Early Extubation by ECCO2R Compared to IMV in Patients With Severe Acute Exacerbation of COPD (X-COPD)

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)

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.

Study Overview

• Status: Recruiting
• Conditions: COPD Exacerbation
• Intervention / Treatment: Other: Conventional Care; Device: Extracorporeal carbon dioxide removal

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 192
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Celina Erfle; Phone Number: +49617260993208; Email: celina.erfle@fmc-ag.com

Study Locations

• Germany
  • Köln, Germany, 51109
    • Recruiting
    • Kliniken der Stadt Köln gGmbH, ARDS and ECMO Zentrum Köln-Merheim
    • Contact: Christian Karagiannidis, Prof. Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional care; Patients 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.	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.
Experimental: Extracorporeal carbon dioxide removal; Patients with acute exacerbation of severe COPD, requiring invasive mechanical ventilation will be treated with vv-ECCO2R (Extracorporeal carbon dioxide removal) to facilitate early extubation. 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.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality or severe disability at day 180 after randomization	Change in mortality/severe disability rate	Day 180
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
Reintubation rate	Number of reintubations	until day 180 after randomization
Days on IMV or noninvasive ventilation (NIV) or ECCO2R	defined as duration of total ventilatory support	up to 60 days
Thrombosis during treatment period	Thrombosis of major venous vessels during the treatment period	up to 29 Days
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
Renal function	Worsening of renal function	up to 29 days
Mobility, measured with ActiGraph	Subgroup: Activity measurement with ActiGraph (at 1 centre)	up to 180 days
Treatment Cost	Total Treatment costs for the hospital stay	up to 180 days
Length of hospital stay	Change in days of hospital stay	Up to 180 Days
Need of tracheostomy	Change in rate of tracheostomy	Up to 180 Days
Breathing	Breathing through tracheostomy at day 60 after randomization	up to 60 days
Readmission	Readmission to hospital within 180 days after randomization	Up to 180 Days
Exacerbations	Number of exacerbations within 180 days after randomization	Up to 180 Days
Severe Bleeding	Defined as any bleeding event requiring administration of 1 unit of packed red cells, Detection of severe bleeding	up to 60 days

Collaborators and Investigators

• Sponsor: Xenios AG
• Collaborators: Winicker Norimed GmbH
• Investigators: Principal Investigator: Christian Karagiannidis, Prof. Dr., Kliniken der Stadt Köln gGmbH, ARDS and ECMO Zentrum Köln-Merheim

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: June 25, 2018
• First Submitted That Met QC Criteria: July 10, 2018
• First Posted (Actual): July 12, 2018

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: COPD-ECCO2R-01-INT

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No