Chronic Obstructive Pulmonary Disease
Conditions
Brief summary
The main objective of this study is to determine if the systemic (intravenous) administration of corticosteroids, as compared to placebo, increases the number of ventilator-free days (VFD) and alive at day 28 in COPD patients admitted to an ICU, a step-up unit or a respiratory care unit for an ACRF requiring ventilatory support, either invasive or non-invasive.
Interventions
DRUGMethylprednisolone
In the experimental group, methylprednisolone will be administered intravenously for 5 days at a dose of 1 mg/kg/day. Methylprednisolone will be provided for reconstitution and dilution in 50 ml of NaCl 0.9% solution and administered over 15 minutes, once a day.
DRUGPlacebos
in the control group, placebo will be administered intravenously for 5 days. Placebo will be identical (color and aspect) to experimental substance, will be provide as a 50 mL of NaCl 0.9% solution and administered intravenously over 15 minutes, once a day.
Sponsors
Versailles Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients aged ≥ 40 years 2. Strongly suspected or documented COPD, defined by the presence of the following criterias: * Persistent respiratory symptoms (dyspnoea, chronic cough or sputum) * History of exposure to a risk factor such as tobacco smoke * If available, pulmonary function tests showing airflow limitation not fully reversible (post-bronchodilator ratio of FEV1/ FVC ratio \< 0.7) 3. ACRF, defined by the presence of the two following criteria: * COPD exacerbation defined by a change in the patient baseline respiratory symptoms at least 24 hours and requiring a change in regular respiratory medication * Acute respiratory failure \<24h (polypnea ≥ 30 breaths.min-1 or use of accessory respiratory muscles) requiring ventilatory support, either invasive (implemented because of respiratory distress) or NIV (implemented because of hypercapnic acidosis with PaCO2 ≥ 45 mmHg and pH ≤ 7.35). 4. Admission to an ICU, a step-up unit or a respiratory care unit 5. Inform consent from the patient or his surrogates. In patients who are not able to consent on admission an emergency inclusion procedure will be allowed, with a mandatory delayed consent. 6. Affiliation to (or benefit from) French health insurance system
Exclusion criteria
* Previous diagnostic of asthma, according to GINA international guidelines (40) * Recent use of systemic corticosteroids, defined by systemic corticosteroids use in the past 7 days * Contra-indication of systemic corticosteroids treatment: allergy to corticosteroids, uncontrolled severe arterial hypertension, uncontrolled diabetes mellitus, gastro-intestinal ulcer bleeding * Pneumothorax at randomization * Extracorporeal life support (ECMO or ECCO2R) at inclusion * Moribund patient life expectancy \< 3 months * Pregnancy * Patients protected by law * Exclusion period due to other interventional clinical trial enrolment which can influence primary outcome * Previous inclusion in the present study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the number of ventilator-free days (VFD) and alive at day 28. | day 28 | To determine if the systemic administration of corticosteroids, as compared to placebo, increases the number of ventilator-free days (VFD) and alive at day 28 in COPD patients admitted to an ICU, a step-up unit or a respiratory care unit for an ACRF requiring ventilatory support, either invasive or non-invasive. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of NIV and of invasive mechanical ventilation | at day 90 | Duration of Non Invasive Ventilation and of invasive mechanical ventilation |
| Circulatory and renal support-free days and alive at day 28 | at day 28 | Circulatory and renal support-free days and alive at day 28 |
| Severe hyperglycemia requiring intravenous insulin during the five first days | during the five first days | Severe hyperglycemia requiring intravenous insulin during the five first days |
| Gastro-intestinal bleeding | between inclusion and day 28 | acute loss of 2 g/dL of hemoglobin requiring red blood cell transfusion or gastroscopic evaluation |
| Uncontrolled arterial hypertension | between inclusion and day 28 | unusual hypertension requiring to introduce/add antihypertensive medication (compared to usual medications) |
| ICU acquired weakness (MRC-score < 48/60) assessed on day 28 or at the time of ICU discharge | at day 28 | Intensive Care Unit acquired weakness (MRC-score \< 48/60) assessed on day 28 or at the time of ICU discharge |
| ICU-acquired infections (especially Ventilator-Associated Pneumonia) | at the time of ICU discharge or day 90 | Intensive Care Unit -acquired infections (especially Ventilator-Associated Pneumonia) |
| NIV failure rate | day 7 | NIV failure rate, defined by intubation within day 7 |
| ICU and hospital mortality | between inclusion and day 28 or day 90 | ICU and hospital mortality |
| Day 28 and Day 90 mortality | at Day 28 and Day 90 | Day 28 and Day 90 mortality |
| Standardized mortality ratio (SMR) | between inclusion and day 90 | Standardized mortality ratio (SMR) |
| Number of new exacerbation(s)/hospitalization(s) between hospital discharge and Day 90 | at day 90 | Number of new exacerbation(s)/hospitalization(s) between hospital discharge and Day 90 |
| Dyspnea (patient reported outcome) at Day 90 evaluated by clinical assessment test and dyspnea mMRC score | at day 90 | Dyspnea (patient reported outcome) at Day 90 evaluated by clinical assessment test and dyspnea mMRC score |
| respiratory comfort (patient reported outcome) at Day 90 evaluated by clinical assessment test and dyspnea mMRC score | at day 90 | respiratory comfort (patient reported outcome) at Day 90 evaluated by clinical assessment test and dyspnea mMRC score |
| Length of ICU and hospital stay | at day 90 | Length of ICU and hospital stay |
Countries
France
Contacts
Primary Contactvirginie chatagner
Outcome results
None listed