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CO2 Removal in Severe Acute exacerbatIons of Chronic Obstructive Lung Diseases (CORAIL)

Primary Purpose

COPD Acute Exacerbation

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
ECCO2R
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for COPD Acute Exacerbation focused on measuring ECCO2R, COPD

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 β-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.

Sites / Locations

  • CHU AngersRecruiting
  • CHU BesançonRecruiting
  • Hôpital Avicennes, AP-HPRecruiting
  • CHD de VendéeRecruiting
  • CH Le MansRecruiting
  • Hôpital de la Croix-RousseRecruiting
  • Hôpital NordRecruiting
  • CHU LapeyronieRecruiting
  • CHR OrléansRecruiting
  • Hôpital La Pitié Salpêtrière, AP-HPRecruiting
  • Hôpital Cochin - APHPRecruiting
  • Hôpital européen Georges Pompidou - APHPRecruiting
  • Hôpital Tenon
  • CHU la MilétrieRecruiting
  • CHU PontchaillouRecruiting
  • CHU RouenRecruiting
  • Centre Hospitalier de Saint DenisRecruiting
  • Nouvel Hôpital Civil StrasbourgRecruiting
  • CHRU Bretonneau
  • Hôpital d'Instruction des Armées Robert Picqué

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Other

Arm Label

Single standard of care

Strengthen standard of care reinforced with ECCO2R

Arm Description

COPD patients who require respiratory support for severe acute exacerbation (AE), either with NIV or with IMV.

COPD patients who require respiratory support for severe acute exacerbations (AE), either with NIV or with IMV reinforced with ECCO2R

Outcomes

Primary Outcome Measures

Mortality rate
To determine the best strategy between strengthen standard of care reinforced with ECCO2R, versus single standard of care,

Secondary Outcome Measures

Invasive Ventilator-free days (IVFDs)
To assess the efficacy of ECCO2R, based on the time on IMV
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
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
Length of ECCO2R therapy
To assess the efficacy of ECCO2R, based on ECCO2R device's performance
Proportion of patients without intubation and IMV (intubation and IMV avoided)
To assess the efficacy of ECCO2R, based on intubation rate
Number of days with active mobilization (outside the bed)
To assess the efficacy of ECCO2R, based on the ability to actively mobilize the patients
Rate of inability to wean from IMV
To assess the safety, based on central venous catheter-related complications
Rate of ventilator associated pneumonia
To assess the safety, based on central venous catheter-related complications
Rate of central venous catheter infection
To assess the safety, based on ECCO2R-related complications,
Rate of deep venous thrombosis
To assess the safety, based on ECCO2R-related complications,
Rate of vascular injury caused by cannulation
To assess the safety, based on ECCO2R-related complications,
Rate of severe bleeding (any cause)
To assess the safety, based on ECCO2R-related complications,
Rate of severe hemolysis
To assess the safety, based on ECCO2R-related complications,
Rate of heparin-induced thrombocytopenia - type II
To assess the safety, based on ECCO2R-related complications,

Full Information

First Posted
September 15, 2022
Last Updated
September 22, 2023
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Ministry of Health, France, Xenios AG
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1. Study Identification

Unique Protocol Identification Number
NCT05546606
Brief Title
CO2 Removal in Severe Acute exacerbatIons of Chronic Obstructive Lung Diseases
Acronym
CORAIL
Official Title
CO2 Removal in Severe Acute exacerbatIons of Chronic Obstructive Lung Diseases
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 18, 2023 (Actual)
Primary Completion Date
June 18, 2025 (Anticipated)
Study Completion Date
April 18, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Ministry of Health, France, Xenios AG

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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).
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COPD Acute Exacerbation
Keywords
ECCO2R, COPD

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Prospective, multi-centre, randomized, controlled, open-label
Masking
None (Open Label)
Allocation
Randomized
Enrollment
304 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single standard of care
Arm Type
No Intervention
Arm Description
COPD patients who require respiratory support for severe acute exacerbation (AE), either with NIV or with IMV.
Arm Title
Strengthen standard of care reinforced with ECCO2R
Arm Type
Other
Arm Description
COPD patients who require respiratory support for severe acute exacerbations (AE), either with NIV or with IMV reinforced with ECCO2R
Intervention Type
Device
Intervention Name(s)
ECCO2R
Intervention Description
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.
Primary Outcome Measure Information:
Title
Mortality rate
Description
To determine the best strategy between strengthen standard of care reinforced with ECCO2R, versus single standard of care,
Time Frame
Up to 60 days
Secondary Outcome Measure Information:
Title
Invasive Ventilator-free days (IVFDs)
Description
To assess the efficacy of ECCO2R, based on the time on IMV
Time Frame
at 28 and 60 days
Title
Ventilator-free days (VFDs), including both IVFDs and non-invasive ventilator-free days (NIV-VFDs)
Description
To assess the efficacy of ECCO2R, based on the time on IMV
Time Frame
at 28 and 60 days
Title
28 day, 90 day, 180 day and 1 year all-cause mortality rate
Description
To assess the efficacy of ECCO2R, based on the all-cause mortality
Time Frame
Up to 1 year
Title
Length of ECCO2R therapy
Description
To assess the efficacy of ECCO2R, based on ECCO2R device's performance
Time Frame
Up to 28 days
Title
Proportion of patients without intubation and IMV (intubation and IMV avoided)
Description
To assess the efficacy of ECCO2R, based on intubation rate
Time Frame
Up to 28 days
Title
Number of days with active mobilization (outside the bed)
Description
To assess the efficacy of ECCO2R, based on the ability to actively mobilize the patients
Time Frame
Up to 28 days
Title
Rate of inability to wean from IMV
Description
To assess the safety, based on central venous catheter-related complications
Time Frame
at Day 28 and Day 60
Title
Rate of ventilator associated pneumonia
Description
To assess the safety, based on central venous catheter-related complications
Time Frame
at Day 28 and Day 60
Title
Rate of central venous catheter infection
Description
To assess the safety, based on ECCO2R-related complications,
Time Frame
Up to 28 days
Title
Rate of deep venous thrombosis
Description
To assess the safety, based on ECCO2R-related complications,
Time Frame
Up to 28 days
Title
Rate of vascular injury caused by cannulation
Description
To assess the safety, based on ECCO2R-related complications,
Time Frame
Up to 28 days
Title
Rate of severe bleeding (any cause)
Description
To assess the safety, based on ECCO2R-related complications,
Time Frame
Up to 28 days
Title
Rate of severe hemolysis
Description
To assess the safety, based on ECCO2R-related complications,
Time Frame
Up to 28 days
Title
Rate of heparin-induced thrombocytopenia - type II
Description
To assess the safety, based on ECCO2R-related complications,
Time Frame
Up to 28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 β-hCG for women of child-bearing potential Very severe AE criteria defined either by: 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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Joséphine Braun
Phone
01 44 84 17 38
Email
josephine.braun@aphp.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Cléo Bourgeois
Phone
01 56 09 56 38
Email
cleo.bourgeois@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Luc MD Diehl, PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU Angers
City
Angers
ZIP/Postal Code
49933
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alain Mercat, MD
Phone
02 41 35 38 15
Email
AlMercat@chu-angers.fr
First Name & Middle Initial & Last Name & Degree
Alain MD Mercat, PhD
Facility Name
CHU Besançon
City
Besançon
ZIP/Postal Code
25030
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
François Belon, MD
Phone
03 81 66 81 27
Email
fbelon@chu-besançon.fr
First Name & Middle Initial & Last Name & Degree
François MD Belon, PhD
Facility Name
Hôpital Avicennes, AP-HP
City
Bobigny
ZIP/Postal Code
93009
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Johanna Oziel, MD
Phone
01 48 95 52 41
Email
johanna.oziel@aphp.fr
First Name & Middle Initial & Last Name & Degree
Johanna MD Oziel, PhD
Facility Name
CHD de Vendée
City
La Roche-sur-Yon
ZIP/Postal Code
85925
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gwenhael Colin, MD
Phone
02 51 44 60 35
Email
gwenhael.colin@ght85.fr
First Name & Middle Initial & Last Name & Degree
Gwenhael MD Colin, PhD
Facility Name
CH Le Mans
City
Le Mans
ZIP/Postal Code
72000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicolas MD Chudeau, PhD
Phone
02 43 43 24 58
Email
nchudeau@ch-lemans.fr
First Name & Middle Initial & Last Name & Degree
Nicolas MD Chudeau, PhD
Facility Name
Hôpital de la Croix-Rousse
City
Lyon
ZIP/Postal Code
69317
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hodane Yonis, MD
Phone
04 72 10 92 71
Email
hodane.yonis@chu-lyon.fr
First Name & Middle Initial & Last Name & Degree
Hodane MD Yonis, PhD
Facility Name
Hôpital Nord
City
Marseille
ZIP/Postal Code
13015
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christophe Guervilly, MD
Phone
04 91 96 58 42
Email
christophe.guervilly@ap-hm.fr
First Name & Middle Initial & Last Name & Degree
Christophe MD Guervilly, PhD
Facility Name
CHU Lapeyronie
City
Montpellier
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kada Klouche, MD
Phone
04 67 33 84 41
Email
k-klouche@chu-montpellier.fr
First Name & Middle Initial & Last Name & Degree
Kada MD Klouche, PhD
Facility Name
CHR Orléans
City
Orléans
ZIP/Postal Code
45067
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Grégoire Muller, MD
Phone
02 38 22 95 34
Email
gregoire.muller@chr-orleans.fr
First Name & Middle Initial & Last Name & Degree
Grégoire MD Muller, PhD
Facility Name
Hôpital La Pitié Salpêtrière, AP-HP
City
Paris
ZIP/Postal Code
75013
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alain Combes, MD
Phone
01 42 16 38 31
Email
alain.combes@aphp.fr
First Name & Middle Initial & Last Name & Degree
Alain MD Combes, PhD
Facility Name
Hôpital Cochin - APHP
City
Paris
ZIP/Postal Code
75014
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean-Paul Mira, MD
Phone
01 58 41 25 17
Email
jean-paul.mira@aphp.fr
First Name & Middle Initial & Last Name & Degree
Jean-Paul MD Mira, PhD
Facility Name
Hôpital européen Georges Pompidou - APHP
City
Paris
ZIP/Postal Code
75015
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean-Luc Diehl, MD
Phone
01 56 09 32 13
Email
jean-luc.diehl@aphp.fr
First Name & Middle Initial & Last Name & Degree
Jean-Luc MD Diehl, PhD
Facility Name
Hôpital Tenon
City
Paris
ZIP/Postal Code
75020
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clarisse Blayau, MD
Phone
01 56 01 65 07
Email
clarisse.blayau@aphp.fr
First Name & Middle Initial & Last Name & Degree
Clarisse MD Blayau, PhD
Facility Name
CHU la Milétrie
City
Poitiers
ZIP/Postal Code
86021
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arnaud Thille, MD
Phone
05 49 44 43 67
Email
arnaud.thille@chu-poitiers.fr
First Name & Middle Initial & Last Name & Degree
Arnaud MD Thille, PhD
Facility Name
CHU Pontchaillou
City
Rennes
ZIP/Postal Code
35033
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Arnaud Gacouin, MD
Phone
02 99 28 42 87
Email
arnaud.gacouin@chu-rennes.fr
First Name & Middle Initial & Last Name & Degree
Arnaud MD Gacouin, PhD
Facility Name
CHU Rouen
City
Rouen
ZIP/Postal Code
76031
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gaëtan Beduneau, MD
Phone
02 32 88 89 90
Email
Gaetan.Beduneau@chu-rouen.fr
First Name & Middle Initial & Last Name & Degree
Gaëtan MD Beduneau, PhD
Facility Name
Centre Hospitalier de Saint Denis
City
Saint Denis
ZIP/Postal Code
93200
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel Da Silva, MD
Phone
01 42 35 61 07
Email
daniel.silva@ch-stdenis.fr
First Name & Middle Initial & Last Name & Degree
Denis MD Da Silva, PhD
Facility Name
Nouvel Hôpital Civil Strasbourg
City
Strasbourg
ZIP/Postal Code
67091
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julie Helms, MD
Phone
03 69 55 13 69
Email
julie.helms@chru-strasbourg.fr
First Name & Middle Initial & Last Name & Degree
Julie MD Helms, PhD
Facility Name
CHRU Bretonneau
City
Tours
ZIP/Postal Code
37044
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emmanuelle Mercier, MD
Phone
02 47 47 38 55
Email
emmanuelle.mercier@chu-tours.fr
First Name & Middle Initial & Last Name & Degree
Emmanuelle MD Mercier, PhD
Facility Name
Hôpital d'Instruction des Armées Robert Picqué
City
Villenave-d'Ornon
ZIP/Postal Code
33882
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Tran-Van, MD
Phone
05 56 84 74 79
Email
david.tranvan@intradef.gouv.fr
First Name & Middle Initial & Last Name & Degree
David MD Tran-Van, PhD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared
IPD Sharing Time Frame
One year after the last publication
IPD Sharing Access Criteria
Data sharing must be accepted by the sponsor and the PI based on scientific project and scientific involvement of the PI team. The founder could be involved in the decision. Teams wishing obtain IPD must meet the sponsor and IP team to present scientifics (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasibility and financial support will be discussed before mandatory contractualization.

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CO2 Removal in Severe Acute exacerbatIons of Chronic Obstructive Lung Diseases

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