Eosinophil-driven Corticotherapy for Patients Hospitalized for COPD Exacerbation
- Conditions
- COPD Exacerbation
- Interventions
- Drug: 5 days of placeboDrug: 5 days of systemic corticotherapy (prednisone)
- Registration Number
- NCT04234360
- Lead Sponsor
- University Hospital, Montpellier
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 600
- Adult patients admitted to a participating hospital (ward, ICU or emergency services) for an acute COPD exacerbation
- For patients with known COPD: COPD defined according to GOLD 2018 criteria: (1) Post-bronchodilator FEV1/FVC < 70% of predicted values; (2) > 10 pack years smoking history
- For incident COPD cases with no spirometric history: symptoms and exposure according to GOLD 2018 report will be considered for the diagnosis, but if the spirometric diagnosis is not confirmed during follow-up, then the patient will be excluded
- Signed consent has been obtained, or the appropriate emergency procedure (under French law) allows enrolment
- Subjects must be covered by public health insurance
- Patient available for 3 months of follow-up. Subjects must be able to attend all scheduled visits and to comply with all trial procedures.
- Subject unable to read or write; language barrier
- Subject who is in a dependency or employment with the sponsor or investigator
- Pregnancy or lactation
- Patients who are prisoners or under other forms of judicial protection
- Patients under any kind of guardianship
- The patient has already participated in the present protocol
- The patient is participating in another interventional study or has done so in the past 3 months
- The patient is in an exclusion period determined by a previous study
- The patient has been taking long-term systemic corticosteroids for longer than 1 month prior to inclusion
- The patient has already received > 1 mg/kg of systemic corticotherapy in the past 48h
- Intubated-ventilated patient
- Administration of oral experimental drug is impossible
- Cancer within the last 12 months
- Current diagnosis of Asthma
- T2-inflammation targeting biologics (Benralizumab, reslizumab, mepolizumab, dupilumab) treatment
- Admitted for any other reason including, but not limited to, pulmonary embolism, pneumothorax, heart failure
- Known allergy to corticosteroids
- Consideration of a potential negative drug interaction with corticosteroids (at the investigator's discretion)
- White blood cell formula already performed and distributed to implicated teams
- Directives for limitation-of-care ("LATA" in French) already established
- SARS-Cov2 positive test carry out during the COPD exacerbation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Eosinophil count > 2%; placebo 5 days of placebo Eosinophilic patients randomized to this arm will receive 5 days of placebo. Eosinophil count <= 2%; placebo 5 days of placebo Non-eosinophilic patients randomized to this arm will receive 5 days of placebo. Eosinophil count > 2%; corticotherapy 5 days of systemic corticotherapy (prednisone) Eosinophilic patients randomized to this arm will receive 5 days of corticotherapy. Eosinophil count <= 2%; corticotherapy 5 days of systemic corticotherapy (prednisone) Non-eosinophilic patients randomized to this arm will receive 5 days of corticotherapy.
- Primary Outcome Measures
Name Time Method Treatment failure 3 months 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.
- Secondary Outcome Measures
Name Time Method Body mass index 3 month The speed of initial recovery: Time elapsed before showing signs of improvement During initial hospitalization (expected maximum of 28 days) The speed of initial recovery: Time elapsed in acidosis/hypercapnia During initial hospitalization (expected maximum of 28 days) Presence /absence of comorbidities or steroid side effects: glycemia 3 months The occurrence of new or worsened diabetes/hyperglycemia Throughout the study (3 months) The occurrence of any other potentially corticosteroid-induced comorbidities throughout the study Throughout the study; 3 months Episodes of infection Throughout the study; 3 months Beginning and end dates of episodes.
Residual volume (litres) 3 months Residual volume (% predicted) 3 months Total lung capacity (litres) 3 months Total lung capacity (% predicted) 3 months Consults Throughout the study; 3 months The number of consults and rehabilitation/therapy sessions in relation to COPD/respiratory symptoms (or not) will be tracked.
The speed of initial recovery: Time elapsed before meeting pre-defined discharge criteria During initial hospitalization (expected maximum of 28 days) 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).
Hospital anxiety and depression scale (HAD) 3 months The HAD results in a score ranging from 0 (low anxiety or depression) to 21 (strong anxiety or depression).
Episodes of moderate exacerbation. Throughout the study; 3 months 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.Episodes of hospitalization Throughout the study; 3 months Episodes of hospitalization, distinguishing emergency department, intensive care, intermediate care and ward stays, will be recorded throughout the study .
The cumulative days alive and event-free Throughout the study; 3 months The cumulative days alive and event-free (free from hospitalization, exacerbation, ventilation, oxygen use, pneumonia or infection)
Medications Throughout the study; 3 months 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.
VAS scale for dyspnoea 3 months 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).The COPD assessment test 3 months Scores range from 0-40 with higher scores indicative of greater COPD impact on health status.
The DIRECT questionnaire 3 months 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.
Episodes of pneumonia Throughout the study; 3 months Beginning and end dates of episodes.
Episodes of mild exacerbation. Throughout the study; 3 months 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.Forced vital capacity (% predicted) 3 months Episodes of intensive care Throughout the study; 3 months VAS scale for coughing 3 months 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).VAS scale for anxiety 3 months 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).Episodes of severe exacerbation. Throughout the study; 3 months 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.Forced expiratory volume in 1 second (litres) 3 months Forced expiratory volume in 1 second (% predicted) 3 months Forced vital capacity (litres) 3 months VAS scale for sputum production 3 months 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).VAS scale for sleep perturbation 3 months 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).The modified medical research council (mMRC) dyspnoea scale 3 months Scores range from 0 (none) to 4 (very severe).
The St George Respiratory Questionnaire 3 months Scores range from 0 to 100, with higher scores indicating more limitations.
Six minute walking tests 3 months Oxygen needs (litres/min) during initial hospitalisation At hospital discharge (expected maximum of 28 days) Mode of pre-hospitalization living arrangements Baseline (day 0) At home, rehabilitation centre, assisted living centre, or other
Hospital discharge modality At hospital discharge (expected maximum of 28 days) At home, rehabilitation centre, assisted living centre, or other
Episodes of emergency department use Throughout the study; 3 months Mortality/survival Throughout the study; 3 months The Breathlessness, Cough and Sputum Scale 3 months Symptoms are evaluated on a 5-point Likert-type scale ranging from 0 to 4, with higher scores indicating more severe symptoms.
The Euroqol (EQ-5D-5L) questionnaire 3 months 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.
Trial Locations
- Locations (21)
Clinique du Parc
🇫🇷Castelnau-le-Lez, France
CHU Montpellier
🇫🇷Montpellier, France
Hôpital Nord Franche-Comté
🇫🇷Trévenans, France
APHP - Hôpital Cochin
🇫🇷Paris, France
Centre hospitalier intercommunal de Créteil
🇫🇷Créteil, France
CHU Brest - Hôpital Caval Blanche
🇫🇷Brest, France
APHM - Hôpital Nord
🇫🇷Marseille, France
CHU Nancy
🇫🇷Nancy, France
CH Libourne
🇫🇷Libourne, France
CHRU Lille
🇫🇷Lille, France
CHU Reims
🇫🇷Reims, France
APHP - Hopital Européen Georges Pompidou
🇫🇷Paris, France
APHP - Hôpital Universitaire Pitié-Salpétrière
🇫🇷Paris, France
CHU Nîmes
🇫🇷Nîmes, France
Hospice Civils de Lyon
🇫🇷Lyon, France
APHP - Hôpital BICHAT
🇫🇷Paris, France
CH Roubaix
🇫🇷Roubaix, France
Hôpital Larrey CHU Toulouse
🇫🇷Toulouse, France
CHRU Strasbourg
🇫🇷Strasbourg, France
CHU Amiens
🇫🇷Amiens, France
CHU Bordeaux - Hôpital Haut Lévêque
🇫🇷Pessac, France