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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier De Versailles

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

8 Oct 2021 → ongoing

Decision date (initial)

2024-09-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-516651-41-00

EudraCT number

2019-001726-99

ClinicalTrials.gov

NCT04163536

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

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 objectives 5

1. Evaluate the effect of corticosteroids administration, as compared to placebo on mechanical ventilation and support
2. Evaluate the effect of corticosteroids administration, as compared to placebo on side effects of corticosteroids
3. Evaluate the effect of corticosteroids administration, as compared to placebo on lenght of stay
4. Evaluate the effect of corticosteroids administration, as compared to placebo on mortality
5. Evaluate the effect of corticosteroids administration, as compared to placebo on COPD exacerbations case

Conditions and MedDRA coding

COPD : chronic obstructive Pulmonary disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients aged ≥ 40 years, man or woman
2. Strongly suspected or documented COPD defined by all the following criterias : - Persistent respiratory symptoms (dyspnoea, chronic cough or sputum production) - History of exposure to a risk factor such as tobacco smoke - If available, pulmonary function tests showing airflow limitation that is not fully reversible (post-bronchodilator ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio < 0.7)
3. Severe acute exacerbation, defined by the presence of the two following criteria: - COPD exacerbation defined by a change in the patient baseline respiratory symptoms: dyspnoea, cough or sputum (volume or purulence) and requiring a change in regular respiratory medication - Acute respiratory failure (defined by clinical signs of excessive muscle activity: polypnea ≥ 30 breaths /min or use of accessory respiratory muscles) requiring mechanical ventilation (possibly already started <24H), either invasive 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 <24h
5. Written Informed consent from the patient or his surrogates. In patients who are not able to consent on admission (i.e., because of hypercapnic encephalopathy) and in absence of a substitute decision maker, an emergency inclusion procedure will be allowed, with a mandatory delayed consent
6. Affiliation to (or benefit from) French health insurance system.

Exclusion criteria 11

1. Previous diagnostic of asthma, according to "GINA" international guidelines
2. current and proven SARS-COV2 infection
3. Contra-indication of systemic corticosteroids treatment: allergy to corticosteroids, uncontrolled severe arterial hypertension, uncontrolled diabetes mellitus, gastro-intestinal ulcer bleeding
4. underlying disease requiring chronic daily use of systemic steroids
5. Pneumothorax at inclusion
6. Extracorporeal life support (ECMO or ECCO2R) at randomization
7. Moribund patient life expectancy < 3 months
8. Pregnancy
9. Patients protected by law
10. Exclusion period due to other interventional clinical trial enrolment which can influence primary outcome
11. Previous inclusion in the present study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of ventilator-free days (VFD) and alive.

Secondary endpoints 14

1. NIV failure rate, defined by intubation
2. Duration of NIV and of invasive mechanical ventilation
3. Circulatory support-free days and alive at day 28
4. Severe hyperglycemia requiring intravenous insulin before day 5
5. Gastro-intestinal bleeding: acute loss of 2 g/dL of hemoglobin requiring red blood cell transfusion or gastroscopic evaluation
6. Uncontrolled arterial hypertension: unusual hypertension requiring to introduce/add antihypertensive medication (compared to usual medications)
7. ICU acquired weakness (MRC-score) assessed on day 28 or at the time of ICU discharge
8. ICU-acquired infections (especially Ventilator-Associated Pneumonia)
9. Length of ICU and hospital stay
10. ICU and hospital mortality
11. Day 28 and Day 90 mortality
12. Standardized mortality ratio (SMR)
13. Number of new exacerbation(s)/hospitalization(s) between hospital discharge and Day 90
14. Dyspnea and comfort (patient reported outcome) at Day 90

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier De Versailles

Sponsor organisation

Centre Hospitalier De Versailles

Address

177 Rue De Versailles, Le Chesnay Le Chesnay

City

Le Chesnay Rocquencourt

Postcode

78150

Country

France

Scientific contact point

Organisation

Centre Hospitalier De Versailles

Contact name

project manager

Public contact point

Organisation

Centre Hospitalier De Versailles

Contact name

project manager

Locations

1 EU/EEA country · 26 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications