The primary objective of this study is to compare treatment failure rates between a group of eosinophilic (eosinophilia \> 2% on day 1 of hospitalization) patients hospitalised for a COPD exacerbation treated via corticotherapy versus a similar group treated via placebo. Secondarily, treatment failure rates will also be compared between a group of non-eosinophilic patients hospitalised for a COPD exacerbation treated via corticotherapy versus a similar group treated via placebo. Study arms will also be compared for additional aspects of efficacy and safety: * speed of recovery during the initial hospitalization; * corticosteroid side effects / induced comorbidities; * changes in symptoms and episodes of exacerbation; * pulmonary function, oxygen use and ventilation; * patient trajectories and resource use (e.g. survival, consults, episodes of hospitalization, medications); * drug consumption (especially as relates to COPD management, exacerbations and induced comorbidities); * health status, quality of life, activity/disability; * patient safety / adverse events in general. Eosinophilia thresholds optimizing the prediction of corticosteroid response and COPD outcomes will be re-evaluated. The relationships between corticosteroid response and key biomarkers (e.g. infectious groups) will be thoroughly explored, including within eosinophil strata. Potential gender subgroups differences will also be evaluated. Finally, in prevision of further exploratory studies, a biological collection and an imaging library will be created in association with this protocol. The biological collection will be used to explore the genetic basis and physiology linked with treatment response, gender and patient trajectories. The image library will be used as a platform for the exploration of new imaging markers developed, for example, via machine learning and affiliated techniques.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
600
Patients randomized to this arm will receive 40 mg prednisone per os per day for 5 days. Other aspects of standard, recommended care (e.g. antibiotherapy) are respected.
Patients randomized to this arm will receive an appropriate placebo per os for 5 days. Other aspects of standard, recommended care (e.g. antibiotherapy) are respected.
CHU Amiens
Amiens, France
NOT_YET_RECRUITINGCHU Brest - Hôpital Caval Blanche
Brest, France
RECRUITINGClinique du Parc
Castelnau-le-Lez, France
NOT_YET_RECRUITINGCentre hospitalier intercommunal de Créteil
Créteil, France
WITHDRAWNCH Libourne
Libourne, France
NOT_YET_RECRUITINGCHRU Lille
Lille, France
WITHDRAWNHospice Civils de Lyon
Lyon, France
RECRUITINGAPHM - Hôpital Nord
Marseille, France
RECRUITINGCHU Montpellier
Montpellier, France
RECRUITINGCHU Nancy
Nancy, France
RECRUITING...and 12 more locations
Treatment failure
Treatment failure for the primary outcome is defined according to Niewoehner et al. (1999) as death from any cause or need for intubation and mechanical ventilation, readmission due to COPD, or intensification of pharmacologic therapy (defined as the prescription of open-label systemic glucocorticoids, high-dose inhaled glucocorticoids (more than eight puffs per day of triamcinolone acetonide or its equivalent), theophylline, or any combination of these three therapies) at three months. In addition, an investigator meeting determined additional components of treatment failure that should be added to Niewoehner's definition in order to bring it up-to-date : * Initiation of non-invasive ventilation for \>24h after first treatment administration * Transfer to intensive care or indication for a transfer to intensive care. Incident limitations-of-care that can affect treatment failure should also be carefully noted.
Time frame: 3 months
The speed of initial recovery: Time elapsed before showing signs of improvement
Time frame: During initial hospitalization (expected maximum of 28 days)
The speed of initial recovery: Time elapsed in acidosis/hypercapnia
Time frame: During initial hospitalization (expected maximum of 28 days)
The speed of initial recovery: Time elapsed before meeting pre-defined discharge criteria
Time elapsed before meeting pre-defined discharge criteria (acidosis has normalized, symptoms have returned to manageable levels, the patient is capable of performing minimal daily activities).
Time frame: During initial hospitalization (expected maximum of 28 days)
Presence /absence of comorbidities or steroid side effects: glycemia
Time frame: During initial hospitalization (expected maximum of 28 days)
Presence /absence of comorbidities or steroid side effects: glycemia
Time frame: 1 month
Presence /absence of comorbidities or steroid side effects: glycemia
Time frame: 3 months
The occurrence of new or worsened diabetes/hyperglycemia
Time frame: Throughout the study (3 months)
Body mass index
Time frame: Baseline (day 0)
Body mass index
Time frame: At hospital discharge (expected maximum of 28 days)
Body mass index
Time frame: 1 month
Body mass index
Time frame: 3 month
Hospital anxiety and depression scale (HAD)
The HAD results in a score ranging from 0 (low anxiety or depression) to 21 (strong anxiety or depression).
Time frame: baseline (day 0)
Hospital anxiety and depression scale (HAD)
The HAD results in a score ranging from 0 (low anxiety or depression) to 21 (strong anxiety or depression).
Time frame: 3 months
The occurrence of any other potentially corticosteroid-induced comorbidities throughout the study
Time frame: Throughout the study; 3 months
Episodes of pneumonia
Beginning and end dates of episodes.
Time frame: Throughout the study; 3 months
Episodes of infection
Beginning and end dates of episodes.
Time frame: Throughout the study; 3 months
Episodes of mild exacerbation.
Episodes of exacerbation will be recorded (date of start/finish for each episode) throughout the study. Exacerbation severity is determined (GOLD 2018) as follows: * mild: treated with short acting bronchodilators (SABDs) only, * moderate: treated with SABDs plus antibiotics and/or oral corticosteroids, * severe: patient required hospitalization or visits the emergency room.
Time frame: Throughout the study; 3 months
Episodes of moderate exacerbation.
Episodes of exacerbation will be recorded (date of start/finish for each episode) throughout the study. Exacerbation severity is determined (GOLD 2018) as follows: * mild: treated with short acting bronchodilators (SABDs) only, * moderate: treated with SABDs plus antibiotics and/or oral corticosteroids, * severe: patient required hospitalization or visits the emergency room.
Time frame: Throughout the study; 3 months
Episodes of severe exacerbation.
Episodes of exacerbation will be recorded (date of start/finish for each episode) throughout the study. Exacerbation severity is determined (GOLD 2018) as follows: * mild: treated with short acting bronchodilators (SABDs) only, * moderate: treated with SABDs plus antibiotics and/or oral corticosteroids, * severe: patient required hospitalization or visits the emergency room.
Time frame: Throughout the study; 3 months
Forced expiratory volume in 1 second (litres)
Time frame: At hospital discharge (expected maximum of 28 days)
Forced expiratory volume in 1 second (litres)
Time frame: 3 months
Forced expiratory volume in 1 second (% predicted)
Time frame: At hospital discharge (expected maximum of 28 days)
Forced expiratory volume in 1 second (% predicted)
Time frame: 3 months
Forced vital capacity (litres)
Time frame: At hospital discharge (expected maximum of 28 days)
Forced vital capacity (litres)
Time frame: 3 months
Forced vital capacity (% predicted)
Time frame: At hospital discharge (expected maximum of 28 days)
Forced vital capacity (% predicted)
Time frame: 3 months
Residual volume (litres)
Time frame: At hospital discharge (expected maximum of 28 days)
Residual volume (litres)
Time frame: 3 months
Residual volume (% predicted)
Time frame: At hospital discharge (expected maximum of 28 days)
Residual volume (% predicted)
Time frame: 3 months
Total lung capacity (litres)
Time frame: At hospital discharge (expected maximum of 28 days)
Total lung capacity (litres)
Time frame: 3 months
Total lung capacity (% predicted)
Time frame: At hospital discharge (expected maximum of 28 days)
Total lung capacity (% predicted)
Time frame: 3 months
Oxygen needs (litres/min) during initial hospitalisation
Time frame: At hospital discharge (expected maximum of 28 days)
Mode of pre-hospitalization living arrangements
At home, rehabilitation centre, assisted living centre, or other
Time frame: Baseline (day 0)
Hospital discharge modality
At home, rehabilitation centre, assisted living centre, or other
Time frame: At hospital discharge (expected maximum of 28 days)
Episodes of hospitalization
Episodes of hospitalization, distinguishing emergency department, intensive care, intermediate care and ward stays, will be recorded throughout the study .
Time frame: Throughout the study; 3 months
Episodes of emergency department use
Time frame: Throughout the study; 3 months
Episodes of intensive care
Time frame: Throughout the study; 3 months
Consults
The number of consults and rehabilitation/therapy sessions in relation to COPD/respiratory symptoms (or not) will be tracked.
Time frame: Throughout the study; 3 months
The cumulative days alive and event-free
The cumulative days alive and event-free (free from hospitalization, exacerbation, ventilation, oxygen use, pneumonia or infection)
Time frame: Throughout the study; 3 months
Mortality/survival
Time frame: Throughout the study; 3 months
Medications
Drug consumption episodes (including vaccines) will be recorded throughout the study and linked to COPD exacerbations, COPD maintenance therapy or corticosteroid-induced side effects as appropriate.
Time frame: Throughout the study; 3 months
VAS scale for coughing
Patient reported, separate visual analogue scales (VAS) for coughing, dyspnoea (at rest), sputum production, sleep perturbation and anxiety. VAS scales range from 0 (absence of symptoms) to 10 (strongest possible symptoms imaginable).
Time frame: Every morning during hospitalization (expected maximum of 28 days)
VAS scale for coughing
Patient reported, separate visual analogue scales (VAS) for coughing, dyspnoea (at rest), sputum production, sleep perturbation and anxiety. VAS scales range from 0 (absence of symptoms) to 10 (strongest possible symptoms imaginable).
Time frame: 1 month
VAS scale for coughing
Patient reported, separate visual analogue scales (VAS) for coughing, dyspnoea (at rest), sputum production, sleep perturbation and anxiety. VAS scales range from 0 (absence of symptoms) to 10 (strongest possible symptoms imaginable).
Time frame: 3 months
VAS scale for dyspnoea
Patient reported, separate visual analogue scales (VAS) for coughing, dyspnoea (at rest), sputum production, sleep perturbation and anxiety. VAS scales range from 0 (absence of symptoms) to 10 (strongest possible symptoms imaginable).
Time frame: Every morning during hospitalization (expected maximum of 28 days)
VAS scale for dyspnoea
Patient reported, separate visual analogue scales (VAS) for coughing, dyspnoea (at rest), sputum production, sleep perturbation and anxiety. VAS scales range from 0 (absence of symptoms) to 10 (strongest possible symptoms imaginable).
Time frame: 1 month
VAS scale for dyspnoea
Patient reported, separate visual analogue scales (VAS) for coughing, dyspnoea (at rest), sputum production, sleep perturbation and anxiety. VAS scales range from 0 (absence of symptoms) to 10 (strongest possible symptoms imaginable).
Time frame: 3 months
VAS scale for sputum production
Patient reported, separate visual analogue scales (VAS) for coughing, dyspnoea (at rest), sputum production, sleep perturbation and anxiety. VAS scales range from 0 (absence of symptoms) to 10 (strongest possible symptoms imaginable).
Time frame: Every morning during hospitalization (expected maximum of 28 days)
VAS scale for sputum production
Patient reported, separate visual analogue scales (VAS) for coughing, dyspnoea (at rest), sputum production, sleep perturbation and anxiety. VAS scales range from 0 (absence of symptoms) to 10 (strongest possible symptoms imaginable).
Time frame: 1 month
VAS scale for sputum production
Patient reported, separate visual analogue scales (VAS) for coughing, dyspnoea (at rest), sputum production, sleep perturbation and anxiety. VAS scales range from 0 (absence of symptoms) to 10 (strongest possible symptoms imaginable).
Time frame: 3 months
VAS scale for sleep perturbation
Patient reported, separate visual analogue scales (VAS) for coughing, dyspnoea (at rest), sputum production, sleep perturbation and anxiety. VAS scales range from 0 (absence of symptoms) to 10 (strongest possible symptoms imaginable).
Time frame: Every morning during hospitalization (expected maximum of 28 days)
VAS scale for sleep perturbation
Patient reported, separate visual analogue scales (VAS) for coughing, dyspnoea (at rest), sputum production, sleep perturbation and anxiety. VAS scales range from 0 (absence of symptoms) to 10 (strongest possible symptoms imaginable).
Time frame: 1 month
VAS scale for sleep perturbation
Patient reported, separate visual analogue scales (VAS) for coughing, dyspnoea (at rest), sputum production, sleep perturbation and anxiety. VAS scales range from 0 (absence of symptoms) to 10 (strongest possible symptoms imaginable).
Time frame: 3 months
VAS scale for anxiety
Patient reported, separate visual analogue scales (VAS) for coughing, dyspnoea (at rest), sputum production, sleep perturbation and anxiety. VAS scales range from 0 (absence of symptoms) to 10 (strongest possible symptoms imaginable).
Time frame: Every morning during hospitalization (expected maximum of 28 days)
VAS scale for anxiety
Patient reported, separate visual analogue scales (VAS) for coughing, dyspnoea (at rest), sputum production, sleep perturbation and anxiety. VAS scales range from 0 (absence of symptoms) to 10 (strongest possible symptoms imaginable).
Time frame: 1 month
VAS scale for anxiety
Patient reported, separate visual analogue scales (VAS) for coughing, dyspnoea (at rest), sputum production, sleep perturbation and anxiety. VAS scales range from 0 (absence of symptoms) to 10 (strongest possible symptoms imaginable).
Time frame: 3 months
The Breathlessness, Cough and Sputum Scale
Symptoms are evaluated on a 5-point Likert-type scale ranging from 0 to 4, with higher scores indicating more severe symptoms.
Time frame: Baseline (day 0)
The Breathlessness, Cough and Sputum Scale
Symptoms are evaluated on a 5-point Likert-type scale ranging from 0 to 4, with higher scores indicating more severe symptoms.
Time frame: On hospital discharge (expected maximum of 28 days)
The Breathlessness, Cough and Sputum Scale
Symptoms are evaluated on a 5-point Likert-type scale ranging from 0 to 4, with higher scores indicating more severe symptoms.
Time frame: 1 month
The Breathlessness, Cough and Sputum Scale
Symptoms are evaluated on a 5-point Likert-type scale ranging from 0 to 4, with higher scores indicating more severe symptoms.
Time frame: 3 months
The modified medical research council (mMRC) dyspnoea scale
Scores range from 0 (none) to 4 (very severe).
Time frame: Baseline (day 0)
The modified medical research council (mMRC) dyspnoea scale
Scores range from 0 (none) to 4 (very severe).
Time frame: 3 months
The COPD assessment test
Scores range from 0-40 with higher scores indicative of greater COPD impact on health status.
Time frame: Baseline (day 0)
The COPD assessment test
Scores range from 0-40 with higher scores indicative of greater COPD impact on health status.
Time frame: 1 month
The COPD assessment test
Scores range from 0-40 with higher scores indicative of greater COPD impact on health status.
Time frame: 3 months
The Euroqol (EQ-5D-5L) questionnaire
The descriptive system has five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each described by five levels of intensity ("no problems", "slight problems", "moderate problems", "severe problems" and "extreme problems or complete inability"). This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.
Time frame: Baseline (day 0)
The Euroqol (EQ-5D-5L) questionnaire
The descriptive system has five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each described by five levels of intensity ("no problems", "slight problems", "moderate problems", "severe problems" and "extreme problems or complete inability"). This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.
Time frame: 1 month
The Euroqol (EQ-5D-5L) questionnaire
The descriptive system has five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each described by five levels of intensity ("no problems", "slight problems", "moderate problems", "severe problems" and "extreme problems or complete inability"). This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.
Time frame: 3 months
The St George Respiratory Questionnaire
Scores range from 0 to 100, with higher scores indicating more limitations.
Time frame: 3 months
Six minute walking tests
Time frame: 1 month (optional)
Six minute walking tests
Time frame: 3 months
The DIRECT questionnaire
DIRECT: Disability related to Chronic Obstructive Pulmonary Disease (COPD) tool The DIRECT questionnaire provides a score ranging between 0 and 34, with higher values indicating higher levels of disability.
Time frame: 3 months
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