Corticosteroid Reduction in COPD (Cortico-cop)

• ClinicalTrials.gov Identifier: NCT02857842
• Recruitment Status: Completed
• First Posted: August 5, 2016
• Last Update Posted: February 8, 2019
• Sponsor: Chronic Obstructive Pulmonary Disease Trial Network, Denmark
• Information provided by (Responsible Party): Pradeesh Sivapalan, Chronic Obstructive Pulmonary Disease Trial Network, Denmark

Tracking Information

• First Submitted Date: August 2, 2016
• First Posted Date: August 5, 2016
• Last Update Posted Date: February 8, 2019
• Study Start Date: August 2016
• Actual Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 2, 2016): Days alive and out of hospital within 14 days after recruitment [ Time Frame: 14 days from recruitment ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 21, 2018)

• Treatment failure (Recurrence of AECOPD resulting in emergency room visits, hospitalization or need to intensify pharmacological treatment within 30 days) [ Time Frame: 30 days ]
• Change in lung function (ΔFEV1) on day 3, after 1 month and 3 month [ Time Frame: 90 days ]
• Mortality [ Time Frame: 360 days ]
• Infection requiring antibiotic treatment within 180 days after the index of AECOPD [ Time Frame: 180 days ]
• The period between index AECOPD and the next AECOPD exacerbation [ Time Frame: 90 days ]
  1. Readmission with AECOPD or death
  2. Time to readmission with AECOPD or death
• Cumulative corticosteroid dose at 1 and 3 month follow-up [ Time Frame: 90 days ]
  1. Proportions of patients using corticosteroids during hospitalization (day 1 to day 5) between treatment arms
  2. Mean total cumulative dose from recruitment to 3-month follow-up
• Hyperglycemia during admission [ Time Frame: 14 days ]
• Changes in PTH and Vitamin D status between hospitalization and 3-month follow-up [ Time Frame: 90 days ]
• Change in bone marker levels (Serum P1NP, Serum CTX) [ Time Frame: 90 days ]
• Dyspepsia or ulcer complications (gastrointestinal bleeding) [ Time Frame: 90 days ]
• New onset or worsening of diabetes mellitus [ Time Frame: 30 days ]
• Increase in body mass index between hospitalization, at 30 days and 3-month follow-up [ Time Frame: 90 days ]
• 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 [ Time Frame: 90 days ]
• Changes in level of dyspnea using the Medical Research Council (MRC) Dyspnoea Scale between hospitalization, at 30 days and 3-month follow-up [ Time Frame: 90 days ]
• Osteoporotic fractures [ Time Frame: 360 days ]

Original Secondary Outcome Measures (submitted: August 2, 2016)

• Treatment failure (Recurrence of COPD exacerbation resulting in emergency room visits, hospitalization or need to intensify pharmacological treatment within 30 days) [ Time Frame: 30 days ]
• Change in lung function (ΔFEV1) on day 3, after 1 month and 3 month [ Time Frame: 90 days ]
• Mortality [ Time Frame: 180 days ]
• Infection requiring antibiotic treatment within 180 days after the index COPD exacerbation [ Time Frame: 180 days ]
• The period between index COPD exacerbation and next COPD exacerbation [ Time Frame: 90 days ]
• Cumulative corticosteroid dose at 1 and 3 month follow-up [ Time Frame: 90 days ]
• Hyperglycemia during admission [ Time Frame: 14 days ]
• Adrenal insufficiency [ Time Frame: 30 days ]
• Change in bone marker levels (Serum P1NP, Serum CTX) [ Time Frame: 90 days ]
• Gastrointestinal bleeding [ Time Frame: 90 days ]
• Diabetes mellitus [ Time Frame: 30 days ]
• Increase in body mass index [ Time Frame: 90 days ]
• The impact of COPD (cough, sputum, dysnea, chest tighteness) on health status (COPD Assessment Test) [ Time Frame: 90 days ]
• MRC score [ Time Frame: 90 days ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Corticosteroid Reduction in COPD
• Official Title: The Effect of Reduced Corticosteroid Therapy in Patients With Acute Exacerbation of COPD
• 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.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Lung Diseases, Obstructive
• Blood Eosinophil Count
• Glucocorticoids
• COPD
• Pulmonary Disease, Chronic Obstructive

• Intervention: Drug: Prednisolone

Study Arms

• Experimental: Blood eosinophil guided prednisolone treatment
  Intravenous Solu-Medrol 80 mg, followed by prednisolone tablet 37.5 mg daily (maximum of 5 days in all) if the eosinophil count in the blood ≥ 0.3 x 10E9/L. Eosinophil count in the blood <0.3 x 10E9/L results in no treatment with prednisolone. If the patient is discharged during the treatment period, given treatment from the last measured eosinophil count the remaining days.
  Intervention: Drug: Prednisolone
• Active Comparator: Standard of care
  Intravenous Solu-Medrol 80 mg on the first day followed by 37.5 mg of prednisolone tablets (1 x 25 mg plus 1 x 12.5 mg) daily for 5 days
  Intervention: Drug: Prednisolone

Publications *

• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 2, 2016): 318
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: January 2019
• Actual Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark

Administrative Information

• NCT Number: NCT02857842
• Other Study ID Numbers: Protocol_CORTICO-COP_PSJUJ
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)

• Current Responsible Party: Pradeesh Sivapalan, Chronic Obstructive Pulmonary Disease Trial Network, Denmark
• Original Responsible Party: Same as current
• Current Study Sponsor: Chronic Obstructive Pulmonary Disease Trial Network, Denmark
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Chronic Obstructive Pulmonary Disease Trial Network, Denmark
• Verification Date: February 2019