteria: Inclusion criteria:

* Patients hospitalized with AECOPD
* Age ≥ 40 years
* Spirometry-verified COPD (defined as FEV1 / FVC ≤ 70%)
* Chronic Obstructive Lung Disease (GOLD) class C or D
* Inclusion within 24 hours after admission

Exclusion criteria:

* Known with a diagnosis of asthma
* Life expectancy less than 30 days
* Serious exacerbation requiring invasive ventilation or admission to ICU
* Allergy to systemic corticosteroids
* Severe mental illness, which is not controlled by medication
* People who are detained under the act on the use of coercion in psychiatry
* Severe language problems or inability to provide written informed consent
* Pregnancy and lactation
* Systemic fungal infections

Primary outcomes:
measure: Days alive and out of hospital within 14 days after recruitment
timeFrame: 14 days from recruitment
Secondary outcomes:
measure: Treatment failure (Recurrence of AECOPD resulting in emergency room visits, hospitalization or need to intensify pharmacological treatment within 30 days)
timeFrame: 30 days
measure: Change in lung function (ΔFEV1) on day 3, after 1 month and 3 month
timeFrame: 90 days
measure: Mortality
timeFrame: 360 days
measure: Infection requiring antibiotic treatment within 180 days after the index of AECOPD
timeFrame: 180 days
measure: The period between index AECOPD and the next AECOPD exacerbation
timeFrame: 90 days
measure: Cumulative corticosteroid dose at 1 and 3 month follow-up
timeFrame: 90 days
measure: Hyperglycemia during admission
timeFrame: 14 days
measure: Changes in PTH and Vitamin D status between hospitalization and 3-month follow-up
timeFrame: 90 days
measure: Change in bone marker levels (Serum P1NP, Serum CTX)
timeFrame: 90 days
measure: Dyspepsia or ulcer complications (gastrointestinal bleeding)
timeFrame: 90 days
measure: New onset or worsening of diabetes mellitus
timeFrame: 30 days
measure: Increase in body mass index between hospitalization, at 30 days and 3-month follow-up
timeFrame: 90 days
measure: The impact of COPD (cough, sputum, dysnea, chest tightsenes etc) on health status (COPD Assessment Test) between hospitalization, at 30 days and 3-month follow-up
timeFrame: 90 days
measure: Changes in level of dyspnea using the Medical Research Council (MRC) Dyspnoea Scale between hospitalization, at 30 days and 3-month follow-up
timeFrame: 90 days
measure: Osteoporotic fractures
timeFrame: 360 days
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Bispebjerg University Hospital
city: Copenhagen
country: Denmark
facility: Hvidovre University Hospital
city: Copenhagen
country: Denmark
facility: North Zealand Hospital
city: Hellerup
country: Denmark
facility: Gentofte University Hospital
Study officials:
References:
citation: Sivapalan P, Jorgensen NR, Mathioudakis AG, Eklof J, Lapperre T, Ulrik CS, Andreassen HF, Armbruster K, Sivapalan P, Janner J, Godtfredsen N, Weinreich UM, Nielsen TL, Seersholm N, Wilcke T, Schuetz P, Klausen TW, Marsa K, Vestbo J, Jensen JU. Bone turnover biomarkers in COPD patients randomized to either a regular or shortened course of corticosteroids: a substudy of the randomized controlled CORTICO-COP trial. Respir Res. 2020 Oct 12;21(1):263. doi: 10.1186/s12931-020-01531-9.
citation: Sivapalan P, Lapperre TS, Janner J, Laub RR, Moberg M, Bech CS, Eklof J, Holm FS, Armbruster K, Sivapalan P, Mosbech C, Ali AKM, Seersholm N, Wilcke JT, Brondum E, Sonne TP, Ronholt F, Andreassen HF, Ulrik CS, Vestbo J, Jensen JS. Eosinophil-guided corticosteroid therapy in patients admitted to hospital with COPD exacerbation (CORTICO-COP): a multicentre, randomised, controlled, open-label, non-inferiority trial. Lancet Respir Med. 2019 Aug;7(8):699-709. doi: 10.1016/S2213-2600(19)30176-6. Epub 2019 May 20.
citation: Sivapalan P, Moberg M, Eklof J, Janner J, Vestbo J, Laub RR, Browatzki A, Armbruster K, Wilcke JT, Seersholm N, Weinreich UM, Titlestad IL, Andreassen HF, Ulrik CS, Bodtger U, Nielsen TL, Hansen EF, Jensen JUS. 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. BMC Pulm Med. 2017 Aug 15;17(1):114. doi: 10.1186/s12890-017-0458-7.