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

Versailles Hospital23 sites in 1 country440 target enrollmentOctober 25, 2021

ConditionsChronic Obstructive Pulmonary Disease

InterventionsMethylprednisolone Placebos

DrugsMethylprednisolone Placebos

Overview

Phase: Phase 3
Intervention: Methylprednisolone
Conditions: Chronic Obstructive Pulmonary Disease
Sponsor: Versailles Hospital
Enrollment: 440
Locations: 23
Primary Endpoint: the number of ventilator-free days (VFD) and alive at day 28.
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

October 25, 2021

End Date

March 1, 2026

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Versailles Hospital

Responsible Party

Principal Investigator

Alexis FERRE

coordinating investigator

Versailles Hospital

Eligibility Criteria

Inclusion Criteria

•Patients aged ≥ 40 years
•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)
•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).
•Admission to an ICU, a step-up unit or a respiratory care unit
•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.

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

Arms & Interventions

cortisteroids arm

Intervention: Methylprednisolone

placebo arm

Intervention: Placebos

Outcomes

Primary Outcomes

the number of ventilator-free days (VFD) and alive at day 28.

Time Frame: 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 Outcomes

NIV failure rate(day 7)
Duration of NIV and of invasive mechanical ventilation(at day 90)
Severe hyperglycemia requiring intravenous insulin during the five first days(during the five first days)
ICU acquired weakness (MRC-score < 48/60) assessed on day 28 or at the time of ICU discharge(at day 28)
Circulatory and renal support-free days and alive at day 28(at day 28)
Uncontrolled arterial hypertension(between inclusion and day 28)
ICU-acquired infections (especially Ventilator-Associated Pneumonia)(at the time of ICU discharge or day 90)
Gastro-intestinal bleeding(between inclusion and day 28)
Length of ICU and hospital stay(at day 90)
ICU and hospital mortality(between inclusion and day 28 or day 90)
Day 28 and Day 90 mortality(at Day 28 and Day 90)
Standardized mortality ratio (SMR)(between inclusion and day 90)
Number of new exacerbation(s)/hospitalization(s) between hospital discharge and Day 90(at day 90)
Dyspnea (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(at day 90)