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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Methylprednisolone; Drug: Placebos

• Study Type: Interventional
• Enrollment (Estimated): 440
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: virginie chatagner; Phone Number: 0139239776; Email: vchatagner@ght78sud.fr

Study Locations

• France
  • Angers, France
    • Recruiting
    • Chu Angers
    • Principal Investigator: françois beloncle
  • Chambéry, France
    • Not yet recruiting
    • CH Metropole Savoie
    • Principal Investigator: Vincent Peigne
  • Colombes, France
    • Recruiting
    • CHU Louis Mourier
    • Principal Investigator: jean damien ricard
  • Créteil, France
    • Not yet recruiting
    • CHU Henri Mondor
    • Principal Investigator: Armand Mekontso-Dessap
  • Dijon, France
    • Recruiting
    • CHU Dijon
    • Principal Investigator: Jean Pierre Quenot
  • Grenoble, France
    • Recruiting
    • CHU Grenoble
    • Principal Investigator: Nicolas Terzi
  • La Roche-sur-Yon, France
    • Recruiting
    • CHD Vendee
    • Principal Investigator: Gwenhaël Colin
  • Le Kremlin-Bicêtre, France, 94270
    • Recruiting
    • CHU de Bicêtre
    • Principal Investigator: Nadia Anguel
  • Le Mans, France
    • Recruiting
    • CH Le Mans
    • Principal Investigator: Christophe Guitton
  • Lille, France
    • Recruiting
    • CHRU Lille
    • Principal Investigator: Saad NSEIR
  • Lyon, France
    • Recruiting
    • CHU LYON
    • Principal Investigator: Mehdi MEZIDI
  • Metz-Tessy, France, 74370
    • Recruiting
    • CH d'Annecy Genevois
    • Principal Investigator: Michel Muller, Dr
  • Nantes, France
    • Not yet recruiting
    • CHU Nantes
    • Principal Investigator: Jean Reignier
  • Orléans, France
    • Recruiting
    • CHR Orléans
    • Principal Investigator: Toufik Kamel
  • Paris, France
    • Recruiting
    • CHU Cochin
    • Principal Investigator: Jean daniel Chiche
  • Paris, France
    • Recruiting
    • Hopital Europeen Georges Pompidou
    • Principal Investigator: Benjamin Planquette
  • Paris, France
    • Recruiting
    • Pitié-Salpêtrière
    • Principal Investigator: Alexandre Demoule
  • Poitiers, France
    • Recruiting
    • CHU Poitiers
    • Principal Investigator: Arnaud THILLE
  • Rennes, France
    • Recruiting
    • CHU de Rennes
    • Principal Investigator: Arnaud Gacouin
  • Rouen, France
    • Not yet recruiting
    • CHU de Rouen
    • Principal Investigator: Gaëtan Beduneau
  • Suresnes, France
    • Active, not recruiting
    • Hôpital FOCH
  • Tours, France
    • Recruiting
    • CHRU Tours
    • Principal Investigator: Stéphane Ehrmann
  • Les Yvelines
    • Le Chesnay, Les Yvelines, France, 78150
      • Recruiting
      • André Mignot Hospital, Intensive care unit
      • Principal Investigator: Alexis FERRE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo arm	Drug: 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.
Active Comparator: cortisteroids arm	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: Versailles Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2021
• Primary Completion (Estimated): October 25, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: October 29, 2019
• First Submitted That Met QC Criteria: November 12, 2019
• First Posted (Actual): November 14, 2019

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 16, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Chronic Disease; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: P17/15_corticop

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No