ECCO2R as an Adjunct to NIV in AECOPD

Extra-corporeal CO2 Removal as an Adjunct to Non-Invasive Ventilation in Acute Severe Exacerbations of COPD

Chronic obstructive pulmonary disease (COPD) is one of the UKs commonest chronic diseases and is responsible for a significant number of acute hospital admissions. COPD is characterised by progressive destruction in the elastic tissue within the lung, causing respiratory failure. The clinical course of COPD is characterised by recurrent acute exacerbations (AECOPD), causing considerable morbidity and mortality. Patients with moderate to severe acute exacerbations present with increased work of breathing and hypercapnia. The standard for respiratory support in this setting is non-invasive ventilation (NIV), a management strategy underpinned by a considerable evidence base. However despite NIV, up to 30% of patients with AECOPD will 'fail' and require intubation and mechanical ventilation. The mortality rate for patients requiring NIV is approximately 4%, if conversion to mechanical ventilation occurs the mortality is 29%.

The last decade has seen an increasing interest in the provision of extracorporeal support for respiratory failure. The key element that has underpinned improving survival has been technological advancement. This has resulted in pumps causing less blood trauma and inflammatory response, better percutaneous cannulation techniques and coated circuits with reduced heparin requirements. Overall this has significantly reduced the complications associated with the provision of extracorporeal support. One variation of this technique (extra-corporeal CO2 removal ECCO2R) allows CO2 clearance from the blood. This approach has been the subject of a number of animal experiments and uncontrolled human case series demonstrating improved arterial CO2 and reduced work of breathing. Our own unpublished series demonstrates the same physiological changes. However to date the benefits of this approach have not been tested in a randomised controlled trial.

The hypothesis is that the addition of ECCO2R to NIV will shorten the duration of NIV and reduce likelihood of intubation.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Device: NIV; Device: ECCO2R

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 7EH
    • Guy's and St Thomas' NHS Foundation Trust

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria

• Known COPD with an acute exacerbation. An acute exacerbation is defined as per the GOLD criteria as an increase in dyspnoea, cough and/or sputum over the patient's normal symptoms. A severe exacerbation is defined as one requiring hospital admission.
• Patients with a persistent arterial pH<7.30 due primarily to hypercapnic respiratory failure after standard medical therapy and at least 1 hour of NIV.
• Age over 18

Exclusion Criteria

• Haemodynamic instability after ensuring euvolaemia
• Acute multiple organ failure requiring other organ supportive therapy, including indication for intubation and mechanical ventilation
• Known allergy/intolerance of heparin including known heparin induced thrombosis and thrombocytopaenia
• Acute uncontrolled haemorrhage
• Intracerebral haemorrhage
• Recent (<6 months) ischaemic cerebrovascular accident
• Organ transplant recipient
• Expected to die within 24 hours
• Venous abnormality or body habitus precluding cannulation

• Contraindication to NIV (as per British Thoracic Society recommendation)

  • Facial burns/trauma/recent facial or upper airway surgery
  • Vomiting
  • Fixed upper airway obstruction
  • Undrained pneumothorax
  • Recent upper gastrointestinal surgery
  • Inability to protect the airway
  • Life threatening hypoxaemia (PaO2/FiO2 <20kPa)
  • Bowel obstruction
  • Patient refusal
• Pregnancy
• Severe hepatic failure (ascites, hepatic encephalopathy or bilirubin >100umol/L)
• Severe chronic cardiac failure (NYHA class III or IV)
• Bleeding diathesis (INR>1.5, platelets <80,000) in the absence of anticoagulation therapy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NIV; Standard application of NIV in hypercapnic respiratory failure as per usual standard of care	Device: NIV; Standard care
Experimental: ECCO2R; Addition of ECCO2R to NIV in AECOPD	Device: NIV; Standard care; Device: ECCO2R; Application of ECCO2R in addition to NIV; Other Names: Haemolung

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to cessation NIV	Time to cessation of NIV is defined as from NIV commencement to 6 hours without NIV.	participants will be followed for the duration of ICU stay, an expected average of 4 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality		at 90 days
Time to event analysis	This is a composite endpoint to assess the ability to complete the required elements of the study from screening to commencement of ECCO2R in a clinically relevant timeframe	initial phase of study, an expected average of 3 hours
Health-related quality of life (HRQoL)		90 days
Cannulation-related outcomes	composite outcome of cannulation related complications	participants will be followed for the duration of ICU stay, an expected average of 4 days
haemolysis related to the intervention		participants will be followed for the duration of ICU stay, an expected average of 4 days
work of breathing		participants will be followed for the duration of ICU stay, an expected average of 4 days
Time to cessation ECCO2R	Defined as from the commencement of ECCO2R to 6 hours following cessation of CO2 removal	participants will be followed for the duration of ICU stay, an expected average of 4 days
Time to normalisation of pH		participants will be followed for the duration of ICU stay, an expected average of 4 days
Hospital Length of stay		participants will be followed for the duration of hospital stay, an expected average of 10 days
Intubation rate		participants will be followed for the duration of ICU stay, an expected average of 4 days
Incidence of tracheostomy		participants will be followed for the duration of ICU stay, an expected average of 4 days
length of ICU stay		participants will be followed for the duration of ICU stay, an expected average of 4 days
Tolerance of therapy		participants will be followed for the duration of ICU stay, an expected average of 4 days
subjective dyspnoea		participants will be followed for the duration of ICU stay, an expected average of 4 days
nutrition	total caloric intake during interventional period	participants will be followed for the duration of ICU stay, an expected average of 4 days
Mobilisation	mobilisation from bed during the study period	participants will be followed for the duration of ICU stay, an expected average of 4 days
thrombotic complications	measurement of thrombotic complications in the patient related to the device	participants will be followed for the duration of ICU stay, an expected average of 4 days
respiratory mechanics		participants will be followed for the duration of ICU stay, an expected average of 4 days

Collaborators and Investigators

• Sponsor: Guy's and St Thomas' NHS Foundation Trust
• Collaborators: Alung Technologies
• Investigators: Principal Investigator: Nicholas Barrett, FCICM, Guy's and St Thomas' NHS Foundation Trust; Principal Investigator: Luigi Camporota, PhD, Guy's and St Thomas' NHS Foundation Trust; Principal Investigator: Nicholas Hart, PhD, Guy's and St Thomas' NHS Foundation Trust

Publications and helpful links

General Publications

• Barrett NA, Hart N, Daly KJR, Marotti M, Kostakou E, Carlin C, Lua S, Singh S, Bentley A, Douiri A, Camporota L. A randomised controlled trial of non-invasive ventilation compared with extracorporeal carbon dioxide removal for acute hypercapnic exacerbations of chronic obstructive pulmonary disease. Ann Intensive Care. 2022 Apr 21;12(1):36. doi: 10.1186/s13613-022-01006-8.
• Barrett NA, Hart N, Camporota L. In vivo carbon dioxide clearance of a low-flow extracorporeal carbon dioxide removal circuit in patients with acute exacerbations of chronic obstructive pulmonary disease. Perfusion. 2020 Jul;35(5):436-441. doi: 10.1177/0267659119896531. Epub 2020 Jan 11.
• Barrett NA, Kostakou E, Hart N, Douiri A, Camporota L. Extracorporeal carbon dioxide removal for acute hypercapnic exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial. Trials. 2019 Jul 30;20(1):465. doi: 10.1186/s13063-019-3548-4.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: March 9, 2014
• First Submitted That Met QC Criteria: March 12, 2014
• First Posted (Estimate): March 13, 2014

Study Record Updates

• Last Update Posted (Actual): August 11, 2021
• Last Update Submitted That Met QC Criteria: August 4, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: AECOPD; NIV; Non invasive ventilation; ECCO2R; Acute Exacerbation Chronic Obstructive Pulmonary Disease; Extracorporeal carbon dioxide removal
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: ECCO2R in AECOPD