Clinical trial NCT04163536: Comparison of Corticosteroids vs Placebo on Duration of Ventilatory Support During Severe Acute Exacerbations of COPD Patients in the ICU
Official title: Comparison of Corticosteroids Versus Placebo on Duration of Ventilatory Support During Severe Acute Exacerbations of COPD Patients in the Intensive Care Unit: a Multicentre Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary Disease
Lead sponsor: Versailles Hospital
Sponsor class: OTHER
First posted: 2019-11-14
Enrollment: 440
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: 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.


Eligibility criteria: 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

Primary outcomes:
measure: the number of ventilator-free days (VFD) and alive at day 28.
timeFrame: day 28
Secondary outcomes:
measure: NIV failure rate
timeFrame: day 7
measure: Duration of NIV and of invasive mechanical ventilation
timeFrame: at day 90
measure: Circulatory and renal support-free days and alive at day 28
timeFrame: at day 28
measure: Severe hyperglycemia requiring intravenous insulin during the five first days
timeFrame: during the five first days
measure: Gastro-intestinal bleeding
timeFrame: between inclusion and day 28
measure: Uncontrolled arterial hypertension
timeFrame: between inclusion and day 28
measure: ICU acquired weakness (MRC-score < 48/60) assessed on day 28 or at the time of ICU discharge
timeFrame: at day 28
measure: ICU-acquired infections (especially Ventilator-Associated Pneumonia)
timeFrame: at the time of ICU discharge or day 90
measure: Length of ICU and hospital stay
timeFrame: at day 90
measure: ICU and hospital mortality
timeFrame: between inclusion and day 28 or day 90
measure: Day 28 and Day 90 mortality
timeFrame: at Day 28 and Day 90
measure: Standardized mortality ratio (SMR)
timeFrame: between inclusion and day 90
measure: Number of new exacerbation(s)/hospitalization(s) between hospital discharge and Day 90
timeFrame: at day 90
measure: Dyspnea (patient reported outcome) at Day 90 evaluated by clinical assessment test and dyspnea mMRC score
timeFrame: at day 90
measure: respiratory comfort (patient reported outcome) at Day 90 evaluated by clinical assessment test and dyspnea mMRC score
timeFrame: at day 90
Other outcomes:
Locations:
city: Le Chesnay
country: France
facility: André Mignot Hospital, Intensive care unit
state: Les Yvelines
city: Angers
country: France
facility: CHU Angers
city: Chambéry
country: France
facility: CH métropole savoie
city: Colombes
country: France
facility: CHU Louis Mourier
city: Créteil
country: France
facility: CHU Henri mondor
city: Dijon
country: France
facility: CHU Dijon
city: Grenoble
country: France
facility: CHU Grenoble
city: La Roche-sur-Yon
country: France
facility: CHD Vendée
city: Le Kremlin-Bicêtre
country: France
facility: CHU de Bicêtre
city: Le Mans
country: France
facility: CH Le Mans
city: Lille
country: France
facility: CHRU lille
city: Lyon
country: France
facility: CHU Lyon
city: Metz-Tessy
country: France
facility: CH d'Annecy Genevois
city: Nantes
country: France
facility: CHU Nantes
city: Orléans
country: France
facility: CHR orléans
city: Paris
country: France
facility: CHU Cochin
city: Paris
country: France
facility: Hôpital européen Georges pompidou
city: Paris
country: France
facility: Pitié-Salpêtrière
city: Poitiers
country: France
facility: CHU Poitiers
city: Rennes
country: France
facility: CHU de Rennes
city: Rouen
country: France
facility: CHU de Rouen
city: Suresnes
country: France
facility: Hopital Foch
city: Tours
country: France
facility: CHRU Tours
Study officials:
References: