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

• ClinicalTrials.gov Identifier: NCT03584295
• Recruitment Status: Not yet recruiting
• First Posted: July 12, 2018
• Last Update Posted: August 2, 2022
• Sponsor: Xenios AG
• Information provided by (Responsible Party): Fresenius Medical Care Deutschland GmbH ( Xenios AG )

Tracking Information

• First Submitted Date: June 25, 2018
• First Posted Date: July 12, 2018
• Last Update Posted Date: August 2, 2022
• Estimated Study Start Date: September 2022
• Estimated Primary Completion Date: September 1, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 10, 2020)

Death or severe disability [ Time Frame: day 60 ]

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

Original Primary Outcome Measures (submitted: July 10, 2018)

Death or severe disability [ Time Frame: day 60 ]

Death or severe disability at day 60 after randomization. Severe disability is defined as confinement to bed and/or inability to wash or dress alone and/or need for long-term invasive mechanical ventilation.

Current Secondary Outcome Measures (submitted: December 10, 2020)

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

Original Secondary Outcome Measures (submitted: July 10, 2018)

• 1-year mortality or severe disability [ Time Frame: 1 year ]
  Change in mortality/severe disability rate
• Pneumonia during ICU treatment [ Time Frame: up to 60 days ]
  Change in Pneumonia rate
• Days on IMV/ Time on extracorporeal life support (=duration of support) [ Time Frame: up to 60 days ]
  Change in days on IMV/Time on extracorporeal life support
• Quality of life at 60 and 360 days (EQ-5D) [ Time Frame: 60 days and 360 days ]
  Change in Quality of life index
• Mobility, measured with ActiGraph [ Time Frame: up to 60 days ]
  Change in activity per day
• Treatment costs [ Time Frame: up to 60 days ]
  Change in absolute treatment costs
• Length of hospital stay [ Time Frame: up to 60 days ]
  Change in days of hospital stay
• Need for tracheostomy [ Time Frame: up to 60 days ]
  Change in rate of tracheostomy
• Reintubation rate [ Time Frame: up to 60 days ]
  Change in Reintubation rate

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Early Extubation by ECCO2R Compared to IMV in Patients With Severe Acute Exacerbation of 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)
• Brief 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.

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
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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.

Study Arms

• 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.
  Intervention: Other: Conventional Care
• 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.
  Intervention: Device: Extracorporeal carbon dioxide removal

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: December 10, 2020): 192
• Original Estimated Enrollment (submitted: July 10, 2018): 202
• Estimated Study Completion Date: December 31, 2025
• Estimated Primary Completion Date: September 1, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Anja Derlet-Savoia, Dr; +49 6172 608 2801; Anja.Derlet@fmc-ag.com

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT03584295
• Other Study ID Numbers: COPD-ECCO2R-01-INT
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Fresenius Medical Care Deutschland GmbH ( Xenios AG )
• Original Responsible Party: University of Witten/Herdecke
• Current Study Sponsor: Xenios AG
• Original Study Sponsor: University of Witten/Herdecke
• Collaborators: Not Provided

Investigators

• Principal Investigator: Christian Karagiannidis, M.D, Prof. Dr.; University of Witten/Herdecke

• PRS Account: Fresenius Medical Care Deutschland GmbH
• Verification Date: August 2022