CO2 Removal in Severe Acute exacerbatIons of Chronic Obstructive Lung Diseases

COPD Acute Exacerbation Clinical Trial

— CORAIL  

Official title:

CO2 Removal in Severe Acute exacerbatIons of Chronic Obstructive Lung Diseases

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05546606
• Other study ID #: P150913J
• Secondary ID: 2022-A01343-40PH
• Status: Recruiting
• Phase: N/A
• Start date: April 18, 2023
• Est. completion date: April 18, 2026

Study information

• Verified date: September 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Joséphine Braun
• Phone: 01 44 84 17 38
• Email: josephine.braun[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to determine which standard of care strategy will best benefit very severe Acute Exacerbation (AE) of Chronic Obstructive Pulmonary Disease (COPD), single versus reinforced with ECCO2R and assess the respective efficacy and the safety. Very severe AE of COPD will be defined by high risk of Non-Invasive Ventilation (NIV) failure defined by need of intubation and/or in-Intensive Care Unit (ICU) mortality (Stratum 1) or by Invasive Mechanical Ventilation (IMV) after NIV failure and/or with severe hyperinflation and hypercapnia (Stratum 2).

Description:

After inclusions, all patients from Stratum 1 (at high risk of NIV failure) and Stratum 2 (Intubation-IMV) will be randomly assigned to the single standard of care treatment or to the strengthen standard treatment reinforced with ECCO2R . Weaning of IMV in the strengthen standard of care group will precede weaning of ECCO2R. Weaning of NIV in the strengthen standard of care group will precede weaning of ECCO2R, except for patients with long-term NIV. The patients will undergo a maximum of 33 visits over the 1-year study duration, split in 3 successive periods: selection period, treatment period (until the discharge of the ICU or day 28 after randomisation), follow-up period after the discharge of the ICU (or after day 28) up to 1 year (after randomisation).

Selection period: before randomisation, demographics, medical and surgical history, clinical examination (including physical examination, respiration rate, encephalopathy score, sedation score, pain assessment, Simplified Acute Physiology Score 2, central body temperature, systolic and diastolic blood pressures, heart rate), blood sampling, electrocardiogram and ventilator parameters will be recorded.

Follow-up period: ECCO2R will start as soon as possible after randomisation in patients allocated to the strengthen standard of care group. All patients will be evaluated 12 + 2 hours after randomisation, followed by a daily visit with the collection of the following data if applicable: clinical examination, ECCO2R parameters, ventilator parameters, concomitant medications (including sedative drugs), occurrence of adverse events, date, time and criteria if endotracheal intubation (stratum 1). Arterial blood gases, hematology and serum biochemistry parameters will be assayed daily.

End of Research period: all patients will be evaluated at day 60 (+ 7 days), Day 90 (+ 7 days), Day 180 (+ 7 days) and 1 year (+ 7 days) at least by phone contact, with collection of: vital status, functional status (Severely Disabled or not, Katz Index of Independence in Activities of Daily Living), date of ICU discharge (if > Day 28), date of hospital discharge, occurrences of ICU re-admissions, of adverse events, type and length of mechanical ventilation needed if applicable.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 304
• Est. completion date: April 18, 2026
• Est. primary completion date: June 18, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years

• Known or suspected diagnosis of COPD based on clinical history, pulmonary function test when available, arterial blood gases, physical examination, and chest radiograph

• Worsening dyspnea for < 2 weeks

• Written informed consent signed by patients or their surrogates, with possibility of an emergency procedure with deferred consent

• Patient affiliated to a Social Security System (excluding "AME: aide médicale d'état")

• Negative serum or urinary ß-hCG for women of child-bearing potential

• Very severe AE criteria defined either by:

1. Stratum 1: high likelihood of NIV failure defined by PaCO2 > 55 mmHg and pH < 7.25, either at baseline and/or after at least one hour of NIV

2. Stratum 2: intubation and IMV since less than 72 hrs, either after NIV failure and/or with pH < 7.30 and PaCO2 > 55 mmHg and PEEPi (end-expiratory occlusion) > 5 cmH2O, while on Assist-Controlled Ventilation with the following parameters: VT: 8 ml/kg, RR: 12/min., applied PEEP: 0 cmH2O

Exclusion Criteria:

• Hemodynamic instability

• Known allergy to heparin or to any of the excipients of the specialty used

• Contra-indications to heparin listed in the SmPC of the specialty used.

• History of type II Heparin-induced thrombocytopenia

• Thrombocytopenia (platelets < 100.000/mm3)

• Recent major surgery

• Haemorrhagic disorders such as:

• Organic lesion likely to bleed

• Bleeding manifestations or tendencies linked to disorders of hemostasis

• Intracerebral hemorrhage

• Uncontrolled arrhythmia

• Bleeding diathesis

• Body Mass Index > 35 kg/m2

• PaO2/FiO2 < 180 mmHg

• Do not intubate order

• Fibrosing idiopathic interstitial pneumonitis (based on the available medical files)

• Neuromuscular diseases (based on the available medical files)

• Patients with tracheotomy

• Patients with severe concomitant chronic systemic disease with a limited probability of survival (< 6 months)

• Severely disabled (confinement to bed and inability to wash or dress alone) patients before AE

• Pregnant woman

• Participation in another interventional study involving human participants up to their ICU discharge, whether the studies include an investigational medical device, or being in the exclusion period at the end of a previous study.

Related Conditions & MeSH terms

• COPD Acute Exacerbation
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Device:
• ECCO2R
ECCO2R therapy using the Xenios platform, CE-marked medical device of the firm Xenios AG (Heilbronn, Germany), including the following components: Xenios console, iLA active iLA Kit IPS and Novaport Twin (18Fr, 22Fr or 24 Fr) cannulas The maximal duration of ECCO2R therapy with one circuit will be of 29 days in agreement with the regulatory approval of the patient kit.

Locations

Country	Name	City	State
France	CHU Angers	Angers
France	CHU Besançon	Besançon
France	Hôpital Avicennes, AP-HP	Bobigny
France	CHD de Vendée	La Roche-sur-Yon
France	CH Le Mans	Le Mans
France	Hôpital de la Croix-Rousse	Lyon
France	Hôpital Nord	Marseille
France	CHU Lapeyronie	Montpellier
France	CHR Orléans	Orléans
France	Hôpital Cochin - APHP	Paris
France	Hôpital européen Georges Pompidou - APHP	Paris
France	Hôpital La Pitié Salpêtrière, AP-HP	Paris
France	Hôpital Tenon	Paris
France	CHU la Milétrie	Poitiers
France	CHU Pontchaillou	Rennes
France	CHU Rouen	Rouen
France	Centre Hospitalier de Saint Denis	Saint Denis
France	Nouvel Hôpital Civil Strasbourg	Strasbourg
France	CHRU Bretonneau	Tours
France	Hôpital d'Instruction des Armées Robert Picqué	Villenave-d'Ornon

Sponsors (3)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Ministry of Health, France, Xenios AG

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality rate	To determine the best strategy between strengthen standard of care reinforced with ECCO2R, versus single standard of care,	Up to 60 days
Secondary	Invasive Ventilator-free days (IVFDs)	To assess the efficacy of ECCO2R, based on the time on IMV	at 28 and 60 days
Secondary	Ventilator-free days (VFDs), including both IVFDs and non-invasive ventilator-free days (NIV-VFDs)	To assess the efficacy of ECCO2R, based on the time on IMV	at 28 and 60 days
Secondary	28 day, 90 day, 180 day and 1 year all-cause mortality rate	To assess the efficacy of ECCO2R, based on the all-cause mortality	Up to 1 year
Secondary	Length of ECCO2R therapy	To assess the efficacy of ECCO2R, based on ECCO2R device's performance	Up to 28 days
Secondary	Proportion of patients without intubation and IMV (intubation and IMV avoided)	To assess the efficacy of ECCO2R, based on intubation rate	Up to 28 days
Secondary	Number of days with active mobilization (outside the bed)	To assess the efficacy of ECCO2R, based on the ability to actively mobilize the patients	Up to 28 days
Secondary	Rate of inability to wean from IMV	To assess the safety, based on central venous catheter-related complications	at Day 28 and Day 60
Secondary	Rate of ventilator associated pneumonia	To assess the safety, based on central venous catheter-related complications	at Day 28 and Day 60
Secondary	Rate of central venous catheter infection	To assess the safety, based on ECCO2R-related complications,	Up to 28 days
Secondary	Rate of deep venous thrombosis	To assess the safety, based on ECCO2R-related complications,	Up to 28 days
Secondary	Rate of vascular injury caused by cannulation	To assess the safety, based on ECCO2R-related complications,	Up to 28 days
Secondary	Rate of severe bleeding (any cause)	To assess the safety, based on ECCO2R-related complications,	Up to 28 days
Secondary	Rate of severe hemolysis	To assess the safety, based on ECCO2R-related complications,	Up to 28 days
Secondary	Rate of heparin-induced thrombocytopenia - type II	To assess the safety, based on ECCO2R-related complications,	Up to 28 days