Comparison of Corticosteroids vs Placebo on Duration of Ventilatory Support During Severe Acute Exacerbations of COPD Patients in the ICU

Phase 3

Recruiting

• Conditions: Chronic Obstructive Pulmonary Disease
• Interventions: Drug: Methylprednisolone; Drug: Placebos

• Registration Number: NCT04163536
• Lead Sponsor: Versailles Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-10-29
• Study First Submitted QC: 2019-11-12
• Study First Posted: 2019-11-14
• Study Start: 2021-10-25
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-16
• Last Update Posted: 2023-10-18
• Primary Completion: 2025-10-25
• Study Completion: 2026-03-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 440

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
cortisteroids arm	Methylprednisolone	-
placebo arm	Placebos	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
NIV failure rate	day 7	NIV failure rate, defined by intubation within day 7
Duration of NIV and of invasive mechanical ventilation	at day 90	Duration of Non Invasive Ventilation and of invasive mechanical ventilation
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
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
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
Uncontrolled arterial hypertension	between inclusion and day 28	unusual hypertension requiring to introduce/add antihypertensive medication (compared to usual medications)
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)
Gastro-intestinal bleeding	between inclusion and day 28	acute loss of 2 g/dL of hemoglobin requiring red blood cell transfusion or gastroscopic evaluation
Length of ICU and hospital stay	at day 90	Length of ICU and hospital stay
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

Trial Locations

Locations (23)

CHU Angers; 🇫🇷 Angers, France

CHU Louis Mourier; 🇫🇷 Colombes, France

CHRU lille; 🇫🇷 Lille, France

CHU Lyon; 🇫🇷 Lyon, France

CHRU Tours; 🇫🇷 Tours, France

André Mignot Hospital, Intensive care unit; 🇫🇷 Le Chesnay, Les Yvelines, France

CH métropole savoie; 🇫🇷 Chambéry, France

CHU Henri mondor; 🇫🇷 Créteil, France

CHU Dijon; 🇫🇷 Dijon, France

CHU Grenoble; 🇫🇷 Grenoble, France

CHD Vendée; 🇫🇷 La Roche-sur-Yon, France

CHU de Bicêtre; 🇫🇷 Le Kremlin-Bicêtre, France

CH Le Mans; 🇫🇷 Le Mans, France

CH d'Annecy Genevois; 🇫🇷 Metz-Tessy, France

CHR orléans; 🇫🇷 Orléans, France

CHU Nantes; 🇫🇷 Nantes, France

CHU Cochin; 🇫🇷 Paris, France

Pitié-Salpêtrière; 🇫🇷 Paris, France

Hôpital européen Georges pompidou; 🇫🇷 Paris, France

CHU Poitiers; 🇫🇷 Poitiers, France

CHU de Rennes; 🇫🇷 Rennes, France

CHU de Rouen; 🇫🇷 Rouen, France

Hopital Foch; 🇫🇷 Suresnes, France