Early Extubation by ECCO2R Compared to IMV in Patients With Severe Acute Exacerbation of COPD

COPD Exacerbation Clinical Trial

— X-COPD  

Official title:

A Multicentre, Randomized-controlled Trial of EXtracorporeal CO2 Removal to Facilitate Early Extubation Compared to Invasive Mechanical Ventilation in Patients With Severe Acute Exacerbation of COPD (X-COPD)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03584295
• Other study ID #: COPD-ECCO2R-01-INT
• Status: Recruiting
• Phase: N/A
• Start date: February 7, 2023
• Est. completion date: March 2026

Study information

• Verified date: February 2024
• Source: Fresenius Medical Care Deutschland GmbH
• Contact: Celina Erfle
• Phone: +49617260993208
• Email: celina.erfle[@]fmc-ag.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 192
• Est. completion date: March 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COPD Exacerbation

Intervention

Device:
• Extracorporeal carbon dioxide removal
Patients with acute exacerbation of severe COPD, requiring invasive mechanical ventilation will be treated with vv-ECCO2R to facilitate early extubation

Other:
• Conventional Care
Patient with acute exacerbation of severe COPD, requiring invasive mechanical ventilation treated with Conventional Care. Conventional care includes invasive mechanical ventilation and the attempt to extubate the patient and switch to NIV. If extubation fails tracheostomy can be performed according to the treating physician.

Locations

Country	Name	City	State
Germany	Kliniken der Stadt Köln gGmbH, ARDS and ECMO Zentrum Köln-Merheim	Köln

Sponsors (2)

Lead Sponsor	Collaborator
Xenios AG	Winicker Norimed GmbH

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death or severe disability	Death or severe disability at day 60 after randomization, with severe disability defined as confinement to bed and/or inability to wash or dress alone and/or need for long-term invasive mechanical ventilation by day 60	day 60
Secondary	Mortality or severe disability at day 180 after randomization	Change in mortality/severe disability rate	Day 180
Secondary	Ventilator-associated pneumonia during ICU treatment	Some sign of respiratory distress, e.g., increased RR, increased FiO2; New or enlarging infiltrates on CXR; Culture of relevant organism from lung or major change in secretions from lung	up to 60 days
Secondary	Reintubation rate	Number of reintubations	until day 180 after randomization
Secondary	Days on IMV or noninvasive ventilation (NIV) or ECCO2R	defined as duration of total ventilatory support	up to 60 days
Secondary	Thrombosis during treatment period	Thrombosis of major venous vessels during the treatment period	up to 29 Days
Secondary	Quality of life of patient	Measured at day 60 and 180 after randomization, measured with Severe Respiratory Insufficiency and EQ-5D-5L Questionnaire	up to 180 days
Secondary	Renal function	Worsening of renal function	up to 29 days
Secondary	Mobility, measured with ActiGraph	Subgroup: Activity measurement with ActiGraph (at 1 centre)	up to 180 days
Secondary	Treatment Cost	Total Treatment costs for the hospital stay	up to 180 days
Secondary	Length of hospital stay	Change in days of hospital stay	Up to 180 Days
Secondary	Need of tracheostomy	Change in rate of tracheostomy	Up to 180 Days
Secondary	Breathing	Breathing through tracheostomy at day 60 after randomization	up to 60 days
Secondary	Readmission	Readmission to hospital within 180 days after randomization	Up to 180 Days
Secondary	Exacerbations	Number of exacerbations within 180 days after randomization	Up to 180 Days
Secondary	Severe Bleeding	Defined as any bleeding event requiring administration of 1 unit of packed red cells, Detection of severe bleeding	up to 60 days