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The study aims to investigate if veno-venous (vv)-extracorporeal carbon dioxide Removal (ECCO2R) is capable of reducing mortality and/or severe disability at day 60 after randomisation in patients with severe acute exacerbation of chronic obstructive pulmonary disease (COPD) requiring invasive mechanical ventilation (IMV). Extubation will be facilitated by VV-ECCO2R and compared to IMV alone in a randomized controlled trial.

The current study hypothesizes an advantage for veno-venous extracorporeal carbon dioxide removal (VV-ECCO2R) in severe acute exacerbation of COPD requiring invasive mechanical ventilation (IMV) to facilitate early extubation in terms of reducing mortality or severe disability. The study hypothesizes that avoiding IMV could reduce mortality and substantially improve quality of life, especially in regard to avoidance of tracheostomy and long-term home IMV. Improvement in mobility due to sooner recovery has a further major impact on patients' QoL.

After randomization patients with acute exacerbation of severe COPD, requiring invasive mechanical ventilation will be treated either with conventional care or VV-ECCO2R to facilitate early extubation. VV-ECCO2R is used in a standard configuration with either double lumen cannula (22-24Fr) or two small single vessel cannulas (15-19 Fr), allowing a blood flow rate between 1-1.75 L/min.

Conventional care in the control arm includes invasive mechanical ventilation and the attempt to extubate the patient as early as possible and to switch to non-invasive ventilation (NIV). If extubation fails, tracheostomy can be performed according to the discretion of the treating physician.

Inclusion Criteria:

1. Informed consent signed and dated by the investigator; and

   1. if patient is able to give consent: by the study patient
   2. if patients unable to give consent: by the legal representative or
   3. if an emergency situation is determined: by an independent consultant physician.

2. Minimum age of 18 years

3. In case of female patients:

   1. Postmenopausal status defined as I. Prior bilateral oophorectomy Or II. Age ≥60 years Or if Age is <60 years or cannot be determined
   2. A negative pregnancy test, defined as negative beta hCG test with a hCG level <5 mIU/mL.

4. Known History of COPD

5. Acute exacerbation of COPD requiring invasive mechanical ventilation

6. Failed extubation attempt or extubation not possible within 24 hours after intubation

7. Acute and potentially reversible cause of respiratory failure as determined by the treating physician

Exclusion Criteria:

1. Any conditions which could interfere with the patient's ability to comply with the study
2. In case of female patients: pregnancy and lactation period
3. Participation in any interventional clinical study during the preceding 30 days
4. Platelets <70.000/µl at baseline
5. Previous participation in the X-COPD study
6. Endotracheally intubated and mechanically ventilated for >96 hours prior to randomization
7. Acute liver failure, defined by an international normalized ratio (INR) >2 without anticoagulation and/or bilirubin >4 mg/dL (>68 μmol/L) and/or hepatic encephalopathy (all three apply)
8. PaO2/FiO2 ratio <120 mmHg measured with FiO2 of 1.0
9. Expectation of disease progression leading to high-flow extracorporeal membrane oxygenation (ECMO) treatment
10. Cerebral haemorrhage
11. Tracheostomy
12. Estimated life expectancy <6 months due to reasons other than COPD
13. Acute ischemic stroke
14. Contraindication to anticoagulation
15. Severe chronic liver disease (Child Pugh C)
16. Acute pulmonary embolism requiring thrombolytic therapy
17. Acute or chronic heart failure with left ventricular ejection fraction <30%
18. Acute or chronic renal failure requiring dialysis
19. Organ transplantation or immunosuppression due to ongoing immunosuppressive medication or neutropenia for instance following organ transplantation or anticancer therapy
20. Neuromuscular disorder or chronic restrictive lung disease affecting native lung ventilation
21. Known Heparin induced thrombocytopenia type II
22. Acute coronary syndrome and myocardial infarction
23. Obesity hypoventilation syndrome
24. BMI >40
25. Patient not expected to survive 48 hours
26. Do not resuscitate (DNR) order