COPD Acute Exacerbation
Conditions
Keywords
ECCO2R, COPD
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.
Interventions
DEVICEECCO2R
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.
Sponsors
Ministry of Health, France
Xenios AG
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Prospective, multi-centre, randomized, controlled, open-label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality rate | Up to 60 days | To determine the best strategy between strengthen standard of care reinforced with ECCO2R, versus single standard of care, |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ventilator-free days (VFDs), including both IVFDs and non-invasive ventilator-free days (NIV-VFDs) | at 28 and 60 days | 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 | Up to 1 year | To assess the efficacy of ECCO2R, based on the all-cause mortality |
| Length of ECCO2R therapy | Up to 28 days | To assess the efficacy of ECCO2R, based on ECCO2R device's performance |
| Proportion of patients without intubation and IMV (intubation and IMV avoided) | Up to 28 days | To assess the efficacy of ECCO2R, based on intubation rate |
| Number of days with active mobilization (outside the bed) | Up to 28 days | To assess the efficacy of ECCO2R, based on the ability to actively mobilize the patients |
| Rate of inability to wean from IMV | at Day 28 and Day 60 | To assess the safety, based on central venous catheter-related complications |
| Invasive Ventilator-free days (IVFDs) | at 28 and 60 days | To assess the efficacy of ECCO2R, based on the time on IMV |
| Rate of central venous catheter infection | Up to 28 days | To assess the safety, based on ECCO2R-related complications, |
| Rate of deep venous thrombosis | Up to 28 days | To assess the safety, based on ECCO2R-related complications, |
| Rate of vascular injury caused by cannulation | Up to 28 days | To assess the safety, based on ECCO2R-related complications, |
| Rate of severe bleeding (any cause) | Up to 28 days | To assess the safety, based on ECCO2R-related complications, |
| Rate of severe hemolysis | Up to 28 days | To assess the safety, based on ECCO2R-related complications, |
| Rate of heparin-induced thrombocytopenia - type II | Up to 28 days | To assess the safety, based on ECCO2R-related complications, |
| Rate of ventilator associated pneumonia | at Day 28 and Day 60 | To assess the safety, based on central venous catheter-related complications |
Countries
France
Outcome results
None listed