Clinical trial NCT05546606: CO2 Removal in Severe Acute exacerbatIons of Chronic Obstructive Lung Diseases
Official title: CO2 Removal in Severe Acute exacerbatIons of Chronic Obstructive Lung Diseases
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: COPD Acute Exacerbation
Keywords: ECCO2R
COPD
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
name: Xenios AG
First posted: 2022-09-21
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, multi-centre, randomized, controlled, open-label
Primary purpose: OTHER

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.

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:

  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.

Primary outcomes:
measure: Mortality rate
timeFrame: Up to 60 days
Secondary outcomes:
measure: Invasive Ventilator-free days (IVFDs)
timeFrame: at 28 and 60 days
measure: Ventilator-free days (VFDs), including both IVFDs and non-invasive ventilator-free days (NIV-VFDs)
timeFrame: at 28 and 60 days
measure: 28 day, 90 day, 180 day and 1 year all-cause mortality rate
timeFrame: Up to 1 year
measure: Length of ECCO2R therapy
timeFrame: Up to 28 days
measure: Proportion of patients without intubation and IMV (intubation and IMV avoided)
timeFrame: Up to 28 days
measure: Number of days with active mobilization (outside the bed)
timeFrame: Up to 28 days
measure: Rate of inability to wean from IMV
timeFrame: at Day 28 and Day 60
measure: Rate of ventilator associated pneumonia
timeFrame: at Day 28 and Day 60
measure: Rate of central venous catheter infection
timeFrame: Up to 28 days
measure: Rate of deep venous thrombosis
timeFrame: Up to 28 days
measure: Rate of vascular injury caused by cannulation
timeFrame: Up to 28 days
measure: Rate of severe bleeding (any cause)
timeFrame: Up to 28 days
measure: Rate of severe hemolysis
timeFrame: Up to 28 days
measure: Rate of heparin-induced thrombocytopenia - type II
timeFrame: Up to 28 days
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
city: Besançon
country: France
facility: CHU Besançon
city: Bobigny
country: France
facility: Hôpital Avicennes, AP-HP
city: La Roche-sur-Yon
country: France
facility: CHD de Vendée
city: Le Mans
country: France
facility: CH Le Mans
city: Lyon
country: France
facility: Hôpital de la Croix-Rousse
city: Marseille
country: France
facility: Hôpital Nord
city: Montpellier
country: France
facility: CHU Lapeyronie
city: Orléans
country: France
facility: CHR Orléans
city: Paris
country: France
facility: Hôpital La Pitié Salpêtrière, AP-HP
city: Paris
country: France
facility: Hôpital Cochin - APHP
city: Paris
country: France
facility: Hôpital européen Georges Pompidou - APHP
city: Paris
country: France
facility: Hôpital Tenon
city: Poitiers
country: France
facility: CHU la Milétrie
city: Rennes
country: France
facility: CHU Pontchaillou
city: Rouen
country: France
facility: CHU Rouen
city: Saint Denis
country: France
facility: Centre Hospitalier de Saint Denis
city: Strasbourg
country: France
facility: Nouvel Hôpital Civil Strasbourg
city: Tours
country: France
facility: CHRU Bretonneau
city: Villenave-d'Ornon
country: France
facility: Hôpital d'Instruction des Armées Robert Picqué
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Jean-Luc MD Diehl, PhD
role: PRINCIPAL_INVESTIGATOR
References: