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

Chronic Obstructive Pulmonary Disease Clinical Trial

— Corticop  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04163536
• Other study ID #: P17/15_corticop
• Status: Recruiting
• Phase: Phase 3
• Start date: October 25, 2021
• Est. completion date: March 1, 2026

Study information

• Verified date: October 2023
• Source: Versailles Hospital
• Contact: virginie chatagner
• Phone: 0139239776
• Email: vchatagner[@]ght78sud.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 440
• Est. completion date: March 1, 2026
• Est. primary completion date: October 25, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Methylprednisolone
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.
• Placebos
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.

Locations

Country	Name	City	State
France	CHU Angers	Angers
France	CH métropole savoie	Chambéry
France	CHU Louis Mourier	Colombes
France	CHU Henri mondor	Créteil
France	CHU Dijon	Dijon
France	CHU Grenoble	Grenoble
France	CHD Vendée	La Roche-sur-Yon
France	André Mignot Hospital, Intensive care unit	Le Chesnay	Les Yvelines
France	CHU de Bicêtre	Le Kremlin-Bicêtre
France	CH Le Mans	Le Mans
France	CHRU lille	Lille
France	CHU Lyon	Lyon
France	CH d'Annecy Genevois	Metz-Tessy
France	CHU Nantes	Nantes
France	CHR orléans	Orléans
France	CHU Cochin	Paris
France	Hôpital européen Georges pompidou	Paris
France	Pitié-Salpêtrière	Paris
France	CHU Poitiers	Poitiers
France	CHU de Rennes	Rennes
France	CHU de Rouen	Rouen
France	Hopital Foch	Suresnes
France	CHRU Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Versailles Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the number of ventilator-free days (VFD) and alive at 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.	day 28
Secondary	NIV failure rate	NIV failure rate, defined by intubation within day 7	day 7
Secondary	Duration of NIV and of invasive mechanical ventilation	Duration of Non Invasive Ventilation and of invasive mechanical ventilation	at day 90
Secondary	Circulatory and renal support-free days and alive at day 28	Circulatory and renal support-free days and alive at day 28	at day 28
Secondary	Severe hyperglycemia requiring intravenous insulin during the five first days	Severe hyperglycemia requiring intravenous insulin during the five first days	during the five first days
Secondary	Gastro-intestinal bleeding	acute loss of 2 g/dL of hemoglobin requiring red blood cell transfusion or gastroscopic evaluation	between inclusion and day 28
Secondary	Uncontrolled arterial hypertension	unusual hypertension requiring to introduce/add antihypertensive medication (compared to usual medications)	between inclusion and day 28
Secondary	ICU acquired weakness (MRC-score < 48/60) assessed on day 28 or at the time of ICU discharge	Intensive Care Unit acquired weakness (MRC-score < 48/60) assessed on day 28 or at the time of ICU discharge	at day 28
Secondary	ICU-acquired infections (especially Ventilator-Associated Pneumonia)	Intensive Care Unit -acquired infections (especially Ventilator-Associated Pneumonia)	at the time of ICU discharge or day 90
Secondary	Length of ICU and hospital stay	Length of ICU and hospital stay	at day 90
Secondary	ICU and hospital mortality	ICU and hospital mortality	between inclusion and day 28 or day 90
Secondary	Day 28 and Day 90 mortality	Day 28 and Day 90 mortality	at Day 28 and Day 90
Secondary	Standardized mortality ratio (SMR)	Standardized mortality ratio (SMR)	between inclusion and day 90
Secondary	Number of new exacerbation(s)/hospitalization(s) between hospital discharge and Day 90	Number of new exacerbation(s)/hospitalization(s) between hospital discharge and Day 90	at day 90
Secondary	Dyspnea (patient reported outcome) at Day 90 evaluated by clinical assessment test and dyspnea mMRC score	Dyspnea (patient reported outcome) at Day 90 evaluated by clinical assessment test and dyspnea mMRC score	at day 90
Secondary	respiratory comfort (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